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Synthesis and chemistry of alkyl 2, 3-bis(trimethylstannyl)-2-alkenoates and related substances Skerlj, Renato Tony 1988

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SYNTHESIS AND CHEMISTRY OF ALKYL  2,3-BIS(TRIMETHYLSTANNYL)-  2-ALKENOATES AND RELATED SUBSTANCES  By RENATO TONY SKERLJ B.Sc.  (Hons.), University o f Otago, New Zealand, 1982  A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE STUDIES DEPARTMENT OF CHEMISTRY  We accept this thesis as conforming to the required standard  THE UNIVERSITY OF BRITISH COLUMBIA January 1988 ©  Renato Tony S k e r l j , 1988  In  presenting  degree at the  this  thesis in  partial  fulfilment  of  the  requirements  for  an advanced  University of British Columbia, I agree that the Library shall make it  freely available for reference and study. I further agree that permission for extensive copying of  this thesis for  department  or  publication  by  his  or  scholarly purposes may be granted by the her  It  is  understood  that  my  copying  or  of this thesis for financial gain shall not be allowed without my written  permission.  Department The University of British Columbia 1956 Main Mall Vancouver, Canada V6T 1Y3  DE-6G/81)  representatives.  head of  ii  ABSTRACT  This  thesis  describes  the s y n t h e s i s and c h e m i s t r y o f a l k y l  bis(trimethylstannyl)-2-alkenoates these for  compounds  ((78)  and ( 8 3 ) ) .  It  was  c o u l d be r e a d i l y t r a n s f o r m e d i n t o u s e f u l  shown  The  tetrasub-  and t r i c y c l i c d i e n e s o f g e n e r a l s t r u c t u r e  synthesis  and c h e m i s t r y o f compounds (277)  that  intermediates  the s y n t h e s i s o f f u n c t i o n a l i z e d , s t e r e o c h e m i c a l l y d e f i n e d  s t i t u t e d a l k e n e s (87)  2,3-  (322A).  and (278)  is also  described. The variety  palladium(O)-catalyzed of  manner,  a,^-acetylenic  the  alkenoates  (90),  alkyl  of  hexamethylditin  to  afforded in a stereoselective (Z)-2,3-bis(trimethylstannyl)-2-  (E)-2 , 3 - b i s ( t r i m e t h y l s t a n n y l ) - 2 - a l k e n o a t e s  was f o u n d t h a t treatment o f  methylstannyl)-2-alkenoates  with  alkyl  (E)-  methyllithium  and  (78).  (Z)-2,3-bis(tri-  at  low  temperature,  f o l l o w e d by r e a c t i o n o f the r e s u l t a n t n u c l e o p h i l i c i n t e r m e d i a t e variety (80).  a  On the o t h e r h a n d , s u c c e s s i v e treatment o f m e t h y l w - h a l o - 2 , 3 - b i s -  provided a f a c i l e route  to  (202)  cyclic  with  methyllithium  /J-trimethylstannyl  and  HMPA  a,^-unsaturated  (203). Compounds  general structure from  with  o f a l k y l a t i n g a g e n t s , a f f o r d e d the t r i s u b s t i t u t e d v i n y l s t a n n a n e s  (trimethylstannyl)-2-alkenoates  esters  a  Subsequent t h e r m o l y s i s o f t h e s e compounds a f f o r d e d the  corresponding a l k y l It  esters  corresponding  (83).  addition  the  (80) (219)  were  i n which W i s  CO2R' m o i e t y .  intermediates  for  the  readily  These  synthesis  converted a  latter of  into  vinyl  functionalized compounds  functionalized,  iodides of  group  served  as  derived useful  stereochemically  iii  defined  tetrasubstituted  compounds (219) with  1.1  alkenes  (87).  or 2.2  equiv  For example,  treatment o f  o f n-butyllithium  a t -78*C  afforded the corresponding v i n y l l i t h i u m species (86) , which could e i t h e r be a l k y l a t e d d i r e c t l y or further (263A)  reagent  and then  transposed  alkylated,  into  to a f f o r d  the organocopper(I) i n each  case, the  t e t r a s u b s t i t u t e d alkenes (87). The (276)  Pd(0)-catalyzed addition of  to a v a r i e t y  o f a,B-acetylenic  tri-n-butylstannyltrimethylgermane esters (90) afforded the corre-  sponding compounds (277) and (278) i n a r a t i o respectively.  o f approximately  Treatment o f the (£) isomers (277) with n-butyllithium at  -98°C, followed by a l k y l a t i o n o f the resultant n u c l e o p h i l i c afforded  intermediate  the corresponding t r i s u b s t i t u t e d vinylgermanes (293).  these l a t t e r compounds was r e a d i l y (308),  3:1,  converted  into  the iodo  One o f bromide  which i s p o t e n t i a l l y s y n t h e t i c a l l y equivalent to the d,a synthon  (310). When the enolate anion o f compounds (203) was successively treated with  HMPA and compound (308) the esters (311) were obtained.  catalyzed intramolecular moieties (312). with  coupling  The Pd(0)  of the vinylstannane-vinyl  iodide  o f (311) provided a f a c i l e route to the b i c y c l i c t r i e n e esters S i m i l a r l y , a l k y l a t i o n o f the enolate anion  (325)  (which  was r e a d i l y  followed by the Pd(0)-catalyzed  o f compounds  (203)  obtained from (203), i n which n - 1),  coupling  o f the r e s u l t i n g  material afforded the t r i c y c l i c diene esters (322A).  alkylated  iv Me Sn  SnMe  3  H  •C0 R* 2  R  90  2  H  C0 R'  R  2  SnMe  3  2  H R  Me Sn  3  C0 Me  3  2  2  80  203  202  I.  W  E'  R  E  R  W  LI  >H 87 E  R  219  W  86  R  E  W  X  E  263A  2  Bu Sn  GeMe  3  ^ — ^ R  6  2  C0 R'  3  3  Me SCu  )H  Me Ge Q-Bu SnGeMe,  3  ^ — ^ SnBu  R  3  277  Me Ge  3  C0 Me  E  7  SnMe  78  Me Sn  C0 R'  3  2  C0 R'  3  83  Me Sn  H  Me Sn  3  C0 R' 2  278  C0 Et  3  2  H  Me  E 293  MeO,C Me SnMej I 311  or  Br  325  308 C0 Me 2  322A 310  V  TABLE OF CONTENTS  Page  ABSTRACT  ii  TABLE OF CONTENTS  v  LIST OF TABLES  viii  LIST OF FIGURES  ix  ABBREVIATIONS  x  ACKNOWLEDGEMENTS  xii  INTRODUCTION  1  I.  General  1  (a)  Transmetalation  2  (b)  Palladium(O)-catalyzed cross-coupling  II.  13  P r e v i o u s work and p r o p o s a l s  RESULTS AND DISCUSSION  28  I.  P r e p a r a t i o n o f a,B-acetylenic  II.  S y n t h e s i s o f a l k y l ( Z ) - and ( E ) - 2 , 3 - b i s ( t r i m e t h y l s t a n n y l ) - 2 - a l k e n o a t e s and ( E ) - ( N ) , ( N ) dimethyl-2,3-bis(trimethylstannyl)-2-alkenamides A.  B.  esters  28  . . .  33  P r e p a r a t i o n o f a l k y l ( Z ) - and (E)-2,3bis(trimethylstannyl)-2-alkenoates  33  S p e c t r a l d a t a o f a l k y l ( Z ) - and ( E ) - 2 , 3 bis(trimethylstannyl)-2-alkenoates  51  vi C. III.  66  Chemistry of a l k y l (Z) - and ( E ) - 2 , 3 - b i s (trimethylstannyl)-2-alkenoates A.  B. C. IV.  Preparation of (E)-(N),(N)-2,3bis(trimethylstannyl)-2-alkenamides  71  Transmetalation of the t i t l e compounds and reaction of the resultant intermediates with electrophiles  71  Synthesis of stereochemically t r i s u b s t i t u t e d v i n y l iodides  84  defined  Synthesis of functionalized stereochemically defined tetrasubstituted alkenes  109  Synthesis and chemistry of a l k y l ( E ) - 2 - ( t r i n-butylstannyl )- 3 -trimethylgermyl- 2 -alkenoates and a l k y l ( Z ) - 3 - ( t r i - n - b u t y l s t a n n y l ) - 2 - t r i m e t h y l germyl- 2 -alkenoates  123  A.  Synthesis of the t i t l e compounds  123  B.  Spectral data of a l k y l ( E ) - 2 - ( t r i - n - b u t y l stannyl) -2-trimethylgermyl-2-alkenoates and alkyl (Z)-3-(tri-n-butylstannyl)-2-trimethylgermyl-2-alkenoates  137  C  Chemistry of ethyl  (E)-2-(tri-n-butylstannyl)-  3-trimethylgermyl-2-butenoate V.  Synthesis of b i c y c l i c and t r i c y c l i c r i n g systems  VI.  Miscellaneous  143 . . .  152 164  EXPERIMENTAL I.  General  166  II.  Solvents and Reagents  168  III.  Preparation of cr./S-acetylenic esters  169  IV.  Synthesis of a l k y l (Z)- and ( E ) - 2 , 3 - b i s ( t r i methylstannyl) -2-alkenoates and (E)-N,N-dimethyl2,3-bis(trimethylstannyl)-2-alkenamides  186  Chemistry of a l k y l (Z)- and ( E ) - 2 , 3 - b i s ( t r i methylstannyl) -2-alkenoates  219  V.  vii  VI.  VII.  VIII.  IX.  REFERENCES  Synthesis of stereochemically defined substituted v i n y l iodides  tri-  Synthesis of stereochemically defined s u b s t i t u t e d alkenes  tetra-  241  259  S y n t h e s i s and c h e m i s t r y o f a l k y l (E)-2-(tri-nb u t y l s t a n n y l ) - 3 - t r i m e t h y l g e r m y l - 2 - a l k e n o a t e s and alkyl (Z)-3-(tri-n-butylstannyl)-2-trimethyl germyl-2-alkenoates S y n t h e s i s o f t r i c y c l i c and b i c y c l i c r i n g systems  276 .  .  .  299  318  viii LIST OF TABLES Table I.  II.  III.  IV.  V.  VI. VII.  VIII.  IX.  X.  XI.  XII.  XIII.  XIV.  Page C o n v e r s i o n o f a,^-acetylenic e s t e r s (90) i n t o a l k y l (Z)-2,3-bis(trimethylstannyl)-2-alkenoates (83) . . .  37  Conversion o f a l k y l ( Z ) - 2 , 3 - b i s ( t r i m e t h y l s t a n n y l ) - 2 - a l k e n o a t e s (83) i n t o a l k y l ( E ) - 2 , 3 b i s ( t r i m e t h y l s t a n n y l ) - 2 - a l k e n o a t e s (78)  46  Selected nmr c h e m i c a l s h i f t d a t a f o r compounds (78) and (83)  53  S e l e c t e d ^ C nmr c h e m i c a l s h i f t d a t a f o r compounds (78) and (83)  57  S e l e c t e d ^ C nmr J v a l u e s f o r compounds (78) and (83)  59  S n nmr d a t a f o r compounds (78) and (83)  64  Conversion of a,B-acetylenic N,N-dimethylamides (169) i n t o ( E ) - ( N ) , ( N ) - 2 , 3 - b i s ( t r i m e t h y l s t a n n y l ) - 2 - a l k e n a m i d e s (170)  70  Transmetalation of a l k y l (Z)- or ( E ) - 2 , 3 - b i s ( t r i m e t h y l s t a n n y l ) - 2 - a l k e n o a t e s ((183) o r (78)) and r e a c t i o n s o f the r e s u l t a n t i n t e r m e d i a t e s w i t h electrophiles  74  F o r m a t i o n o f c y c l i c B-trimethylstannyl u n s a t u r a t e d e s t e r s (203)  83  1 1 9  a,B-  P r e p a r a t i o n o f v i n y l l i t h i u m s p e c i e s and t h e i r reactions with electrophiles  112  P r e p a r a t i o n o f v i n y l c o p p e r ( I ) s p e c i e s and t h e i r reactions with e l e c t r o p h i l e s  118  Synthesis o f a l k y l (E)-2-(tri-n-butylstannyl)3 - t r i m e t h y l g e r m y l - 2 - a l k e n o a t e s (277) and a l k y l (Z)-3-(tri-n-butylstannyl)-2-trimethylgermyl-2a l k e n o a t e s (278)  131  Selected (278)  nmr d a t a f o r compounds (277) and  Transmetalation of ethyl ( E ) - 2 - ( t r i - n - b u t y l s t a n n y l ) - 3 - t r i m e t h y l g e r m y l - 2 - b u t e n o a t e (279) and r e a c t i o n s o f the r e s u l t a n t i n t e r m e d i a t e w i t h electrophiles  138  146  ix  LIST OF FIGURES  Figure  Page  1  The 400 MHz *H nmr spectrum o f  (137)  54  2  The 400 MHz *H nmr spectrum o f  (146)  54  3  The 75.6  MHz  1 3  C nmr and APT s p e c t r a o f  (141)  . . . .  61  4  The 75.6  MHz  1 3  C nmr and APT s p e c t r a o f  (158)  . . . .  62  5  The 111.8  MHz  1 1 9  S n nmr spectrum o f  (141)  65  6  The 111.8  MHz  1 1 9  S n nmr spectrum o f  (158)  65  7  The 400 MHz U  8  The 400 MHz  9  nmr spectrum o f  (221)  93  H nmr spectrum o f  (258)  114  The 400 MHz H nmr spectrum o f  (268)  120  l  X  X  10  The 75.6  MHz  1 3  C nmr and APT s p e c t r a o f  (285)  . . . .  141  11  The 75.6  MHz  1 3  C nmr and APT s p e c t r a o f  (286)  . . . .  142  X  LIST OF ABBREVIATIONS  Ac  -  acetyl  AIBN  -  azobisisobutyronitrile  APT  -  attached proton t e s t  br  -  broad  Bu  -  n-butyl  Biit  -  tert-butyl  d  -  doublet  DIBAL  -  diisobutylaluminum hydride  DME  -  1,2-dime thoxye thane  DMF  -  dimethylformamide  DMSO  -  dimethylsulfoxide  equiv/eq-  equivalent(s)  Et  -  ethyl  g  -  gram(s)  glc  -  g a s - l i q u i d chromatography  h  -  hour  HMPA  -  hexamethylphosphoric  ir  -  infrared  LDA  -  l i t h i u m diisopropylamide  Me  -  methyl  m  -  multiplet  mg  -  milligram(s)  MEM  -  methoxyethoxymethy1  min  -  minute(s)  triamide  xi  MOM  -  methoxymethyl  mp  -  melting point  mmol  -  millimole(s)  ms  -  mass s p e c t r a  Ms  -  methanesulfonyl  nmr  -  n u c l e a r magnetic  nOe  -  n u c l e a r Overhauser  PCC  -  p y r i d i n i u m chlorochromate  Ph  -  phenyl  PhH  -  benzene  Pr  -  isopropyl  q  -  quartet  s  -  singlet  t  -  triplet  TBDMS  -  tert-butyldimethylsiloxy  Tf  -  trifluoromethanesulfonyl  THF  -  tetrahydrofuran  THP  -  tetrahydropyranyl  tic  -  t h i n l a y e r chromatography  TMS  -  trimethylsilyl  Ts  -  jo- t o l u e n e s u l f o n y l  1  resonance enhancement  xii ACKNOWLEDGEMENTS  Firstly  I  would  like  to thank my research supervisor Professor  Edward Piers for his guidance and support throughout the course of these studies. Thanks are also extended to the various people associated with the 'group' for useful discussions during those times when things moving.  I would also l i k e to acknowledge the many people,  were  past and pre-  sent, for making my stay i n Vancouver an enjoyable experience. thanks  are  extended  not  Special  to CITR Radio for providing a breath of fresh a i r  during the time spent i n the lab. I would also l i k e to thank aspects  of  this thesis.  the  people  associated  of  this  Mrs.  The  proofread-  t h e s i s , Montse L l i n a s Brunet, Rick Friesen, Pierre Marais  and Miguel Angel Romero. finally  various  These people include the s t a f f of the nmr and  mass spectra labs for the recording of invaluable data. ers  with  Rani  Greg Statter  Theeparajah  for  the  use  of  his  for her prompt and e f f i c i e n t  PC,  and  typing of  this manuscript. F i n a n c i a l support from the Department of Chemistry i n the form a teaching assistantship i s  acknowledged.  Thank you and have a nice day.  of  xiii  Mojim R o d i t e l j i m a  Sta Tude Seres?  - 1 INTRODUCTION  I.  General  A fundamental stereoselective  goal  in  trialkylstannyl  use  alkenes  inherent  carbon-carbon  focused  upon  i n these compounds i s  that  '  affords  a  vinyllithium  i n t o an organocopper s p e c i e s which can  reaction  tolerates  alkenes  with  of The  bonds  Transmetalation^ with species  which  may  be  or f u r t h e r t r a n s p o s e d , then  be  organic  for  conjugatively  The p a l l a d i u m ( O ) - c a t a l y z e d c r o s s - c o u p l i n g  2)  trialkylstannyl  which  substituted  from o t h e r r o u t e s .  1)  example,  of  of  a great  f o r the f o r m a t i o n o f c a r b o n - c a r b o n  w i t h a wide v a r i e t y o f e l e c t r o p h i l e s  tion^'^  Recently,  and  they a l l o w the f o r m a t i o n  trapped  enones.  efficient  A particularly attractive  bonds i n a manner q u i t e d i f f e r e n t  an a l k y l l i t h i u m reagent  to  the  utility  be a c c o m p l i s h e d by two common r e a c t i o n s .  added  is  the  f o r such p u r p o s e s .  o f t r i a l k y l s t a n n y l alkenes  may  synthesis  c o n s t r u c t i o n o f c a r b o n - c a r b o n bonds.  d e a l o f a t t e n t i o n has been  feature  organic  reac-  electrophiles,  a wide v a r i e t y o f f u n c t i o n a l groups,  a  consti-  t u t e s a m i l d method o f forming new c a r b o n - c a r b o n bonds. Both o f these r e a c t i o n s vity.  This  feature  p r o c e e d w i t h a h i g h degree o f  satisfies  an important p r e r e q u i s i t e n e c e s s a r y  d e s i g n i n g an e f f i c i e n t  s y n t h e s i s o f a complex s u b s t r a t e  product).  vinylstannanes  synthetic  As  such,  organic chemists.  vinylstannanes  undergo,  c r o s s - c o u p l i n g are d i s c u s s e d  stereoselecti-  have  The two common transmetalation  become modes and  (e.g.  useful of  a  in  natural  'tools'  reactivity  for that  palladium(O)-catalyzed  i n more d e t a i l i n the f o l l o w i n g  sections.  - 2 -  (a)  Transmetalation  The  transmetalation  reaction,  y e a r s ago by S e y f e r t h , ' ^ i n v o l v e s 3  which a  was d i s c o v e r e d almost  metathesis  reaction  thirty  between  an  o r g a n o l i t h i u m s p e c i e s and an organostannane (or an o r g a n i c d e r i v a t i v e o f another  heavy m e t a l ) ( e q u a t i o n 1).  R SnR' 3  The  +  R"LI  R'Li  1  r e a c t i o n has been shown t o be r e v e r s i b l e ,  mixture  favouring  t h e more  stable  +  state^  (1).  Recent  studies  existence o f hypervalent implicated  them  as  proceed  Nevertheless,  through  have  a  provided  pentaorgano-tin  being intermediates  of  t h e r e a c t i o n has transition  evidence  'ate' complexes  (2)  i n the l i t h i u m - t i n  and  have  exchange.^  t o suggest  plexes  s p e c i e s , ^ since tests i n d i c a t e that  these  'ate' complexes  reagents  toward  n-butyl iodide.  reactive  are substantially  electrophiles  such  as  less  these  f o r the  However, t h e r e has been no evidence are the a c t u a l  that  Although  transmetalation  four-centred solid  (1)  equilibrium  o r g a n o l i t h i u m species.**  n o t y e t been s e c u r e l y e s t a b l i s h e d .  g e n e r a l l y been assumed t o  3  l e a d i n g t o an  k i n e t i c s t u d i e s have been undertaken, t h e mechanism has  R S n R"  reactive  trimethylsilyl  ' a t e ' com-  than  lithium  c h l o r i d e and  - 3 The transmetalation reaction i s a s y n t h e t i c a l l y v i a b l e process for a number of reasons. temperatures, cific.  1) The reaction usually proceeds e f f i c i e n t l y  below  -50 C.  2)  C  which  low  The reaction is completely stereospe-  3) The by-product of the reaction i s a coordinatively  compound  at  saturated  does not usually interfere with reactions of the  lithi-  ated product. In the case of vinylstannanes, tin-carbon  bond  which  allows  i t is the r e l a t i v e  transmetalation^  weakness  to occur.  of  the  This i s  in  stark contrast to vinylgermanes and v i n y l s i l a n e s which are unreactive to alkyllithium  reagents  due  to  the r e l a t i v e strength of the germanium-  carbon and s i l i c o n - c a r b o n bonds. clearly  9  This  difference  in  reactivity  is  exemplified by the synthesis of an intermediate for the Nazarov  cyclization  (equation  2).^  Thus,  transmetalation  of  (3)  with  3.Ni0 ,Et 0 2  2  n - b u t y l l i t h i u m at -78°C afforded the corresponding v i n y l l i t h i u m species, which was allowed to react with 3- or to  afford  the  corresponding  6-methyl-1-cyclohexenecarbaldehyde  alcohols.  Subsequent  oxidation of the  l a t t e r materials afforded the d i v i n y l ketones (4) which  underwent  the  Nazarov c y c l i z a t i o n to form the b i c y c l i c enones ( 5 ) . The  fact that v i n y l l i t h i u m reagents r e t a i n the configuration of the  organotin precursors  was  utilized  by  Corey^  in  the  synthesis  of  - 4 E  11-deoxyprostaglandin  (9)  2  (Scheme  1).  The v i n y l s t a n n a n e  r e a d i l y p r e p a r e d by the h y d r o s t a n n a t i o n o f the t e r m i n a l Transmetalation  of  (7)  resulting vinyllithium  with  n-butyllithium  and  conversion  by r e a c t i o n o f the l a t t e r s p e c i e s w i t h 2 - c y c l o p e n t e n - l - o n e ,  (8)  into  the p r o s t a g l a n d i n (9)  OTHP  (Scheme  sequence o f  (6).  of  the  followed  afforded  steps  the  converted  1).  Bu Sn 3  0-Bu,SnH  H-  A further  was  acetylene  species into a s u i t a b l e cuprate reagent,  conjugate a d d i t i o n product (8).  (7)  1.n-BuLI  AIBN  •OTHP  2  -Pr  =  Cu  3.  OTHP (CHahCOOH  (CH2)4 C H 3  OH  Scheme 1  An Still^  e l e g a n t use o f f u n c t i o n a l i z e d v i n y l s t a n n a n e s was demonstrated by i n the s y n t h e s i s o f  germacranolide  The  desired  (10)  by a sequence o f s t e p s shown i n Scheme 2.  with  cyclobutenyl  the  n-butyllithium  t i n reagent  afforded  the  (11)  eucannabinolide  was p r e p a r e d from the Transmetalation of  corresponding v i n y l l i t h i u m  (13). ketal (11)  species,  - 5which, upon treatment with the enone, formed (12) (12)  as  the major diastereomer.  the  1,2-addition  product  A further sequence of steps converted  into the natural product (13)  (Scheme 2).  Bu Sn 3  l.BujSnMgCI 0  M  e  2  1 0  K  2.MsCI 3.K C0 ,DMSO 3  OMe  11  Ln-BuLI  OMe  OMe  AcO OMe  R=PhCH OCH 2  2  Scheme 2  Vinylstannanes have also been shown to be the  synthesis  of  polyenes,  with  (Scheme 3 ) .  1 3  Thus,  for  transmetalation  of  1 equivalent of n-butyllithium, followed by treatment of the  r e s u l t i n g v i n y l l i t h i u m species with a suspension coupling  precursors  such as 12-hydroxyeicosa-5,8,14 (Z),10(E) -  tetraenoic a c i d (12-HETE) (18) (14)  valuable  of  the  of  n-Bu^NCu(CN)2  and  resultant reagent with a functionalized a l k y l iodide,  afforded the vinylstannane (15).  Sequential  treatment  of  (15)  with  - 6 n-butyllithium  and cuprous bromide•dimethylsulphide complex afforded an  organocopper reagent, The  resultant  which was treated with the acetylenic ketone  (16).  intermediate was quenched with a p r o t i c source to afford  the corresponding conjugate addition product (17). of steps converted (17)  into the polyene 12-HETE  A  further  sequence  (18).  4.HOAc,MeOH  Scheme 3  The  scope of the transmetalation reaction i s further i l l u s t r a t e d by  the stereocontrolled construction plasmomycin, reaction  of  vinyllithium  a (19)  boron-containing with  species,  cyanide and the epoxide  of  the  antibiotic  n-butyllithium which (20)  was  C(3)-C(17)  (equation  produced  sequentially  fragment  the treated  to afford the coupled product  3).^  of  a-  Thus,  corresponding with (21).  cuprous  - 7 Bu Sn 3  The retention of stereochemistry i n the stannanes  of  vinyl-  has been used i n the short synthesis of the marine metabolite  (±)-triophamine configuration product.  transmetalation  (25) of  the  (Scheme  4).  olefinic  This  1 5  double  Thus, transmetalation of  bonds  work  established  present  the  i n the natural  (E)-3-(tri-n-butylstannyl)-2-pentene  Scheme 4  - 8(22)  with  n-butyllithium,  followed  by  resultant v i n y l l i t h i u m species to (23), hydrazide  (24).  A  natural product (25) . repeated  further  conjugate  addition  of  the  provided the o l e f i n i c trimethyl-  sequence of steps converted (24)  into the  When a s i m i l a r sequence of steps (Scheme  with (Z)-3-(tri-n-butylstannyl)-2-pentene  4)  was  a material different  from the natural product was o b t a i n e d . ^ Recently a vinylstannane has been exploited for the synthesis of  of  (26)16^ with n-butyllithium chemoselectively  species,  which  derivative. the  a tetrasubstituted alkene (Scheme 5 ) . ^  was  transformed  into  the  a  stereoselective Thus,  afforded a  treatment  vinyllithium  corresponding organocopper  The l a t t e r species was coupled with a l l y l bromide  trisubstituted  vinylstannane (27).  afforded  the  vinyllithium  treatment  (28).  with  This  iodide to afford the tetrasubstituted alkene  (29).  Hex  1.n-BuLI 2.CuBr>Me S 3.CH CHCH Br 2  Et B  SnMe  2  3  2  SnMe  2  26  3  27 2.t-BuLi Hex  Me  Hex  1.CuBr>Me,S HMPA,P(OEt) 2.Mel  3  29 Scheme 5  LI 28  (27) tert-  reagent  converted into an organocopper derivative which was coupled with  Hex  form  Halogen-metal exchange of  gave the corresponding v i n y l iodide, which, upon butyllithium,  to  was  methyl  - 9 -  The vinylstannane (26) can be regarded as a b i f u n c t i o n a l conjunctive reagent.^  By d e f i n i t i o n ^ such a reagent possesses two reactive  (e.g.  donor  two  centres,  two  acceptor centres,  acceptor centre) and is incorporated i n whole or i n strate  molecule.  centre.^  synthon*  (30),  or one donor and one part  into  a  sub-  A donor (d) centre refers to a p o t e n t i a l n u c l e o p h i l i c  centre, whereas an acceptor (a) centre refers to philic  sites  Hence in  which  (26) the  is two  a  potential  electro-  s y n t h e t i c a l l y equivalent to the d,d donor  centres  are  cis-related.  Hex  The  versatility  of vinylstannanes has recently been highlighted by  the stereoselective synthesis of substituted enynes, dienes and via  the  stannylation  treatment of (31) with equiv)  in  of  1-trimethy1silyl  trimethylstannylcopper-dimethyl  were  (32)  sulfide^  stereoselective  fashion.  then further elaborated into stereodefined  tuted enynes (35). of  Thus, upon (2.5  THF the corresponding (E)-bis(trimethylstannyl) enynes (32)  were obtained i n a chemo- and materials  1,3-diynes.^  alkenes  Addition of 1 equiv of methyllithium to  i n THF afforded, chemoselectively,  These  latter  tetrasubstia  solution  the corresponding v i n y l l i t h -  ium species, which were trapped with an appropriate e l e c t r o p h i l e to form the  trisubstituted  vinylstannanes  (34).  A further sequence of steps  A synthon i s a u n i t within a molecule which can be synthesized, modified or joined by known or conceivable synthetic operations.^ 9  - 10 involving  transmetalation-alkylation  tuted enynes (35) (Scheme 6). equivalent  to  of (34) afforded the. t e t r a s u b s t i -  Compounds  (32) are  thus  synthetically  the d,d synthons (33) i n which the two donor centres are  trans-related.  Scheme 6  In the preceeding discussion, two examples conjunctive  reagents  possessing  two  donor  Attention now w i l l be focussed on examples of reagents  possessing  a  donor  portraying b i f u n c t i o n a l centres  bifunctional  reactions.^2  presented. conjunctive  carbon atom and an acceptor carbon atom.  Reagents corresponding to such synthons constitute annulation  were  of  for  reagents  w-substituted 2-trimethylstannyl-l-alkenes (37) can be r e a d i l y  prepared  by the addition of  precursors  species the  xhe  required  useful  trimethylstannylcopper'dimethyl sulfide to w-substi-  - 11 -  1-alkynes  4).2  The s u b s t a n c e s (37) a r e p o t e n t i a l l y  the  3  i n the presence o f methanol synthetically  (equation  equivalent  to  d,a synthons ( 3 8 ) .  _____ "  (36) a t  -63°C  tuted  = =  MejSnCu-MejS.tf eq) l*' 2)n  —  M  x  37  utility  of  compounds  of  e x e m p l i f i e d by the development  of  annulation  was  process^a  (±)-A ^ )-capnellene 9  12  which  •  •  \  36  The  d  <  MeOH(60 eq),-63°C  N  SnMe,  /  \ (  C  general an  H  2  )  n ~  (41 1  '  38  X  structure  (37) i s c l e a r l y  e f f i c i e n t methylenecyclopentane  used  i n the  total  synthesis  of  (42) (Scheme 7 ) . ^ Thus, t r a n s m e t a l a t i o n o f (39) 2  Scheme 7  - 12 afforded  the corresponding v i n y l l i t h i u m species, which was treated with  magnesium bromide to form the corresponding Grignard reagent. Copper(I)catalyzed addition of the l a t t e r reagent to 2-methyl-2-cyclopenten-1-one i n the presence of boron t r i f l u o r i d e addition  product (40).  etherate  which,  via  steps, was converted into ( ± ) - A ( 1 2 ) - c a p n e l l e n e 9  (46) tion  a  total  the  a  further  sequence  of  (42).  synthesis of the sesterterpenoid  (±)-palauolide  (Scheme 8)25 was achieved u t i l i z i n g a methylenecyclohexane process,^2b  conjugate  Treatment of (40) with potassium hydride i n THF  afforded the b i c y c l i c ketone (41),  Recently,  afforded  ambula-  which had been developed using reagents corresponding  Scheme 8  - 13 -  to  d,a  synthons  similar  to those d i s c u s s e d above.  sequence o f s t e p s e n t i r e l y analogous 7),  the  to those  discussed  (44).  Treatment  of  the l a t t e r  the  chloro  substance w i t h p o t a s s i u m  f u r t h e r sequence o f s t e p s , was c o n v e r t e d i n t o  tert-  ( 4 5 ) , which v i a a (46).^5  (±)-palauolide  Palladium(O') - c a t a l y z e d c r o s s - c o u p l i n g  One  o f the most v e r s a t i l e  y e a r s has been the organotin  reactions  reagents  taining Hg)^  of product.  metals  tolerates  of  Although  wide  variety  stereospecific  other  electrophiles,  organostannanes  organostannanes  relatively  easy  to  and  of  functional gives  reagents  character (e.g.  conZ n , B,  reactions  with  have been the most w i d e l y u s e d .  are p a r t i c u l a r l y  prepare  of  and g e n e r a l l y  organometallic  intermediate e l e c t r o p o s i t i v e  Presumably,  gen.  a  reaction  few  T h i s r e a c t i o n takes  undergo p a l l a d i u m ( O ) - c a t a l y z e d c r o s s - c o u p l i n g  D  organic  cross-coupling  with organic e l e c t r o p h i l e s . ^ • ^  groups on e i t h e r c o u p l i n g p a r t n e r , i s high yields  to have emerged i n the p a s t  palladium(O)-catalyzed  p l a c e under m i l d c o n d i t i o n s ,  Al,  (Scheme  (43) was added  to a f f o r d  b u t o x i d e i n t e r t - b u t a n o l . a f f o r d e d the b i c y c l i c ketone  (b)  following a  above  G r i g n a r d reagent d e r i v e d from the v i n y l s t a n n a n e  c o n j u g a t i v e l y to 3 , 6 - d i m e t h y l - 2 - c y c l o h e x e n - l - o n e , ketone  Thus,  are s t a b l e  useful  because  they  are  towards m o i s t u r e and oxy-  2 7 a  In the p a l l a d i u m ( O ) - c a t a l y z e d c r o s s - c o u p l i n g o f organotin  reagents,  coupling reaction  only (equation  one 5).  of  the  groups  Furthermore,  electrophiles  on t i n e n t e r s different  into  groups  with the are  - 14 -  RX  +  R"SnR'  "  3  R- R'  transferred from t i n with different rates.  For  +  XSnR'  example,  (5)  3  simple  alkyl  o  groups (e.g.  methyl or butyl) exhibit the slowest transfer rate.  Thus,  an unsymmetrical organotin reagent containing three simple a l k y l  groups  and  a  fourth functionalized group (e.g.  or a l l y l ) w i l l transfer, exclusively, Functionalized cross-coupling  vinylstannanes  reaction  2  triflates, ^  and  3  aryl  dium^) -catalyzed illustrated  a c  a  the  variety  halides.  The  3 2  palladium(O)-catalyzed  of  i d chlorides,  cross-coupling  2 9  electrophiles: allyl  pathway  reaction  is  electrophile  to  a  transmetalation, the  considered  to  be  thought  trans/cis coupled  isomerization  product  and  3 u  aryl  to  occur  is  The i n i t i a l step addition  of  the  The subsequent steps are reductive  elimination,  R-R' and the palladium complex 'PdT_2'.  The most commonly used palladium catalyst is phine)palladium(O)  oxidative  palladium complex 'PdL,2'.  halides,  vinyl  v i a which the p a l l a -  by the c a t a l y t i c cycle shown i n Scheme 9.  i n the reaction can be  affording  2 7  the l a t t e r group.  undergo  with  halides, ** v i n y l t r i f l a t e s ,  alkynyl, a l k e n y l , a r y l , benzyl  tetrakis(triphenylphos-  (Pd(PPh ) ). 3  4  The high s t e r e o s e l e c t i v i t y and the tolerance of functional groups i n the  cross-coupling  insect pheromone (49) stannane  (47)  pheromone (49).  was  reaction  is  illustrated  by  the synthesis of the  (equation 6 ) . ® Thus, i n a single step the v i n y l 2  coupled  with  the  v i n y l iodide (48)  This reaction proceeded without  any  to afford the  isomerization  of  the o l e f i n i c double bonds and without protection of the alcohol moiety.  - 15 -  Bu  47  48  49  The u t i l i t y of the palladium(O)-catalyzed cross-coupling reaction i s further i l l u s t r a t e d by the synthesis  of  the  synthesis  antibiotic  of  a  key  intermediate  ( ± ) - p y r e n o p h o r i n (53)  (Scheme 1 0 ) .  Thus, the a c i d chloride (50) was coupled with the vinylstannane afford  the  antibiotic  ketone (53).  (52),  which  was  in  the 2 9 a  (51)  >  3 3  to  subsequently elaborated into the  The coupling reaction proceeded i n the presence of the  ester group and with retention of double-bond configuration.  - 16 -  Scheme 10  A  further  example  groups can be tolerated Reaction  of  the  illustrating  that a wide v a r i e t y of  i n the coupling process is shown i n equation  functionalized  allyl  bromide  (54)  stannane (55) proceeded smoothly to afford the coupled In  functional  with  7.  the v i n y l  product  (56).  p a r t i c u l a r , this reaction exhibits regioselective carbon-carbon bond  formation since the a l l y l halide  (54) undergoes  substituted carbon of the a l l y l i c framework.  coupling  at  the  less  - 17 One  of  the more v e r s a t i l e coupling processes involves the reaction  of vinylstannanes with v i n y l t r i f l a t e s , be  since the l a t t e r substances  can  obtained r e a d i l y from ketones ^ i n a regioselective manner u t i l i z i n g 3  well known enolate chemistry. synthesis  transformation  strated  in  triflate  (58) was prepared as one regioisomer from  hexen-l-one  a  This type of  (57)  by  of p l e r a p l y s i l l i n - 1 (60)  conjugate  reduction  followed by trapping of the enolate with imide.  Palladium(O)-catalyzed  (Scheme l l ) .  demon2 7 b  The  5,5-dimethyl-2-cyclo-  utilizing  L-Selectride,®  N-phenyltrifluoromethylsulfon-  coupling of (58) with the vinylstannane  (59) proceeded smoothly i n the presence of lithium pleraplysillin-1  was  chloride  to  afford  (60).  Scheme 11  Recently,  an  annulation method leading to diene systems -* has been 3  developed u t i l i z i n g intramolecular of  enol triflate-vinylstannanes  palladium(O)-catalyzed  (equation 8).  cyclizations  For example, transforma-  - 18 -  n =  1  or  2  t i o n of the ketones (61) accomplished Treatment of  by  utilizing  compounds  effected e f f i c i e n t A  variant  into the corresponding enol t r i f l a t e s the  (62)  procedure  with  a  of  McMurry  catalytic  (62)  and  amount  Scott. ^ 3  of  (PPt^^Pd  r i n g closure to produce the b i c y c l i c dienes  of  the  was  (63).  annulation method described above that produces  products i n which both double bonds of the diene system  are  has been developed ** and applied to the t o t a l synthesis of  (±)-(14S)-  3  dolasta-l(15),7,9-trien-14-ol  (67)  (Scheme 1 2 ) .  endocyclic  Thus, the enolate of  3 6  the ketone (64) was formed under thermodynamically controlled conditions and  alkylated with (Z)-l-bromo-4-methyl-3-trimethylstannyl-2-pentene  afford the corresponding ketone (65). with  lithium  trapped with sponding  enol  diisopropylamide  The l a t t e r material  affording  Direct  addition  of  (PPlvj^Pd to the solution containing the l a t t e r ketal  diene  (66).  treated  the enolate anion, which was  N_-phenyltrifluoromethylsulfonimide triflate.  was  to  producing a  the  corre-  c a t a l y t i c amount of  material  provided  A further sequence of steps converted (66)  the  into the  - 19 -  Scheme 12  natural product ( ± ) - ( 6 7 ) . S t i l l e ^ recently demonstrated that the intramolecular 3  catalyzed  c y c l i z a t i o n s of v i n y l t r i f l a t e - v i n y l s t a n n a n e s can be used for  the synthesis of l a r g e - r i n g lactones  68 performed  palladium(O)-  under  (equation 9).  The  reactions  were  69 high  afford the lactones  (69)  d i l u t i o n (10"* M) conditions i n r e f l u x i n g THF to i n i s o l a t e d y i e l d s of 56-57%.  Under  the  mild  - 20 reaction  conditions,  no  E to Z isomerization of the E alkene function  and no rearrangement of the exocyclic double bond occurred. Although the chemical l i t e r a t u r e contains numerous trating  the  examples  u t i l i t y of the palladium(O)-catalyzed cross-coupling reac-  t i o n , the examples discussed i n the preceeding text serve to the  relative  illus-  ease  with  which  two  sp  2  illustrate  carbon centres can be brought  together with the formation of a new carbon-carbon bond.  I I . Previous work and proposals  Previous work i n our laboratories had focussed on various  (trimethylstannyl)copper(I)  esters. ^ 3  reagents  It was shown that the conjugate  reagents to a,3-acetylenic  esters (e.g.  the  reaction  with  addition  of  a,8-acetylenic  of  two  ethyl 2-butynoate)  of  (70)  these  could be  c o n t r o l l e d experimentally so as to produce, s t e r e o s e l e c t i v e l y , either of the  geometrically  control) or (72)  isomeric  products  (71)  (the  product  (the product of thermodynamic control)  C0 Et  Me  of  kinetic  (Scheme  IS). **  H  Me  2  3  + Me Sn  70  3  71  (Me SnCuSPh)LI , - 48°C,THF 2 Me SnCu»Me S , -48°C,THF > 99 3  3  2  Scheme 13  H  Me Sn 3  72  C0 Et 2  98  <1  3  - 21 Thus,  reaction  of  (70)  with  lithium  (phenylthio)(trimethylstannyl)-  cuprate (THF, - 4 8 ° C ) , followed by protonation, produced the (72)  (>98% isomerically pure).  isomer  On the other hand, reaction of (70) with  (trimethylstannyl)copper(I)•dimethylsulfide protonation, produced the (E) isomer (71) At  (Z)  (THF,  -48°C),  followed  by  (>99% isomerically pure).  the time the preceeding study was done i t was envisaged that the  synthetic u t i l i t y of the methodology described above could significantly  i f the presumed intermediates  trapped with electrophiles corresponding  ("E+")  other  products (75) and/or (76)  than  failed.  enhanced  and/or (74)  could be  proton  (Scheme 15).  to trap (73) and/or (74) with electrophiles bromide or cyclohexanone)  (73)  be  (e.g.  the  However, attempts benzyl  In each case, appropriate workup gave  C0 Et  3  afford  methyl iodide,  C0 Et  Me  Me Sn  to  2  Me Sn  Cu — |  3  2  73  E  Me  Me Sn 3  75  C0 Et  Me Sn  2  3  76  E  Scheme 15  The formulas (73) and (74) are not meant to imply actual structures, but are used for the sake of c l a r i t y .  - 22 -  only  the  efforts  product  r e s u l t i n g from protonation of the intermediates.  to f i n d conditions under which the  desired  trapping  would take place, the reaction temperature was increased. methyl iodide was added to the reaction (70)  to  mixture  reactions  However, when  obtained  by  workup  Instead, substance  contained  none  of  the  desired  product (76)  there was obtained, i n addition to (76) which  subsequently butenoate  contained  identified  two as  (E = CH3).  (E=H), a low y i e l d of a  trimethylstannyl ethyl  obtained  groups and which was  (E)-2,3-bis(trimethylstannyl)-2-  (77).  Compound  (77)  represented  a  novel  type of organotin d e r i v a t i v e .  After some experimentation i t was found that when (70) react  allowing  react with (trimethylstannyl)copper(I)•dimethylsulfide and the  temperature was allowed to r i s e from - 4 8 ° to 0 ° C , the material upon  In  (THF,  was  allowed  to  - 4 8 ° C , 30 min, 0 ° C , 3 h) with 2.5 equiv of (trimethylstan-  nyl) -dimethyl s u l f i d e ,  the ester ethyl  (E)-2,3-bis(trimethylstannyl)-2-  butenoate (77) was produced i n good y i e l d (equation 10).^1  Me Sr\  C0 Et  3  Me  —  C0 Et 2  M  » SnCu.Me S 2.5 eq, THF 3  2  /  70  2  \ = J \  (10)  77  Interestingly,  the ct-Me3Sn  stannyl)-2-butenoate  (77)  group  of  ethyl  (E)-2, 3-bis (trimethyl-  could be removed d i r e c t l y and s e l e c t i v e l y by  transmetalation with methyllithium, without interference from either the ester  moiety  or the B-tte^Sn group.  Furthermore, i t was found that the  resultant n u c l e o p h i l i c intermediate reacted with a v a r i e t y  of  reactive  - 23 electrophiles 11) . ^  to  afford  trisubstituted  vinylstannanes  (75)  (equation  It has been postulated that the intermediate r e s u l t i n g from  2  Me Sn  C0 Et  3  Me Sn  2  the  C0 Et  3  2  1 .MeLl.THF Me  SnMe  77  transmetalation  of  Me  3  an  E  75  a,/?-bis(trimethylstannyl)  such as (77) with methyllithium i s  an  allenoate  aunsaturated  ester  anion  which  reacts with an e l e c t r o p h i l e to give only one stereoisomer 12) .  In f a c t , M a r i n o ^ has reported evidence  allenoate  intermediate  may  be  involved  that  in  (79),  3 9  (80) (equation  indicates  the  that  an  addition of lithium  dimethylcuprate to methyl propynoate.  Me Srt  C0 R'  3  Me Sn  2  >=<  R  78  SnMe  R  3  One of our i n i t i a l goals preparing  alkyl  tive route. reasons.  was  79  to  2  R  investigate  for  a  In the previous synthesis of a l k y l  dimethyl s u l f i d e ,  C0 R'  3  OLI  An alternative was desirable 1)  Me Sn  80  the  2,3-bis(trimethylstannyl)-2-alkenoates  stannyl) -2-alkenoates  2.5  equivalents  and, therefore,  required to form 1 equivalent of This  OR'  3  of  (12)  E  possibility  of  v i a an alterna-  number  of  practical  (E)-2,3-bis(trimethyl-  (trimethylstannyl)copper(I)•  2.5 equivalents of hexamethylditin are the  desired  product  (equation  10).  i s an important point since the p r i c e of hexamethylditin i s >$3.00  per gram.  2) Copper(I) reagents are very sensitive to moisture,  oxygen  - 24 and  traces  of  inorganic  s a l t s , ^ and, therefore,  these reagents can be capricious. the  formation  of  bromide'dimethyl  sulfide,  after a short period of time.  these  reagents  CuBr.Me2S),  or,  methyllithium). are  3) The reagents that are required for  of (trimethylstannyl)copper(I)• dimethyl s u l f i d e , methyl-  l i t h i u m and copper(I) activity  reactions involving  are  taken  either from  unstable,  to  lose  prepared  (in  a freshly opened bottle^*  the (i  2  case  it  of  the case of  n  (trimethylstannyl)copper(I)  therefore,  their  Thus, i t i s important that both  freshly  Furthermore, the  thermally  tend  reagents  i s necessary to carry out the  reactions at low temperatures. Mitchell,^*  33  has reported the preparation of  stannyl)-1-alkenes  (82)  by a novel route.  (Z)-1,2-bis(trimethyl-  Treatment of 1-alkynes  with hexamethylditin i n the presence of a c a t a l y t i c amount of afforded  (82)  in  a stereoselective manner (equation  Me Sn •H  e  6  S  n  H  2  y  Pd(pph ) 3  81  4  ~  R  =  82  reaction  was  not  proceed for 1-alkynes to  extend  the  investigated  thoroughly,  (i3)  "  but  i n which R-Ph, MeOCH2 or PhCT^.  palladium(O)-catalyzed  addition  non-terminal acetylenes were not successful. i t would be worthwhile to investigate 2,3-bis(trimethylstannyl)-2-alkenoates of hexamethylditin to a,B-acetylenic  3  /  y i e l d s of (82) ranged from 29% (R-C4H9) to 80% (R-H). the  (PPh^^Pd  13).Isolated  SnMe  3  M  (81)  The generality of i t was found to However,  efforts  of hexamethylditin to  Nevertheless,  we f e l t  that  the p o s s i b i l i t y of preparing a l k y l by the esters.  Pd(0)-catalyzed  addition  - 25 In the general introduction, the two common types of vinylstannanes  undergo,  transmetalation  and  reaction  palladium(O)-catalyzed  cross-coupling, were shown to be highly v e r s a t i l e and depending particular  reaction,  were  selective.  Thus, i t was  shown  of  to  interest  to  chemistry of 2,3-bis(trimethylstannyl)-2-alkenoates  appeared  to  in  synthesis.  (Z)  defined tetrasubstituted alkenes  Thus, transmetalation isomer  (83) ,  would  of  either  presumably  the  (E)  afford  For  to (84)  example, (78),  a  it  respect-  functionalized, or (87),  isomer  the  intermediate (79) , which could be trapped with  the  to determine whether  i v e l y ) could serve as precursors for a f a c i l e route  16).  the  investigate  us that either the (Z) or (E) esters ((83),  stereochemically  on  be chemo-, regio- and/or stereo-  particular  or not they could be used e f f e c t i v e l y  that  (Scheme  (78)  or  same allenoate variety  of  the anion  electro-  philes to afford the corresponding t r i s u b s t i t u t e d vinylstannanes  (80).  Suitable manipulation of the ester group of (80) would provide compounds of general structure (85) moiety).  CO2R'  These  synthetic equivalents  (W i s a functionalized group derived from latter  of  the  compounds synthons  could  (88).  serve For  as  the  effective  example,  it  was  envisaged that reagents (86) , presumably available by transmetalation of (85),  could be trapped by a  corresponding  tetrasubstituted  substituted alkenes catalyzed  (84)  cross-coupling  organic e l e c t r o p h i l e flate).  If  variety  the  (e.g.  plans  could  of  alkenes be  reaction  electrophiles (87).  prepared of  to  afford  A l t e r n a t i v e l y , the f u l l y from  the  palladium(O)-  the vinylstannanes  vinyl halide,  allyl  halide  or  outlined i n Scheme 16 proved to be  then the synthesis of functionalized,  the  stereochemically  (85) with an vinyl  tri-  successful,  defined  tetra-  - 26 -  Me Sn  SnMe  3  H R  8  3  Me Sn  OR'  3  — 3  C0 R' 2  Me Sn  C0 R'  3  2  > — ( — H R  ?  Me Sn 3  g  OLI  R  ^  S  nMe  3  C0 R' 2  H  Scheme 16  substituted alkenes would have been accomplished. up  It may be noted that,  to the present time, methodologies leading to such alkenes have been  scarce. If  1 6  -  2 0  the  a,8-acetylenic  .  4 4  palladium(O)-catalyzed addition  of  hexamethylditin  to  esters proved to be a viable route for the preparation of  - 27 -  2,3-bis(trimethylstannyl)-2-alkenoates, be explored.  In  particular,  palladium(O)-catalyzed  we  were  then a further p o s s i b i l i t y could interested  in  effecting  addition of 'mixed' b i m e t a l l i c reagents  ing other Group IV elements such as s i l i c o n and germanium, for Me3SnSiMe3^ The  (utilizexample,  to a,^-unsaturated esters.  following  area of research.  the  chapters  discuss the progress made thus far i n this  - 28 -  RESULTS AND DISCUSSION  I.  P r e p a r a t i o n o f a,y9-acetylenic  The  requisite  methods.  alkynyllithium (equation turn,  a,8-acetylenic  In general,  4 2  esters  Some  (89) of  with  either  4 7  (equation  commercially a v a i l a b l e R  H+  methyl  14).  the  — —  u  methods.  LI +  R  (Scheme  available  diol  (91)  R—===—cc-jR  1 L  +  the  (81)  were  4 2  (14)  4  ICI  (15)  preparation  olefins. * " 4  17).  3  F o r example,  Thus,  treatment  a 10:1 m i x t u r e o f the  graphy o f the crude m i x t u r e o f these l a t t e r of  the  of  desired  1,1-dibromo  f o r the p r e p a r a t i o n o f methyl  w i t h hydrogen bromide (48%)  analysis),  the  of  some  product  the  monobromo  8-bromo-2-  commercially  product  4 9  (92)  Column chromato-  two m a t e r i a l s  (92).  olefin  i n refluxing benzene  c o r r e s p o n d i n g dibromo p r o d u c t , r e s p e c t i v e l y .  70%  (81)  e s t e r s were generated by the r e a c t i o n o f n - b u t y l -  (95)  afforded  CH  in  90  s e r v e d as an i n t e r m e d i a t e  the  1-alkynes  or were made v i a known  ciccyr  +  octynoate  and  corresponding  a l k y n y l l i t h i u m reagents r e q u i r e d f o r  (glc  chloroformate  89  l i t h i u m w i t h 1,1-dibromo  afforded  ethyl  known  r e a c t i o n of  1-alkynes  MeLI  w-halo-a,^-acetylenic  (94)  via  the  89 The  or  In general,  81 R  prepared  the r e q u i r e d a l k y n y l l i t h i u m s p e c i e s were,  g e n e r a t e d by d e p r o t o n a t i o n o f  with m e t h y l l i t h i u m  were  these m a t e r i a l s were p r e p a r e d by the  reagents  15).  esters  on s i l i c a  O x i d a t i o n o f the  gel  latter  - 29 -  Scheme 17  substance  with  pyridinium chlorochrornate  which was treated with Ph3P=CBr2 triphenylphosphine  and  Zn  treatment  with  a  solution  chloroformate afforded, In  a  17,  the  sequence  (prepared  dust ®) 4  corresponding tribromide (94).  afforded the aldehyde  3  to  from afford,  This l a t t e r of  carbon  in  tetrabromide,  96%  material,  n-butyllithium  i n 89% y i e l d , methyl  in  (93),  yield,  the  upon  successive  hexane  and methyl  8-bromo-2-octynoate  (95).  of steps e n t i r e l y analogous to those depicted i n Scheme  alcohol  6-chloro-l-hexanol  was  transformed  acetylenic ester methyl 8-chloro-2-octynoate (98)  into  the a,B-  i n an o v e r a l l y i e l d of  65%. Once a p a r t i c u l a r co-halo a,/J-acetylenic could be converted conveniently synthetically  manipulating  the  ester had been prepared,  it  into a s t r u c t u r a l l y related substance by halide moiety.  For example the  (99) was r e a d i l y prepared i n 93% y i e l d from the bromide (95) by  iodide utiliz-  We thank Professor L . Weiler for a generous sample of this compound.  - 30 -  Nal (CH ) CO  C0 Me 2  ing  the  Finkelstein  reaction the chloride 6-iodo-2-hexynoate (101)  could  utilizing  be phase  solution of (100)  3  reaction (100)  2  (equation  was  from  16).  converted  (102), i n 91% y i e l d .  prepared  the  By u t i l i z i n g the same  into  the  transfer catalysis.-'I  methyl  chloride  (100)  by  Thus, successive treatment of a  i n heptane with a mixture of sodium bromide, water and i n 72% y i e l d (equation  NaBr, H,0  ^ \ 1 o1  Adogen 464®  17).  C0 Me  (17)  2  s u b s t i t u t i o n reaction was also u t i l i z e d i n the preparation of the  bromide (104)  (equation 18).  prepared  treating  CH2CI2  iodide,  On the other hand, the bromide  corresponding  Adogen 464® afforded the bromide (101)  A  (16)  C0 Me  2  by  a  solution  with j> -toluenesulfonyl  4-dimethylaminopyridine.  TsO  The requisite j>-toluenesulfonate (1-03) was of ethyl 5-hydroxy-2-pentynoate  chloride i n the presence of  Subsequent  treatment  NaBr,DMF  of  a  pyridine  in and  solution of the  Br  (18) 104  C0 Et 2  We thank Mr. J . Wai for a generous sample of this compound.  - 31 E-toluenesulfonate  (103)  i n DMF with sodium bromide afforded (90%)  the  corresponding bromide (104). Another type functionalized  of  a,B-acetylenic  enyne.  Suzuki,-  ester in  )Z  that  was  required  of  an  internal  bond with B-bromo-9-borabicyclo[3.3.l]nonane afforded the corre-  sponding v i n y l bromide i n a haloboration  reactions  regio-  proceed  and  chemoselective  becoming  attached  intermediate envisaged  affords  felt  C-2  and C - l , respectively.  exclusively  utilizing  the ct,^-acetylenic We  to  the  Such  the  haloboration  the  boron  to  moiety  Protonolysis of the  2-bromo-l-alkene.  Hence  we  reaction for the preparation of  ester, methyl 8-bromonon-8-en-2-ynoate  (108)  (Scheme  that a suitable substrate for the haloboration reaction  was the diynoate  (106) ,  which  could  commercially available diyne (105).  be  obtained  readily  from  the  Thus, successive treatment of a THF C0 Me 2  1 .MeLl.THF 1 05  manner.  through c i s addition of the reagent  terminal acetylenic bonds only, with the bromine and  18).  a  a remarkable reaction, had shown  that treatment of a terminal acetylene i n the presence triple  was  2.CIC0 Me 2  Br  Scheme 18  C0 Me 2  - 32 -  solution equiv)  of  in  the  ether  approximately (107). very  l a t t e r material with a solution of methyllithium  a  and  methyl  1:1  mixture  T i c analysis different by  monoester  (106)  of  the  afforded  (glc  monoester (106)  therefore,  column  these  chromatography  was  two  on  substances  silica  i s o l a t e d i n 40% y i e l d .  s o l u t i o n of the l a t t e r material i n  esters were  gel.  were  readily  The  required  Subsequent treatment of a  with  CH2CI2  analysis),  and the diester  showed that the m o b i l i t i e s of the two  and,  separated  chloroformate  (1.3  B-bromo-9-borabicyclo-  [3.3.1]nonane afforded (87%) the bromide (108). Since  it  is  possible  to  effect  the  mono-hydrogenation J  1-alkyne function i n the presence of an i n t e r n a l t r i p l e that a diynoate such as (109) to an  enyne.  The  we  felt  could also serve as an e f f e c t i v e precursor  particular  6-hepten-2-ynoate (111)  bond,  of a  >  enyne  (equation 19).  that  was  required  The requisite  was  diynoate  methyl  (109)  was  ,C0 Me 2  ^/^S^  Pd-BaSQ ,H 4  ^  2  (19)  Hexane 109  111  r e a d i l y prepared (36% y i e l d ) by successive treatment of a of  THF  solution  commercially available 1,5-hexadiyne with a solution of methyllithium  i n ether  and  solution  of  methyl (109)  chloroformate.  Subsequent  hydrogenation  of  a  i n hexane i n the presence of 10% palladium-on-barium  sulfate afforded, after a  reaction  time  of  2  h,  the  corresponding  enyne(111) i n an i s o l a t e d y i e l d of 73%. It  should be noted that each of the a,B-acetylenic  esters  discussed  i n t h i s section exhibited spectral data i n f u l l accord with the assigned  - 33 structure (see Experimental Section). Some  of  the  a,/9-acetylenic  esters that were employed i n the work  described i n this thesis were prepared by known methods. acetylenic  esters  include  (116).  a,B-  ethyl 2-butynoate (70), methyl 2-pentynoate  (114), methyl 4-methyl-2-pentynoate siloxy-2-butynoate  These  42  (115) and ethyl 4-tert-butyldimethvl-  On the other hand, some of the a,B-acetylenic  esters were obtained from other researchers i n our laboratory, prepared them by u t i l i z i n g known methods.  These a,B-acetylenic  42  include methyl 3-cyclopropyl-2-propynoate  who  (117),  methyl  had  esters  7-tert-butyl-  dimethylsiloxy-2-heptynoate (118), methyl 6-tetrahydropyranyloxy-2-hexynoate (119), methyl 5-(2-cyclopentenyl)-2-pentynoate cyclohexenyl)-2-butynoate  (121), ethyl 5-chloro-2-pentynoate  methyl 7-bromo-2-heptynoate  II.  (120), methyl 4-(3(122)-* and 4  (123).  Synthesis of a l k y l (Z)- and (E)-2,3-bis(trimethylstannyl)-2alkenoates and (E)-N,N-dimethyl-2,3-bis(trimethylstannyl)-2alkenamides  A.  Preparation of a l k v l (Z)- and (E)-2.3-bis(trimethylstannyl)-2alkenoates  In the general introduction of this thesis i t was mentioned that our i n i t i a l objective was to explore the p o s s i b i l i t y of preparing a l k y l  2,3-  bis(trimethylstannyl)-2-alkenoates  that  employed  previously  in  our  via  a  route  laboratory  different  utilizing  from  organocopper(I)  - 34 reagents.21  In doing so we hoped to  overcome  problems associated with using organocopper(I) were mentioned i n the general introduction. the  preparation  some  of  the  reagents. Mitchell^  practical  These problems had  3 a  reported  (2)-1,2-bis(trimethylstannyl)-1-alkenes  of  by  palladium(O)-catalyzed addition of hexamethylditin to 1-alkynes. we  sought  to  the Thus,  investigate the p o s s i b i l i t y of adding hexamethylditin to  a,8-acetylenic esters, u t i l i z i n g palladium(O) c a t a l y s i s . In the f i r s t such e f f o r t directed towards probing the p o s s i b i l i t y of adding hexamethylditin to an a,B-acetylenic catalysis,  the following reaction was attempted.  2-butynoate  (70)  in  at  room  To a solution of ethyl  THF was added 1 equivalent of hexamethylditin and  0.01 equivalents of (PPl^^Pd. stirred  ester u t i l i z i n g palladium(O)  After  the  reaction  mixture  had  temperature for 21 h glc analysis of an aliquot i n d i -  cated the absence of a peak corresponding to ethyl 2-butynoate the  appearance  of  another  major  development with 95:5 petroleum indicated  the  presence  component (Rf - 0.90) solvent, oil  followed  peak.  Tic  ether-diethyl  analysis  ether)  of  corresponding to hexamethylditin.  by  afforded  subsequently butenoate  and  (silica  gel,  the  mixture  and a minor  Removal of  the  column chromatography of the residual orange-red  82%  identified  (124)  (70)  of one major component (Rf - 0.11)  on s i l i c a gel and d i s t i l l a t i o n ( 7 0 - 7 5 ° C / 0 . 1 Torr) of  obtained,  been  of  a c l e a r , colorless o i l .  as  ethyl  the  oil  thus  This material was  (Z)-2,3-bis(trimethylstannyl)-2-  from an analysis of i t s spectral data ( i r , ms, ^H nmr).  Structural e l u c i d a t i o n of (124) was also f a c i l i t a t e d  by  chromatographic  behaviour  sample of ethyl  (E)-2,3-bis(trimethylstannyl)-2-butenoate  comparing  its  and spectral data with those of an authentic (77).  This  - 35 -  Me Sn  SnMe  3  H  Me  Me Sn  3  C0 Et  3  2  H  C0 Et  Me  2  124  SnMe  3  77  l a t t e r material had been prepared by the addition  of  trimethylstannyl-  copper(I)•dimethyl sulfide complex to ethyl 2-butynoate Chromatographically,  the  showed d i f f e r e n t behaviour.  two For  geometric example,  (70).  Isomers  tic  2 1  (124)  analysis  and (77),  (silica  gel,  development with 95:5 petroleum ether-diethyl ether) showed that the (Z) isomer (124) 0.32). (77)  (Rf - 0.11)  Furthermore,  was more polar than the (E) isomer (77)  glc  analysis  one  distinct  component  was  obtained.  unstable  since  a  clean  On  analysis of a pure sample of the (Z) i s omer (124) thermally  =  of a pure sample of the (E) isomer  indicated that i t was thermally stable since a  with  (Rf  chromatogram  the other hand, glc  indicated that i t  was  chromatogram with one major component and  several u n i d e n t i f i e d components was obtained. The  nmr and i r spectra of  interpreted  and  they  the  of  the  (Z)  isomer  (124)  showed some d i s t i n c t differences  sponding spectra of the (E) isomer spectrum  (Z)  isomer  (77).  (124)  For  moiety,  and  an  absorption  readily  from the corre-  example,  the  infrared  showed an absorption at 1700 cm" , 1  a t t r i b u t a b l e to the carbonyl stretching frequency of the ester  were  at  775  rocking frequency of a trimethylstannyl  a,^-unsaturated  cm* due to the tin-methyl 1  group.  In  contrast,  the  ir  spectrum of the (E) isomer exhibited a carbonyl absorption at 1685 cm" . 1  The ^-H nmr spectrum of the (Z)  isomer  9-proton  ( J_s -H  singlets  at  S  0.22  2  n  (124) =  5  2  ,  consisted 5  H z  ^  a  n  d  6  of 0  ,  2  5  two  sharp  < -Sn-H 2j  =  - 36 53.5  Hz),  a  3-proton t r i p l e t at S 1.27  at 6 2.07  (^J.Sn-H - 10 Hz, ^Isn-H ~ ^  4.15  «= 7 Hz).  (J  (77) ( J J g  n  S n  .  -  H  _ L j  -  54 49  resolution (Z)  Hz), Hz).  mass  a n c  *  2-proton quartet  a  at  5  In comparison, the ^H nmr spectrum of the (E) isomer  exhibited 9-proton singlets at 6 0.14  2  3  **z)  (J - 7 Hz), a 3-proton s i n g l e t  and In  ( J.Sn-H " 2  5  3  H z  a 3-proton s i n g l e t at S 2.22  addition  to  the  above  )  a  n  d  S  0  ( J.s -H " 4  1  ,  1  n  spectral  data,  2  5  Hz  >  high  spectrometry showed that the molecular formula for the  isomer (124) was C 2 2 6 ° 2 2 H  S n  1  As a consequence of addition  of  the  hexamethylditin  investigate the generality of a,/9-acetylenic  esters.  efficient, to  facile  palladium(O)-catalyzed  ethyl 2-butynoate  this  reaction  (70),  utilizing  we decided to a  variety  As such, the compounds of general structure  l i s t e d i n Table I were prepared i n isolated y i e l d s ranging from 95%.  of (83)  64%  to  It i s pertinent to note that many of the y i e l d s l i s t e d i n Table I  have not been optimized. formed  at  room  Although the  temperature  reactions  (entries 2-6),  were  In  each  case  per-  i t was found that reaction  times were decreased when the reactions were c a r r i e d THF.  initially  out  in  refluxing  (Table I) the progress of the reaction was e a s i l y  monitored by t i c and/or glc analyses. present i n the a,6-acetylenic  A variety  of  functional  groups  esters are tolerated: carbon-carbon double  bonds (entries 8-10), ether functions  (entries  (entry 11) and primary halides (entries 12-19).  5-7),  a  vinyl  bromide  In each case (Table I ) ,  the ^H nmr, i r and mass spectra of the reaction product were i n complete agreement with the assigned structure. In  a l l cases studied (Table I ) ,  13, the reactions were clean and the  apart from that summarized i n entry products  were  readily  isolated.  - 37 -  Table I :  C o n v e r s i o n o f a , / 3 - a c e t y l e n i c e s t e r s (90) i n t o a l k y l (Z)-2,3-bis (trimethylstannyl)-2-alkenoates (83)  Me Sn  SnMe  3  C0 R'  Me Sn ,THF Pd(PPh ).  2  6  2  /  3  3  Entry  \ = / \  R  4  90  C0 R' 2  83  90  R  R'  Conditions  Time (h)  83  A A A A A A B B B B B B B B B B B B B  4 18 36 28 62 15 4 6 3 4 2 6 8 5 6 6 5 15 6  124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142  3  1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19  70 114 115 117 118 119 116 120 121 111 108 122S 104 100 101 102 123 95 99 c  d  c  c  c  c  Me Et i-Pr cyclopropyl tert-BmMe SiO(CH )4 THPOCH CH CH tert-BuMeoSiOCHo 2-(2-cyclopentenyl)ethyl (3-eyelohexenyl)methyl CH =CHCH CH CH -C(Br)CH (CH ) C1CH CH BrCH CH C1CH CH CH BrCH CH CH ICH CH CH BrCH (CH )3 BrCH (CH ) ICH (CH ) 2  2  2  2  2  2  2  2  2  2  2  2  2  2  2  2  2  2  2  2  2  2  2  2  2  2  2  2  2  Reaction conditions:  4  4  2  3  3  Et Me Me Me Me Me Et Me Me Me Me Et Et Me Me Me Me Me Me  e  f  Yield (%)  95 88 90 83 82 83 83 73 74 85 64 89 66 86 84 79 78 83 76  A:  performed at room temperature ( 2 0 ° C ) i n THF u t i l i z i n g approx. 0.01 e q u i v o f P d ( P P h 3 ) and 1 equiv of MegSn . B: performed i n r e f l u x i n g THF u t i l i z i n g reagents as i n A . Y i e l d of i s o l a t e d , p u r i f i e d product. These m a t e r i a l s were p r e p a r e d by D r . J . M . C h o n g . T h i s m a t e r i a l was p r e p a r e d by D r . B . A . Keay a c c o r d i n g to the procedure of C h o n g . T h i s r e a c t i o n was performed a t 5 5 - 6 0 ° C . T h i s r e a c t i o n was performed u t i l i z i n g a d i f f e r e n t s our c e o f p a l l a d i u m ^ ) - ' - ' (see t e x t ) . T h i s m a t e r i a l was p r e p a r e d by Mr. J . W a i . ^ 4  2  b c d  4 2  4 2  e f g  b  4  - 38 Tic  analysis  of  the crude product derived from substrate  13), however, showed the presence of one unidentified  components.  Similarly,  major  (104)  component  and  hexamethylditin  and ethyl 6-bromo-2-pentynoate  glc and t i c analyses indicated that, as the unidentified  components  jected to workup. graphed  three  were  produced,  reaction  on  silica  components, (104).  progressed,  Since more  the reaction mixture was sub-  After the red-black o i l thus obtained  times  several  glc analysis of an aliquot i n d i -  cated the presence of one major component and several other including  (entry  was  chromato-  g e l , a c l e a r , colorless o i l (compound  (136)) was i s o l a t e d i n a y i e l d of 66%. The experiment summarized additional tions,  comment.  the product (134)  hexamethylditin (108)  It  in  was  entry  11,  Table  also  deserves  envisaged that under the reaction condi-  a r i s i n g from the  Pd(O)-catalyzed  to the r e q u i s i t e ester, methyl  could undergo further  I,  reaction  (equation  addition  of  8-bromonon-8-en-2-ynoate 20).  In  particular,  (20) based on S t i l l e ' s w o r k , ® we envisaged the p o s s i b i l i t y of an intramolec2  u l a r Pd(0) cross-coupling reaction between the v i n y l bromide and stannane 20).  moieties  of  However, when  hexamethylditin  and  a  (134)  to afford the c y c l i c diene (143)  solution  of  (108)  in  THF was  vinyl-  (equation  treated  with  (PPt^^Pd, and the mixture was s t i r r e d for 20 h at  room temperature, glc analysis indicated that no reaction had  occurred.  - 39 Moreover,  upon refluxing the mixture for 50 h, a considerable amount of  unidentified However,  material  after  was  column  evident  by  both  and  glc  addition  product  (134)  isolated. As  a consequence of the f a i l u r e of the above reaction to proceed i n  THF, the effect of changing the solvent was investigated. a  analyses.  chromatography of the crude o i l , a minor amount  (<10%) of a mixture of the diene (143) and the was  tic  solution  As such, when  of (108) i n either CH3CN, DME or PhH was treated with hexa-  methylditin and (PPl^^Pd and the mixture was s t i r r e d for up to 50 h 60°C,  several  analyses). out  in  unidentified  materials  were  evident  (glc  Similar results were obtained when the reaction was the  absence  of  solvent (neat).  tic  carried  Therefore, i t was decided to  investigate the reaction u t i l i z i n g an alternative source of particular,  and  at  Pd(0).  In  we were attracted to a recent r e p o r t , ^ which described how  a mixture of palladium(II) acetate, triphenylphosphine and triethylamine was  used  to generate a source of Pd(0)  in situ .  Thus, a solution of  the ester (108) i n THF was treated with hexamethylditin and an solution  of Pd(0) i n THF.  After the mixture had been s t i r r e d at reflux  for 2 h, t i c and glc analyses of an aliquot (108)  and  the  presence  of  64%  indicated  a new component.  followed by column chromatography afforded  of  the  of  the  absence  of  Removal of the solvent,  crude  oil  on  silica  gel,  of a compound which was subsequently i d e n t i f i e d as methyl  (2)-2,3-bis(trimethylstannyl)-9-bromo-2,9-nonadienoate spectra  in situ  the  The  (134).  l a t t e r compound were f u l l y i n accord with the  assigned  structure. The diene (143) was not detected i n the  crude  product  mixture  by  - 40 either glc or t i c analyses. did  not  lead  to  the  Furthermore, prolonging the  (134).  The  difference  in  reactivity  d i f f e r e n t sources of Pd(0) remains unclear. intramolecular  time  formation of (143), but resulted instead i n the  formation of unidentified materials and a lower y i e l d product  reaction  Pd(0)-catalyzed  coupling  of  addition  observed by using two  Attempts of  the  the  at vinyl  effecting  an  bromide  and  vinylstannane moieties i n (134) w i l l be discussed i n a l a t e r section t h i s thesis (Section VI of the Although  the  discussion).  Pd(0)-catalyzed  addition of other hexaalkylditins to  a,B-acetylenic  esters was not thoroughly investigated,  the  of  addition  f a c i l e process. in  commercially  available  i t was found that  hexa-n-butylditin  was not a  For example, when a solution of ethyl 2-butynoate  (70)  THF was treated with hexa-n-butylditin and Pd(PPh.3)4 and the mixture  was s t i r r e d at room temperature or at a (approximately 21).  of  45°C)  slightly  elevated  temperature  the reaction f a i l e d to go to completion (equation  In both reactions,  glc  or  tic  analyses  of  the  BujSn Pd(PPh ) ,THF  Me—==i—C0 Et  a  2  4  mixture  SnBut  \  /  /  \  .rvBUaSn.  Me  70  crude  f  2  1  )  cOjEt 144  indicated  the  presence  of  the ester (70) and h e x a - n - b u t y l d i t i n .  best y i e l d of the addition product (144) chromatography  on  silica  gel  was 31%.  that was obtained after Mitchell  4 3 b  useful.  column  had also reported  that the Pd(0)-catalyzed addition of hexa-n-butylditin to not s y n t h e t i c a l l y  The  1-alkynes  is  - 41 Of the a,B-acetylenic esters pentynoate  (145)  42  failed  reaction (equation 22). hexamethylditin  to  undergo  the  only the  ethyl  Pd(0)-catalyzed  Pd(PPti3)4  Furthermore, glc analysis of an  crude mixture showed only the presence of (145)  reaction  addition and  i n THF was refluxed for 4 days, no product was detected  d i t i n , thus i n d i c a t i n g that no reaction had occurred. this  4,4-dimethyl-2-  Thus, when a solution of (145),  by either glc or t i c analyses. of  studied,  (equation  aliquot  and hexamethylThe  failure  of  22) to proceed most l i k e l y indicates that the  Me Sn ,THF 6  ==—C0 Et  —  2  P d  2  (PPh ) 3  '  4  no reaction  (22)  145  t r a n s i t i o n state of the Pd(0)-catalyzed addition of an  ester  a,y9-acetylenic  about the t r i p l e bond. Pd(0)-catalyzed Mitchell,  4 3 0  such as (145)  The f a i l u r e of the ester (145)  addition  who reported  reaction that  possible  is  in  accord  in  to  with  3,3-dimethyl-1-butyne  undergo the  also  Scheme  19.  The  first  step  by  the  cis-PdLo(SnMe3)o  l a t t e r species to the t r i p l e bond afford  an  of  failed  to  catalytic  complex of  [A].-*  the  6  afford  a  Coordination of this  a,^-acetylenic  intermediate represented by [B].  i n s e r t into one of the tin-palladium bonds  cycle  can be envisaged to be the 2  planar  work  conditions.  oxidative addition of hexamethylditin to the PdL, c a t a l y s t to square  the  pathway for the Pd(0)-catalyzed addition of hexamethyl-  d i t i n to a ,/3-acetylenic esters i s represented depicted  to  i s sensitive to s t e r i c crowding  react with hexamethylditin under Pd(0)-catalysis A  hexamethylditin  ester  would  The t r i p l e bond could then to  afford  an  intermediate  - 42 -  Scheme 19  depicted  by  [C].  This l a t t e r species could undergo reductive elimina-  t i o n to afford the corresponding addition product (83) and the palladium catalyst  PdL£.  The palladium catalyst PdL2 would then undergo another  catalytic cycle.  The c a t a l y t i c cycle depicted i n Scheme 19 accounts for  the observed stereochemical configuration of the addition products A s i m i l a r pathway has been evoked configuration d i s i l a n e s to  of  to  account  for  the  (83).  stereochemical  products a r i s i n g from the Pd(0)-catalyzed addition of  1-alkynes.^7  In the e a r l y part of t h i s section of the discussion i t was mentioned that  glc  chromatograms  of  alkyl  (Z)-2,3-bis(trimethylstannyl)-2-  - 43 alkenoates  showed evidence of decomposition.  speculations  in  which  a  pure  stannyl)-6-chloro-2-hexenoate (90-95°C/0.01 T i c analysis ether)  observation  led  that these compounds might be thermally unstable.  the thermal i n s t a b i l i t y of these compounds experiment  This  sample (137)  was  of methyl  verified  in  to  Indeed, an  early  (Z)-2,3-bis(trimethyl-  (entry 14, Table  I)  was  distilled  Torr) i n a Kugelrohr bulb-to-bulb d i s t i l l a t i o n apparatus. ( s i l i c a g e l , development with 95:5 petroleum  indicated  ether-diethyl  the presence of two major components.  component (Rf •= 0.21)  The more polar  corresponded to the (Z) isomer (137), whereas  less polar component (Rf «=• 0.42)  was subsequently found to correspond to  methyl (E)-2,3-bis(trimethylstannyl)-6-chloro-2-hexenoate chromatography  the  (146).  Column  of the crude mixture on s i l i c a gel afforded two separate  oils,  corresponding to (137)  and (146).  oils  to reduced pressure (vacuum pump, 0.05 Torr) for approximately 1 h  afforded 60% of the (Z) isomer (137) The  Subjection  and 30% of the  large proportion of the (E) isomer (146)  of  each  (E)  of  isomer  a  facile  process.  Consequently, a l l of the a l k y l  methylstannyl)-2-alkenoates were  (146).  that was formed during the  d i s t i l l a t i o n indicated that the thermal isomerization of the (Z) is  these  isomer  (Z)-2,3-bis(tri-  that were prepared, as summarized i n Table L,  not d i s t i l l e d but were subjected to reduced pressure (vacuum pump,  0.05-0.1 Torr) to remove any traces of solvent for a period of 1-2 h. The spectral data derived from the interpreted  and,  straightforward. at  1685  cm"  a,8-unsaturated  1  as  a  consequence,  (E)  isomer  (146)  the  structural  For example, the i r spectrum exhibited attributable  was  readily  assignment an  was  absorption  to the carbonyl stretching frequency of an  ester function and an absorption at 775 cm" due to 1  the  - 44 tin-methyl  rocking  spectrum of (146) ( J 2  S n  .  H  frequency  of a trimethylstannyl group.  consisted of two sharp 9-proton  - 54 Hz) and 6 0.26  ( J.Sn-H ~ 2  1.73-1.82, a 2-proton multiplet at 6 2-proton  t r i p l e t at S 3.55  Furthermore,  high  5  5  Hz  )>  singlets  The . H nmr at  6  0.17  2-proton multiplet at 6  a  2.60-2.66  ( lsn-H 3  ~  6  0  Hz  >•  a  (J » 7 Hz) and a 3-proton s i n g l e t at 6 3.71.  resolution  mass  spectrometry  verified  that  the  molecular formula was C^3H2702ClSn2. Up  to  t h i s point i n the discussion conclusive evidence for assign-  ment of stereochemical configuration of the compounds obtained from Pd(0)-catalyzed  addition  has not been presented. (146),  which  had  of  hexamethylditin to a,/3-unsaturated esters  Since we had  presumably  managed  of both compounds could be elucidated.  nOe  difference  s i n g l e t at 6 3.70  only  a  compound  relative  stereochemistry configuration  and (137) was unequivocally established by performing  experiments on each compound. (-OMe) i n compound (137)  enhancement (-SnMe.3).  Thus, i r r a d i a t i o n of the  caused signal enhancement  one of the 9-proton singlets (6 0.25,  and 6 0.26  isolate  The stereochemical  i r r a d i a t i o n of the singlet at 6 3.71 (-OMe) signal  to  arisen from the thermal isomerization of  (137), an opportunity had arisen i n which the  of compounds (146)  the  -SnMe.3). in  of  On the other hand,  compound  (146)  caused  of both of the 9-proton singlets at S 0.17 (-SnMe.3) The results of the nOe difference experiments  are  - 45 consistent  only  with  structures (137)  the  stereochemical  and (146), i . e .  configurations  depicted i n  (Z) and (E) respectively.  It should be  noted that the r e s u l t of the nOe difference experiment on compound (137) showed that, of the two 9-proton s i n g l e t s ,  the one appearing  at  higher  f i e l d corresponds to the a-Me3Sn group. To  ensure  that  the thermal rearrangement of the (Z) isomer was an  e f f i c i e n t process the following experiment was performed. of  methyl  (Z)-2,3-bis(trimethylstannyl)-6-chloro-2-hexenoate  heated, with s t i r r i n g , at approximately 75°C. tic  (137) was  After a period of  24  h,  analysis indicated the appearance of a new material and the absence  of the s t a r t i n g material (137). afford  a  colorless  oil,  i d e n t i c a l with methyl (146). As isomer  The pale yellow o i l  a  consequence of the e f f i c i e n t  (137)  in  into  the  process  Table  (E)  isomer  thermal isomerization of the (Z) (146),  II  the  generality  of  the  was investigated by employing a v a r i e t y of a l k y l (83).  As such, the compounds  were prepared i n y i e l d s ranging from 66-98%. tolerate  a  variety  of  The  functional  The functional groups that were tolerated included a l k y l groups  (entries 1-4), 5-7),  to  (E)-2,3-bis(trimethylstannyl)-6-chloro-2-hexenoate  isomerization process was found to groups.  distilled  which was s p e c t r a l l y and chromatographically  (Z)-2,3-bis(trimethylstannyl)-2-alkenoates listed  was  This l a t t e r material was isolated i n a y i e l d of 96%.  isomerization  silyl  and  tetrahydropyranyl ether  functions  (entries  carbon-carbon double bonds (entries 8-10), a v i n y l bromide (entry  11) and primary halides (entries 12-14). II  A neat sample  exhibited  The compounds l i s t e d i n  Table  nmr, i r and mass spectra that are i n complete agreement  with the assigned structures  (78).  - 46 Table I I :  Conversion of a l k y l (Z)-2,3-bis(trimethylstannyl)-2alkenoates (83) into a l k y l (E)-2,3-bis(trimethylstannyl)2-alkenoates (78)  Me Sn  SnMe,  3  Me Sn  H R  Entry  —  H  C0 R'  R  2  83  83  CO,R'  3  R  R'  78  SnMe  3  Reaction conditions (°C/h)  3  78  Yield (%) b  1  124  Me  Et  79/30  77  82  2  125  Et  Me  85/18  147  82  3  126  i-Pr  Me  80/6  148  98  4  127  cyclopropyl  Me  85/7  149  83  5  128  tert-BuMeoSiOCCHoV|  Me  95/12  150  94  6  129  THPOCH CH CH  Me  80/6  151  93  7  130  tert-BuMeoSiOCHo  Et  81/12  152  86  8  131  2-(2-cyclopentenyl)ethyl  Me  80/8  153  81  9  132  (3 -cyclohexenyl)methyl  Me  88/48  154  88  10  133  CH =CHCH CH  Me  80/14  155  81  11  134  CH -C(Br)CH (CH )  Me  83/36  156  66  12  137  C1CH CH CH  2  Me  75/24  146  96  13  95  BrCH (CH )  3  Me  85/40  157  80  14  99  BrCH (CH )4  Me  86/21  158  88  2  2  2  2  2  2  2  2  2  2  2  2  2  2  3  2  A l l reactions were performed neat at a temperature of 7 5 - 9 5 ° C . Y i e l d of i s o l a t e d , d i s t i l l e d product.  - 47 In general, i t was found facile  that  the  isomerization  reaction  process that occurred r e a d i l y at moderate temperatures  over periods of 6-48 However,  the  hours  isomerization  not a clean reaction. presence  of  unidentified  (Table  II)  in  the  of compound (134)  T i c analysis  of  the  absence  was  (75-95°C)  of  solvent.  (entry 11, Table II) was  crude  oil  indicated  components.  Furthermore,  the  yellow  the crude o i l had been s t i r r e d at 83 C for 36 h the  reaction  product  C  in  a  yield  of  66%.  mixture  isomerization  process  (83)  thermal  could perhaps  sample  of  results  i n p a r t i a l isomerization.  time,  some  be  overcome  if  toluene.  i n s t a b i l i t y of some of the (Z) isomers  l i s t e d i n Table II (entries 1-4, these  analysis  was not investigated the problem associated  the reaction was performed i n a solvent such as the  was  Although the effect of solvent on  with the isomerization of compound (156)  Interestingly,  After  (156)  At shorter reaction times t i c  indicated only p a r t i a l isomerization. the  the  the desired compound (136), but also present were numerous  contained some insoluble s o l i d material which was not i d e n t i f i e d .  isolated  a  7) i s such, that storage of a neat  compounds at 5°C for a period of up to several months  decomposition  of  However, over such a long  period  the compounds (83) also occurs.  p a r t i c u l a r l y evident from the physical appearance  of  the  of  This i s  crude  oils,  which, upon storage for extended periods of time, become pale yellow and contain  insoluble  process  is  a  high temperature  solid  facile  material.  (83)  the  isomerization  one i f the reaction is performed at a moderately  (75-95°C).  A possible mechanistic pathway compounds  Nevertheless,  to  compounds  (78)  for is  the  thermal  isomerization  depicted by equation 23.  of Upon  -  Me Sn  4 8  -  OSnMe  SnMe Me Sn  3  3  H  3  C0 R'  R  C0 R'  Me Sn  2  3  (23)  R  2  3  OR'  159  83  SnMe / O  Me Sn 3  R  SnMe  3  78  # 3  R OR" 160  examination apparent, cis  of  that  m o l e c u l a r models c o r r e s p o n d i n g to compounds t h e r e e x i s t s a severe s t e r i c  trimethylstannyl  corresponding to relieved Hence i t  since  groups.  compounds the  intermediate  to  the  of  allenoate  the  oxygen  four-centered transition (159).  this  steric  species a  the  transition atom  state,  interaction  has  been  conditions,  Presumably, t h i s  state  depicted  (78) latter  by  (160).  w i t h the t i n atom c o u l d r e s u l t  which  would  lead  to  the  in a  allenoate  the  thermodynamically  more  (78). the  isomerization  pathway d e p i c t e d i n Scheme 20.  In  the  p r e v i o u s pathway i t was mentioned t h a t , (78)  two  T h i s l a t t e r s p e c i e s c o u l d then undergo i s o m e r i z a t i o n v i a  Alternatively,  isomers  is  i n m o l e c u l a r models  reaction  (159).  a f o u r - c e n t e r e d t r a n s i t i o n s t a t e to a f f o r d stable product  i n t e r a c t i o n between the  the o t h e r hand,  t h a t under  could arise v i a  Coordination  species  (78) ,  it  two t r i m e t h y l s t a n n y l groups are now t r a n s - r e l a t e d .  c o u l d be e x p e c t e d ,  rearranges  On  (83),  would be expected  process  could  discussion  proceed dealing  based on s t e r i c  via with  factors,  the  to be thermodynamically more s t a b l e  the the (E) than  - 49 -  Me Sn  SnMe  3  Me Sn  3  3  +  Me Sn* 3  C0 R' 2  83  161  Me Sn  C0 R'  3  2  +  R  SnMe  Me Sn* 3  R  3  78  162  Scheme 20  the (Z) isomers (83). under  the  As such, i t could be  reaction  conditions,  the  (Z)  expected isomers  that,  initially,  (83) could undergo  homolytic cleavage of the carbon-tin bond alpha to the ester function to afford  the  vinyl  radical  (161)  and a trimethylstannyl r a d i c a l .  inversion of configuration at a v i n y l r a d i c a l centre has been be  a  (161) in  facile  process.^  8  literature,^  to  Hence, we can consider that the v i n y l r a d i c a l  i s i n equilibrium with the v i n y l r a d i c a l (162).  the  shown  The  which  suggests  that  a  Based on evidence  favourable  electronic  i n t e r a c t i o n exists between the t i n atom and the ester function when they are  cis  related,  r a d i c a l (162).  we  can  expect  the equilibrium to favour the v i n y l  This l a t t e r species could react with compound (83) or i t  could react with a trimethylstannyl r a d i c a l to afford, i n each case, thermodynamically more stable product  (78).  In connection with the discussion of the isomerization of (83)  to  compounds  (78),  it  is  the  pertinent  to  compounds  note that M i t c h e l l ^  reported the photochemical isomerization of the ester (163)  4 3  to the ester  - 50 (164)  (equation 24). Me Sn  SnMe  3  Me Sn  3  H  -  H  C0 Me  3  2  —  C0 Me  H  2  SnMe  163 Returning  to  the  (24)  H 3  164  Pd(0)-catalyzed  addition  of hexamethylditin to  a,B-acetylenic esters, when the reaction was c a r r i e d out on the diynoate (112)  the s t r u c t u r a l l y interesting diene (165) was i s o l a t e d i n 56% y i e l d  (equation 25).  For example, when a solution of the ester (112)  i n THF  ,C0 Et 2  _  ^  Me Sn ,THF Pd(PPh ) 6  Et0 C 2  2  3  y  (  ^  (25)  S n M e j  4  112  was  treated  with  (PPl^^Pd  and  hexamethylditin  and the mixture was  refluxed for 9 h, glc analysis of an aliquot indicated the one  major  (165).  component,  which  was  by  analysis  of  of  subsequently i d e n t i f i e d as the diene  The s t r u c t u r a l assignment of the  established  presence  the  latter  compound  spectral data.  was  clearly  For instance,  the i r  spectrum showed, an absorption at 1698 cm" attributable to the carbonyl 1  stretching cm"  1  of  frequency of an a,y9-unsaturated  a t t r i b u t a b l e to the carbon-carbon double bond stretching an  frequency  a,^-unsaturated ester and an absorption at 771 cm" attributable 1  to the tin-methyl rocking frequency. one 6-proton s i n g l e t at 6 0.51 1.28  ester, an absorption at 1611  The H nmr of (165)  ( J_s -H 2  n  1  =  consisted  of  ^0 Hz), a 6-proton t r i p l e t at 6  (J = 7 Hz), a 2-proton quintet at 6 2.02  (J =  8  Hz),  a  4-proton  - 51 t r i p l e t at 6 2.87 Hz).  In  (J - 8 Hz) and a 4-proton quartet at 6  addition  to  the  above  4.17  (J  -  7  spectral data, high resolution mass  spectrometry showed that the molecular formula for (165) was Ci5H2204 Sn  It  is  pertinent to note that the formation of compound (165) cannot be  wholly accounted for by the c a t a l y t i c pathway depicted i n Scheme 19. alternative  pathway  which  could  account  An  the formation of (165)  for  remains unclear. It i s thus apparent from the preceeding discussion i n that  the  palladium(O)-catalyzed  addition  of  this  section  hexamethylditin  a,B-acetylenic esters proceeds smoothly and e f f i c i e n t l y to afford (83).  (Z)-2,3-bis(trimethylstannyl)-2-alkenoates  l a t t e r compounds are thermally unstable and, upon  Furthermore, warming  to  to  alkyl these  75-95°C,  rearrange cleanly to the corresponding (E) isomers ( 7 8 ) .  B.  Spectral data of a l k v l (Z)-  and (E)-2.3-bis(trimethylstannyl)-2-  alkenoates  During  the  course  of  the preceeding discussion, i t was mentioned  several times that the spectral data of a pair of geometrically isomeric alkyl  2,3-bis(trimethylstannyl)-2-alkenoates  ences , and as such the assigned  stereochemical  spectral  data  configuration.  can  show some d i s t i n c t d i f f e r provide  Such  evidence  differences  isomers,  (78)  the  are c l e a r l y  seen i n the selected ^H nmr chemical s h i f t data of a series of (Z)  for  (E)  and  and (83) respectively (Table III) and i n the ^-H nmr  spectra depicted i n Figures 1 and 2 (entry 9, Table I I I ) .  A  character-  - 52 -  i s t i c trend that can be noticed i n Table III i s that the chemical s h i f t s of  the two 9-proton singlets (Me3Sn groups) of the (Z) isomers (83)  very close together shifts  of  the  (within 0.03 ppm).  On the other hand, the  7  the  protons  of  Moreover, the  Table  entry 3.  Thus, i n the  A l l of the examples  nmr spectra of methyl  the 7-proton of the (E) isomer resonates of  the  (Z)  isomer  (entry  3).  (Z) -  (126) at  and  and (148)  lower  field  Regardless  given  III)  7  the  than those of the  (E)-2,3-bisrespectively, than  the  7  of the anomalous  behaviour of these l a t t e r compounds, the fact that i n (Table  shifts  III follow this trend except for the p a i r of isomers given i n  (trimethylstannyl)-4-methyl-2-pentenoate,  proton  chemical  the l a t t e r compounds are further downfield than  those of the corresponding (2) isomers (83). in  chemical  two 9-proton singlets (Me3Sn groups) of the (E) isomers  (78) are further apart (up to 0.1 ppm). of  are  all  other  cases  protons of the (Z) isomer resonate at higher f i e l d  (E)  isomer  anisotropic  is  of  particularly  when  one  considers  the  function.  On the basis of this effect one would expect the 7-protons of  the (Z) isomers ( i . e .  effect  unexpected,  the carbonyl group of the ester  those compounds i n which the ester function i s  to the 7-protons) to resonate at lower f i e l d . case,  presumably  the  ester  Since  this  is  not  cis the  function i s oriented i n a conformation i n  which the s h i e l d i n g and/or deshielding effects of the carbonyl group are minimal.  This  presumption  i s based on the fact that i n the series of  t r i s u b s t i t u t e d vinylstannanes of general structure (80A) In  which  E —  an  (vide  infra).  a l k y l group, the chemical s h i f t of the v i n y l methyl  group i s approximately 2.1 ppm.  This value i s i n close  the  the corresponding v i n y l methyl group (6  chemical  shift  value  of  agreement  with  - 53 Table I I I :  Selected --H nmr chemical s h i f t data for compounds (83) and (78)  B  A  Me Sn  SnMe  3  B  Me Sn  3  H R  C0 R'  3  2  H C0 R'  R  2  83  SnMe 78  3  A  Chemical S h i f t (Sn Me ) (Sn Me ) 5(7-pro6 6 ton) 3  Entry  R  R'  1  Me  Et  2  Et  Me  3  i-Pr  Me  4  cyclopropyl  Me  5  tert-BuMeoSiOCHo(CHo)  6  tert-BuMe SiOCH  7  (3 -cyclohexeny1)me thy1  Me  8  CH =CHCH CH  Me  9  C1CH CH CH  10  11  2  2  2  2  3  2  Me Et  2  Me  BrCH (CH )  3  Me  BrCH (CH )  4  Me  2  2  2  2  2  2  Configu- Comr a t i o n pound Z E Z E Z E Z E Z E Z E Z E Z E Z E Z E Z E  124 77 125 147 126 148 127 149 128 150 130 152 132 154 133 155 137 146 140 157 141 158  A  B  3  3  b  0.,22 0..25 0..21 0..26 0..25 0,.23 0..23 0,.26 0..24 0.,25 0..20 0.,24 0,.18 0.,20 0,.24 0..26 0..25 0.,26 0..25 0..26 0..24 0..25  0..25 0,.14 0..22 0,.18 0,.28 0,.20 0..23 0,.17 0..25 0..15 0..23 0.,15 0..20 0.,10 0..245 0.,16 0..26 0.,17 0..25 0.,17 0..25 0.,15  2,.07 2 .22 2,.35 2 .49 2 .77 2 .66 1..73 1..78 2,.35 2,.44-2 .51 4..35 4..34 2..21-2,.38 2.,36-2..53 2..38-2,.45 2.,53-2,.61 2..47 2.,60-2..66 2..36 2.,47-2..54 2..34 2..48  Chemical s h i f t (6) was measured r e l a t i v e to the chloroform signal fin (6 7 . 2 5 ) i n ppm. The spectra were recorded i n deuteriochloroform solutions. DU  S (7-protons) refers to the chemical s h i f t of the protons 7 to the ester function.  - 54 -  Me Sn  C0 Me  3  2  SnMe,  X F i g . 2:  The 400 MHz H nmr spectrum of X  Me,Sn  Cl  SnMe  137  3  CO.Me  A  _A  I  The 400 MHz H nmr spectrum of  (137)  3 Fig.  1:  (146)  2 X  - 55  Me Sn  C0 Et  3  H  the  H  80A  at  2  77  In f a c t ,  lower f i e l d  3  C0 Et  Me  i t seems apparent t h a t the 7-proton o f  (E) isomers ( i n which the Me3Sn group and  resonate the  3  E  i n compound ( 7 7 ) .  SnMe  Me Sn  2  Me  2.07)  -  the  7-protons  are  cis)  than those o f the (Z) isomers due, perhaps, t o  d e s h i e l d i n g e f f e c t o f the t i n atom.  N e v e r t h e l e s s , t h i s t r e n d , which  i s summarized i n T a b l e I I I , enables one t o d i s t i n g u i s h between a p a i r o f geometric isomers (78) and (83). The c h e m i c a l s h i f t s o f the two 9-proton s i n g l e t s (Sn^Me3))  of  the  (Z)  isomers  (83)  were  (5 (Sn Me3)) and A  a s s i g n e d t o the r e s p e c t i v e  t r i m e t h y l s t a n n y l groups on the b a s i s o f the f o l l o w i n g e v i d e n c e . nOe  difference  III),  as was  (-OMe) the  performed on compound (137)  described e a r l i e r ,  caused  high f i e l d  SnMe3  experiment  enhancement signal.  i r r a d i a t i o n o f the  T h e r e f o r e , t h i s resonance was  two  case, the resonance a t h i g h e r f i e l d was  the  6  at  9-proton  assigned (137)  the 3  in  the  That i s , i n each  a s s i g n e d to the t r i m e t h y l s t a n n y l  function.  the  two  9-proton s i n g l e t s o f the (E) isomers (78) were a s s i g n e d  evidence.  to A  On  respective  3.70  (5(Sn Me )).  singlets  ( T a b l e I I I ) were d e s i g n a t e d a c c o r d i n g l y .  group a t o the e s t e r  an  ( e n t r y 9, T a b l e  singlet  group on the a carbon o f the u n s a t u r a t e d e s t e r  isomers  In  o f the 9-proton s i g n a l t h a t c o r r e s p o n d e d to  By analogy, the c h e m i c a l s h i f t s o f the (Z)  (S  o t h e r hand, the c o r r e s p o n d i n g c h e m i c a l s h i f t assignments o f  trimethylstannyl  groups  on  the  basis  to  the  of  the  following  I n the n e x t c h a p t e r o f the d i s c u s s i o n ( I I I . A )  the  formation  - 56 -  Me Sn  C0 R'  3  2  H R  E 80  of  trisubstituted  discussed.  vinylstannanes  of  general  structure  (80) w i l l be  The trimethylstannyl group and the ester function  compounds  in  these  are cis—related, as i s the case i n the (E) isomers (78).  chemical s h i f t of the 9-proton singlet  (SnMe3  group)  of  each  The  of  the  compounds (80) was found to correspond closely to that of the high f i e l d Me3Sn s i n g l e t of the two 9-proton singlets Consequently,  of  (E)  isomers  (78).  by analogy, the resonance at higher f i e l d was assigned to  the trimethylstannyl group on the 6 carbon (78)  the  of  the  unsaturated  esters  (5(Sn Me )). B  3  A  tool  that further corroborated the stereochemical assignments of  the two geometric isomers, (Tables  IV  and  V).  (83)  and  (78),  was  1 3  C  nmr  spectroscopy  I f one considers the selected chemical s h i f t data  presented i n Table IV, the most s t r i k i n g feature to note  is  the  large  difference i n the chemical s h i f t s observed for the carbonyl carbons of a given p a i r of geometrically 2-alkenoates.  For  isomeric  instance,  alkyl  2,3-bis(trimethylstannyl)-  for the methyl 2,3-bis(trimethylstannyl)-  2-butenoates (entry 1) the chemical s h i f t s of the carbonyl carbons (5C^, Table  IV)  are  6  159.8  difference of 21 ppm. show  a  similar  ((Z)  isomer)  and  S  Most of the Isomeric pairs  difference i n chemical s h i f t .  (10.6 ppm) i s observed for the isomeric p a i r tert-BuMe2Si0CHo-).  180.8  The  listed  ((E) isomer), a in  The smallest  given  in  entry  Table  IV  difference 5  (R  =  chemical s h i f t s of the carbonyl carbon of the  -  T a b l e IV:  Selected (83)  57 -  C nmr c h e m i c a l s h i f t  1 3  A C0 R'  Me Sn 3  2  R D  S  nMe  data f o r compounds (78)  Me Sn  SnMe  3  R  3  D  78  C  83  0  2  R  and  3  '  A  Chemical s h i f t «(C ) «(C ) <(C ) 8  Entry  1  R  He  R'  Configuration  Compound  Et  Z E Z E Z E Z E Z E Z E Z E Z E Z E  124  2  Et  He  3  i-Pr  He  4  tert-BuMe SiOCH;(CH >  5  j p _ x - BuMe 2 S i OCH2  Et  6  (3-cyclohexenyl)methyl  He  7  CH -CHCH CH  He  8  CH -C(Br)CH (CH )3  He  9  C1CH CH CH  He  10 11  2  2  2  2  2  2  2  2  2  2  2  2  BrCH (CH ) 2  2  He  He  BrCH (CH >3 2  3  He  4  z  E  Z E  77 125 147 126 148 128 150 130 152 132 154 133 155 134 156 137 146 140 157 141 158  A  159. 8 1 8 0 . .8 166. 8 185 .6 1 7 0 . .9 1 8 4 . .2 1 6 5 . .3 1 8 4 . .4 1 6 6 . .1 1 7 7 , .7 1 6 3 . .7 1 8 4 . .2 163 .2 1 8 2 . .3 1 6 4 . .8 1 8 3 , .8 1 6 3 , .2 1 8 2 . .3 1 6 4 , .4 1 8 3 . .5 1 6 4 . .8 1 8 3 . .9  B  1 4 9 . .9 1 4 4 . ,2 1 4 8 . .2 1 4 3 . .4 146, 6 1 4 3 , .7 1 4 8 , .8 143, 8 1 4 7 , .1 1 4 4 . .9 1 4 9 . .9 1 4 4 , .7 1 4 9 , .6 1 4 4 , .6 1 4 9 . .2 1 4 4 , .2 150. 8 1 4 5 . .5 1 4 7 . .7 1 4 4 . .6 1 4 9 . .2 1 4 4 . ,1  C  171 .7 1 7 1 , .6 1 7 2 , .3 172 .2 1 7 2 , .8 1 7 2 , .7 172 .3 1 7 2 , .2 171 .6 171 .9 172 .4 171 .7 172 .1 1 7 2 , .1 1 7 2 , .2 1 7 2 , .1 1 7 2 , .1 172 .0 172 .1 172 .0 172 .1 172 .1  «(C )  b  D  26 .3 2 8 , .2 34, .0 34, . 5 4 0 , .3 4 3 , .1 4 0 , .9 4 1 . .6 6 8 , .0 6 9 . .9 4 7 . ,7 4 7 . .7 4 0 . .3 40. 8 40. 6 41. 3 4 4 . .4 4 4 . .3 39. 8 4 0 . ,7 4 0 . .6 40. 4  «(SnMe ) 3  -7 2, -5 • 9, -6 • 8, -6 • 1, -6 . 3 , -4 • 4 , -6 . 8 , -6 . 1 . -6 . 5 , - 6 0, - 6 . 6, - 5 . 5, -6 8, - 6 .• 0 , - 6 .• 7 , - 6 , 0, -6 7, - 6 , 0, -6 8, - 6 . 0, - 6 . 8, - 6 . 0.  Chemical s h i f t (6) was measured r e l a t i v e t o the d e u t e r i o c h l o r o f o r m s i g n a l (5 7 7 . 0 ) i n ppm. A l l s p e c t r a were r e c o r d e d on d e u t e r i o chloroform s o l u t i o n s . 6 0  o"(C ) ester D  r e f e r s t o the c h e m i c a l s h i f t function.  o f the a l l y l i c  carbon 7 to  the  - 6 .8 - 6 .7 - 6 .7 - 6 .6 - 4 , .5 - 6 .2 - 6 .7 - 6 , .6 - 5 .8 - 6 , .1 - 6 . ,5 - 6 , .2 - 6 . ,7 - 6 . .5 - 6 . .7 - 6 . .5 - 6 . .7 - 6 . ,4 - 6 . .7 - 6 . .5 - 6 . ,7 -6. 5  - 58 (Z)  isomers appeared i n the range 159-171 ppm, while for the (E) isomers  the range was 177-186 ppm.  As such, the stereochemical configuration of  a p a i r of geometric isomers could be v e r i f i e d by comparing the  chemical  s h i f t s of the carbonyl carbons. Upon  comparison  with  the  nmr chemical s h i f t s of the v i n y l i c  carbons of methyl (E)-2-butenoate,^ vinylic  the  high  field  of  the  carbons of the geometric isomers (83) and (78) were assigned to  the carbon (5(Cg)) alpha to the ester function. the  signals  chemical  shift  of  the  latter  It can  carbon  be  (5(Cg))  approximately 5 ppm i n going from the (Z) isomer (83)  noted  that  decreased  to the (E)  by  isomer  On the other hand, the chemical s h i f t of the carbon ( 5 ( C Q ) ) beta  (78).  to the ester remained r e l a t i v e l y unchanged. The two  signals due to the two 3-carbon singlets  trimethylstannyl  groups  IV)  the  chemical  to  the  of both the (E) and (Z) isomers appear at  high f i e l d r e l a t i v e to tetramethylsilane (Table  corresponding  all  cases  s h i f t s are at approximately -6.0 ppm.  These  signals were not assigned to s p e c i f i c  (TMS).  Thus,  trimethylstannyl  in  groups  of  the  compounds (78) and (83). Table V contains a summary of tin-carbon coupling constants observed in  the  range The  nmr spectra of compounds from  ^J.sn-C  the J.Sn-C 2  latter  one bond coupling (^isn-c)  v  a  l  a  n  d  cases  unresolved.  (78)  u  e  s  a  r  e  a  ^Sn-C  v  o  t  (83).  ^  hond coupling ( J.Sn-c) •  i r e e  These  constants 3  average of the H^Sn and ^-^Sn signals, whereas  n  a  t  and  l  u  e  s  refer to the H S n signal,^1 since i n these 9  the  centres  of  The  largest  tin-carbon  coupling through one bond.  the  H^Sn  a n  d  coupling  H7g  n  satellites  constants  occur  Thus, these values range from 326 to 346  are for Hz  - 59 Table V:  Selected  1  3  C nmr J v a l u e s f o r compounds (78) and (83)  Me Sn 3  \£J/ / \  R D  C0 R'  Me Sn  2  SnMe  3  SnMe  W A i \  RD  3  3  C0 R' 2  A  78  83  •ISn-C ( » - )  R  Intry  R*  1  Me  Et  2  Et  Me  3  i-Pr  Me  ££i£-BuMe Si0CH (CH )3  Me  5  tert-BuMe2S10CH3  Et  6  (3-cyclohexenyl)methyl  Me  7  CH -CHCH CH  Me  S  CH -C(Br)CH (CH )  9  C1CH CH CH  10  BrCH (CH )  11  BrCH (CH >4  2  2  2  2  2  2  2  2  2  2  2  2  2  2  3  Me  2  Me  3  Me  2  Configu- Com- < iSn •Me)* ration pound  Me  ( iSn-C ) 2  l  Z E Z E Z E Z E Z E Z E Z E Z E Z E Z E Z E  124 77 125 147 126 148 128 150 130 152 132 154 133 155 134 156 137 146 140 157 141 158  326, 344, 338, 342, 340, 340, 338, 343, 345, 345, 340, 342, 339, 344, 338, 341, 337, 346, 342, 341. 342, 343,  342 339 332 340 337 337 331 332 337 332 331 340 332 340 330 340 333 341 327 340 326 342  coupling between the t i n atom and the neighbouring carbon of a methyl group.  "'isn-C D  coupling between the t i n atom of a fi-SvHe^ group and the a l l y l i e carbon 7 to the ester function.  iSn-C  coupling between the t i n atom of an Q-SnMe3 group and the a l l y l i c carbon 7 to the ester function.  3  : D  3  iSn-C  : D  '  3  n  C  ( iSn 3  71 62 68 57 65 59 66 55 76 61 65 53 66 55 66 55 66 55 66 54 66 55  6 7 13 13 8 8 6 6 7 7 7 7 7 7 7 7 8 7  coupling between the t i n atom of a 0-SnMe3 group and the carbon adjacent to the a l l y l i c carbon ( C ) . D  Me,Sn  MejSn  C0 R*  iSn-C ' n  3  Me Sn  2  Co 3  ( iSn-C )  62 62 57 57 52 51 55 55 35 41 53 53 55 55 55 55 55 55 55 54 54 55  '^Sn-Me-  :  b  n  3  SnMe  3  iSn-C  n  (ii*)  ^  °D 2  2sn-C  M  e,Sn  SnMe  3  Cp 3 n  C0 R' 2  iSn-C (iI£H£) D  C  5 7 0 0 0 3 6 9 0 9 6 3 0 9 8 0 1 6  - 60 -  (Table  V).  There seems to be l i t t l e c o r r e l a t i o n between the  o f the *";Isn-C and  a  n  d  t  The  (83).  b  s t e r e o c h e m i c a l c o n f i g u r a t i o n o f the  e  ""^Sn-C  values  magnitude to those r e p o r t e d by  that  magnitude  isomers  appear i n T a b l e V are o f  Mitchell  for  4 3 b  (78) similar  (Z)-1,2-bis(trimethyl-  s tannyl)-1-alkenes. Also  of interest  i n Table V  c o n s i s t e n t throughout a l l ( t r a n s ) > ^J_sn-Cjj ( c i s ) . entry  1,  the  isomers,  "\lsn-C  6  respectively.  ^-Sn-Cp ^  n  t  b  (2)  e  a n  the ^J_Sri-C  For example,  2  A feature  are 71  that  Jsn-C^  i n the p a i r o f isomers g i v e n and  This difference  d  values.  n  examples p r e s e n t e d i n T a b l e V i s  values  n  are  62 Hz,  for  i n magnitude  ( £ ) isomers i s apparent  the  (Z)  (-10  for a l l  and  Hz)  sponding  Interestingly,  to the  (E)  the ^ i s n - C ^ ( c i s )  isomer)  are equal to  examples l i s t e d i n T a b l e V a p a r t from the and 5. the  F o r the  value  (E)  isomer (152)  of ^J.Sn-C  l  s  6  the  (E)  cases p r e s e n t e d  2  (i.e.  J_sn-C  n  effect  However, isomer  that  affects  the  values for  5 (R =  given i n entry  T a b l e V are the  isn-C  all  the J_Sn-Cjj 2  3  tert-BuMe Si0CH ) 2  value  2  i s 41 Hz. some  elec-  magnitude o f the c o u p l i n g c o n s t a n t s .  the r e a s o n f o r the anomaly t h a t appears i n the case o f the (148)  a  those c o r r e -  O b v i o u s l y i n t h i s l a t t e r case the a l l y l i c oxygen atom e x e r t s tronic  of  isomers g i v e n i n e n t r i e s  given i n entry whereas  1  n  values  (E)  between  i n T a b l e V and, thus enables one to d i s t i n g u i s h the c o n f i g u r a t i o n given p a i r .  in  3 (R = i.-Pr) i s not c l e a r .  ' v a l u e s , which are s m a l l ,  A l s o o f note  (E) in  g e n e r a l l y l e s s than 9  Hz. A  further  unexpectedly, isomers  f e a t u r e to  note i n T a b l e V  are the  2  J.Sn-C  n  values.  these v a l u e s are the same f o r any g i v e n p a i r o f  regardless  of  the  stereochemical  configuration.  Not  geometric This  is  - 61 Me Sn  SnMe  3  3  CO. Me  a  I|IIII]M 200  i ] l i T i | i r n ]•—i I'TTT i T i ] i T i i i i 11 i | i i i i | i i i i | n I 1 160 | !1 140 120 100 60  i i | i T i i | i i i i tT r r f | i i i i | IT-T T ] TT'1 I | 11 i i | i i i i | i i  60  40  20  0 PPM  ISO  If*"  F i g . 3:  The 75.6 MHz  1 J  C nmr and APT spectra of (141)  62 Me Sn  C0 Me  3  2  SnMe, a — b  A  i  a  I  200  F i g . 4:  T  rrp IbO  140  I  I  The 75.6 MHz  rp-r-  100  i i i i | i r i • T" 60 60  *0  I  1 J  C nmr and APT spectra of  (158)  20  0  P?u  - 63 -  apparent  in a l l  cases presented i n  isomers g i v e n i n e n t r y The  1 3  note  (83)  was  of 1 1 9  1 1 9  o f the  1 3  (Z)  S n nmr s p e c t r o s c o p y isomers  were  6 1  (Table V I ) .  configuration  going  from a (Z)  (128)  entries  2  and  and  s i g n a l s i n the  (E)  isomers  are  they  562  3.  is  the  to an (E)  the  Hz f o r the  approximately  (E)  In  apparent  c o m b i n a t i o n o f ^H,  1 3  C  and  1 1 9  l  u  e  feature  the  ^isn-Sn  *-  s  3  3  4  H  z  f°  Such a isomers  for  r  t  (E)  The former c h e m i c a l listed  5 (E - 1 - P r ) . to  illustrate  in The the  tin (Z)  shift  Table 1 1 9  e  given  6* -50 ppm, w h i l e i n the  isomers  b  large  the c h e m i c a l s h i f t s o f the two  i n a p a i r o f geometric i s apparent  a  f o r the p a i r o f  isomer g i v e n by e n t r y  conclusion, i t  v  that  F o r example,  isomer (150).  6 -36 ppm.  o f the  in  configuration.  isomers are a p p r o x i m a t e l y  (E)  and  stereo-  A striking  difference  s p e c t r a d e p i c t e d i n F i g u r e s 5 and 6 serve differences  the  corrobor-  i n a s s i g n i n g the  1 the ^J_Sn-Sn  Furthermore,  v a l u e s are c o n s i s t e n t f o r a l l for  pertinent  Although only three p a i r s  of a given p a i r of isomers.  o f isomers g i v e n i n e n t r y  isomer  except  is  s t u d i e d the r e s u l t s o b t a i n e d i n d i c a t e  i n c r e a s e o f over 200 Hz i s a l s o apparent by  It  illustrate  c o n f i g u r a t i o n a s s i g n e d t o the isomers (78)  o f the d a t a summarized i n Table VI  the p a i r  of  C nmr d a t a which appears i n  S n nmr s p e c t r o s c o p y can be used e f f e c t i v e l y  in  pair  s p e c t r a l t o o l which was used i n a few examples to  geometric  values  the  s e c t i o n was determined by the APT t e c h n i q u e .  stereochemical  chemical  from  s e c t i o n o f the t h e s i s .  t h a t the m u l t i p l i c i t y  A final the  apart  5 (R — tert-BuMeoSiOCrfo).  discussed i n this  experimental  ate  V  C nmr s p e c t r a d e p i c t e d i n F i g u r e s 3 and 4 serve to  the f e a t u r e s to  Table  VI  S n nmr  distinct  isomers.  from the p r e c e e d i n g d i s c u s s i o n t h a t a  S n nmr s p e c t r o s c o p y can p r o v i d e c o n c l u s i v e  - 64 Table VI:  1 1 9  S n nmr data for compounds (78) and (83)  Me Sn  Me Sn  C0 R'  3  H  R  SnMe  H  R  3  R'  R  3  C0 R' 2  83  78  Entry  SnMe  3  2  ConfiguComration pound  6"(SnMe3>  a  ( ^Sn-Sn) 3  1  tert-BuMeoSiOCHo(CHo)3  Me  Z E  128 150  -37. .2, -51. 5,  -36. .4 -50. ,1  334 562  2  C1CH CH CH  2  Me  Z E  137 146  -35, .4, -50. 2,  -35. .3 -49. ,3  317 527  3  BrCH (CH )  4  Me  Z E  141 158  -36, • 9, -36. .0 -51. 5, -50. .5  330 558  4  Et  Me  E  147  -51. 1,  -50. 7  562  5  i-Pr  Me  E  148  -60. 2,  -44. ,5  572  6  tert-BuMeoSiOCHo  Et  E  152  -48. 8,  -47. ,1  510  7  CH =CHCH CH  Me  E  155  -51, .6,  -51. ,0  551  8  (3 -cyclohexenyl)me thy 1  Me  E  154  -51. .8,  -50. ,2  564  2  2  2  2  2  2  2  Chemical s h i f t (5) was measured r e l a t i v e to the Me Sn signal (6 - 0) i n ppm. A l l spectra were recorded on deuteriochloroform solutions. 4  J i s measured i n Hz and represents coupling between  1 1 9  S n and  1 1 9  Sn.  - 65  F i g . 6:  The 111.8 MHz  F i g . 5:  The 111.8 MHz  1 1 9  -  S n nmr spectrum of (158)  l l s  S n nmr spectrum of (141)  - 66 evidence for the stereochemical configuration of a l k y l (E)- and (Z)-2,3bis(trimethylstannyl)-2-alkenoates.  C.  Preparation of  (E)-N.N-dimethyl-2.3-bis(trimethylstannyl)-2-  alkenamides  On the basis of internal  alkynes  the t r i p l e bond catalyzed  the  work  containing (e.g.  described  above,  a,B-acetylenic  esters)  addition of hexamethylditin.  withdrawing group.  u t i l i z i n g a,B-acetylenic  is  evident  that  an electron-withdrawing group attached to undergo  facile  Pd(0)-  It was of i n t e r e s t to probe the  p o s s i b i l i t y of using other i n t e r n a l alkynes that electron  it  are  activated  by  an  As a preliminary study, the p o s s i b i l i t y of  N,N-diethylamides was examined.  Thus, to a solution of N,N-dimethyl-2-butynamide (166)  i n 20  mL of  THF was added 1 equiv of hexamethylditin and 0.01 equiv of (PPl^^Pd and the mixture was s t i r r e d at room temperature. had  been  stirred  for  44  After the reaction mixture  h, glc analysis of an aliquot indicated the  appearance of a new peak and the absence of the signal corresponding the  with  1:1  petroleum ether-ethyl acetate) of the mixture indicated the presence  of  two 0.95) the  amide  (166).  Tic  analysis  (silica  major components (Rf — 0.36 and 0.60) corresponding to hexamethylditin. two  major  gel,  development  to  and one minor component (Rf =  After removal of  the  solvent,  products were separated by column chromatography of the  crude mixture on s i l i c a gel to afford two  different  oils.  compound (80% of the product) was subsequently i d e n t i f i e d as  The  major  (Z)-N.N-di-  - 67 methyl-2,3-bis(trimethylstannyl)-2-butenamide compound  (20%  of  (168)  Me Sn CONMe  — H  2  Me  166  Me Sn  3  •  CONMe  interpreted.  absorptions at frequency  H  Me  2  of  1620  cm' , 1  The  ir  compounds  spectra  attributable  the  S  n  .  H  groups.  ( Isn-H " 2  rocking  The  1  5  4  H z  ) •  a  the  ( J_s -H 2  resolution  =  5  3  Hz  n  broad 6-proton singlet at S 2.92. high  frequency  ( J_Sn-H ~ ^ 2  3-proton singlet at 5 1.94  a 3-proton singlet at 6 2.05  data,  stretching  of  2.91  ( J_sn-H 3  and  6  4  =  the (167)  ^z) 4  5  and H z  '  2.95.  In  nmr spectrum of the (E) isomer (168) consisted of two  9-proton singlets at 5 0.12 Hz),  (168)  H nmr spectrum of the (Z) isomer  - 11 Hz) and two 3-proton singlets at 6  contrast,  and  carbonyl  consisted of two sharp 9-proton singlets at 6 0.20  J  (167)  an a,B-unsaturated amide function, and absorptions at 775  trimethylstannyl  4  3  of both compounds showed  to  1  0.22  SnMe  168  and 770 cm" attributable to the tin-methyl  6  2  167  readily  minor  CONMe  3  The spectral data derived from the two were  the  (equation 26).  SnMe  3  =====  and  the product) was i d e n t i f i e d as (E)-N,N-dimethyl-2,3-  bis(trimethylstannyl)-2-butenamide  Me  (167)  mass  >  ("'j.Sn-H ~  a  n  4  6  d  In addition  spectrometry  °-  6  2  5  ( -Sn-H  ^z, J.Sn-H ~ 4  to  the  "  2j  1  1  above  5  3  ^z) and a spectral  v e r i f i e d that the molecular  formula for both isomers was C^2H270NSn2. Although d i r e c t evidence for the stereochemical configuration of the two  compounds  (167)  and  (168)  was  not  obtained,  there was enough  i n d i r e c t evidence to show that our assignments were correct.  The  over-  - 68 -  whelming  piece  of evidence,  o f c o u r s e , was the f a c t t h a t i n the  c a t a l y z e d a d d i t i o n o f h e x a m e t h y l d i t i n to the amide products  were  obtained.  Based  on  the  earlier  (Z)-2,3-bis(trimethylstannyl)-2-alkenoates would  predict  (168) isomer  (167).  Indeed,  in_  situ  when a s o l u t i o n o f the  (E)  Me Sn  SnMe  H  3  Me  isomer  2  showed  very  the  two  example,  the  (Z)  i n THF  (equation  27).  (27) SnMe  3  isomers  (167)  and  (168)  s i m i l a r to the ^H nmr s p e c t r a o f methyl (E) - and  (Z)-2,3-bis(trimethylstannyl)-2-butenoates For  of  168  the ^H nmr s p e c t r a o f  patterns  (E) isomer  2  Me  CONMe  one  CONMe 1  H  1.5h  alkyl  had c o m p l e t e l y  (168)  3  THF.A  1 67 Furthermore,  the  (167)  Me Sni  3  that  (Z) isomer (167)  isomerized  corresponding  isomeric  unstable,  isomerization  indicated that  the  finding  and (168),  was r e f l u x e d f o r 1.5 h , t i c a n a l y s i s to  two  are t h e r m a l l y  t h a t o f the two p r o d u c t s (167)  had a r i s e n as a r e s u l t o f  (166)  Pd(0)-  (77)  i n the ^H nmr s p e c t r a o f the  and (124),  (Z) isomers  respectively.  (167)  and (124),  the two 9 - p r o t o n s i n g l e t s due to the t r i m e t h y l s t a n n y l groups appear v e r y close  together  hand, two  (AS  =  0.02  and 0.03 ppm, r e s p e c t i v e l y ) .  i n the ^H nmr s p e c t r a o f the two (E) isomers (168)  On the  and  other  (77) ,  the  c o r r e s p o n d i n g 9 - p r o t o n s i n g l e t s appear f u r t h e r a p a r t (AS = 0.13 and  0.09, groups  respectively). in  the  sponding s i g n a l s  Moreover,  the  resonances  the  vinyl  methyl  two (Z) isomers are a t h i g h e r f i e l d than the two c o r r e o f the two (E) i s o m e r s ,  A l t h o u g h the P d ( 0 ) - c a t a l y z e d a d d i t i o n acetylenic  of  N , N - d i e t h y l a m i d e s (169)  respectively. of  hexamethylditin  to  was not i n v e s t i g a t e d e x t e n s i v e l y  a,8it  - 69 was found to be a r e l a t i v e l y f a c i l e (Table  VII).  It  should  be  noted  experiment summarized i n e n t r y 1, under  the s p e c i f i e d  groups  (entries  1,2),  examples  and 4 ) ,  THF,  o n l y the  a  4)  3  cases  examples  number  (E) isomer  (Table  involving  The  pathway  a,^-acetylenic  of  follows (or  silyl  Although,  in  a,^-acetylenic  when  compared  esters  agreement w i t h the a s s i g n e d  corre-  (Table 1).  In a l l  (169)  were  structures.  to  afford  the  20).  The  are  It  is  evident  less  corresponding i s most  subsequent  likely  isomerization  23  from the p r e c e e d i n g d i s c u s s i o n t h a t  the  stable  than the  esters  group as d e p i c t e d i n s t r u c t u r e s depicted  to  to t h a t d e p i c t e d i n e q u a t i o n  (90).  can be a t t r i b u t e d to the g r e a t e r s t e r i c  expected  products  compounds i n t o the c o r r e s p o n d i n g (E) isomers p r o b a b l y  c o r r e s p o n d i n g a,B-acetylenic  as  two  to  (Z) isomers o b t a i n e d from the c o r r e s p o n d i n g a,B-acetylenic  group  last  f o r the P d ( 0 ) - c a t a l y z e d a d d i t i o n o f h e x a m e t h y l d i t i n  latter  (166)  the  the r e a c t i o n s were performed i n r e f l u x i n g  a m e c h a n i s t i c pathway analogous  amides  present  p r i m a r y bromide ( e n t r y 3) and a VII).  N,N-dimethylamides  Scheme  isolated  were  to t h a t d e p i c t e d i n Scheme 19.  these  was  the  addition  (Z)-N,N-dimethyl-2,3-bis(trimethylstannyl)-2-alkenamides analogous  amides  except f o r  (170)  ( T a b l e V I I ) the ^H nmr, i r and mass s p e c t r a o f the  found to be i n complete  of  The f u n c t i o n a l groups  r e a c t i o n times were c o n s i d e r a b l y l o n g e r  sponding  a  t h a t were t o l e r a t e d d u r i n g the  ether f u n c t i o n (entry (entries  for  t h a t i n each c a s e ,  reaction conditions.  i n the s t a r t i n g m a t e r i a l s alkyl  process  in  (177)  structure  N,N-dimethy1-  (Z) isomers o b t a i n e d from the This difference  in  stability  i n t e r a c t i o n imposed by the amide  and (177A) vs t h a t  (178).  of  As a consequence,  the  ester  i t would be  t h a t the energy r e q u i r e d f o r the i s o m e r i z a t i o n p r o c e s s  to o c c u r  - 70 Table VII:  Conversion of a,/9-acetylenic N,N-dImethylamIdes (169) into (E)-N,N-dimethyl-2,3-bis(trimethylstannyl)-2-alkenamides (170)  Me Sn  CONMe  3  •CONMe,  H  R  169  Entry  2  i 7  S  n  Reaction conditions (°C/h)  169  166  c  171  c  e  3  3  170  Yield  Me  20/44  168  13  Et  20/72  174  48  67/26  175  75  67/48  176  63  172*  BrCH CH CH2  173  ;t^rt-BuMe SiOCH CH CH  c  M  0  2  2  2  2  2  2  (%)  b  c  Reactions were performed i n solutions of THF u t i l i z i n g approximately 0.01 equiv of (PPt^^Pd and approximately 1 equiv of MegSn . 2  Y i e l d of i s o l a t e d ,  d i s t i l l e d product.  These materials were prepared by Dr. J . M . C h o n g .  42  50% of the corresponding (Z) Isomer was also i s o l a t e d . We thank Dr. J . M . Chong for a sample of this m a t e r i a l .  - 71 -  in  (Z)-N,N-dimethyl-2,3-bis(trimethylstannyl)-2-alkenamides  (167)  would  be  less  than  that  r e q u i r e d f o r the c o r r e s p o n d i n g  (Z)-2,3-bis(trimethylstannyl)-2-alkenoates rate  of  a,8-acetylenic a,8-acetylenic  III.  (83).  The  i s o m e r i z a t i o n i s borne out e x p e r i m e n t a l l y .  the P d ( 0 ) - c a t a l y z e d  addition reaction i s  esters  lead  to  such  in  refluxing  (Z) isomers,  N , N - d i e t h y l a m i d e s l e a d to the c o r r e s p o n d i n g  Chemistry o f a l k y l  ( Z ) - and  alkyl the  For i n s t a n c e , when  performed  the c o r r e s p o n d i n g  difference i n  as  (E)  THF,  whereas isomers.  (E)-2,3-bis(trimethylstannyl)-2-  alkenoates  A.  Transmetalation intermediates  o f the t i t l e  compounds and r e a c t i o n o f the r e s u l t a n t  with e l e c t r o p h i l e s  Having e s t a b l i s h e d an e f f i c i e n t and  f a c i l e r o u t e f o r the  of a l k y l 2,3-bis(trimethylstannyl)-2-alkenoates, to determine whether or not these in  synthesis.  Chong ! 2  had  a program was  substances c o u l d be  shown  that  (E)-2,3-bis(trimethylstannyl)-2-butenoate  the (77)  preparation  used  o-SnMe3 could  initiated effectively  group o f e t h y l be  removed  - 72 s e l e c t i v e l y by transmetalation with methyllithium and that the resultant n u c l e o p h i l i c intermediate reacted with a v a r i e t y philes  to  afford  consequence, compounds  trisubstituted  of  vinylstannanes  reactive  (equation 11).  our i n i t i a l objective i n probing the u t i l i t y of  in  synthesis  metalation  reaction  alkenoates  that  was  by  electroAs a  the  title  to determine the generality of the trans-  employing  alkyl  2,3-bis(trimethylstannyl)-2-  possessed different functional groups and to determine  the r e a c t i v i t y of the resultant nucleophilic intermediates  by  treating  them with a v a r i e t y of e l e c t r o p h i l e s . The  conditions  under  which  the transmetalation reaction was per-  formed i s i l l u s t r a t e d by the following example. methyl  Thus,  (Z)-2,3-bis(trimethylstannyl)-2-pentenoate  a  (125)  solution in  treated with a s o l u t i o n of methyllithium i n ether at -98°C for  of  THF was 15  min.  3-Iodopropene was added and the solution was s t i r r e d at -98°C for 30 min and at -78°C for 45 min. isolated  as  the  After appropriate workup, the ester (179)  sole substitution product i n 85% y i e l d (equation 28).  Me Sn  SnMe  3  Me Sn C0 Me 1.MeLI,THF,-98°C \ = / 2. CH CHCH I / \ / -98° — -78°C  3  3  2  C0 Me 2  125  Determination accomplished  of by  3  the  to  analysis  an  "  of  2  179  H +  the  singlet  a l l y l group.  (28)  2  constitution  presence of one 9-proton corresponding  was  of ^H  compound nmr  (Me3Sn  (179)  was  readily  spectrum, which showed the  group)  as  well  as  signals  These l a t t e r signals consisted of a  2-proton dt at 6 3.21 (J •= 6, 1.5 Hz), a 1-proton ddt at fi 4.97  (J - 17,  - 73 2,  1.5 Hz), a 1-proton ddt at 6 4.98  ddt at 6 5.87  (J - 17, 10, 6 Hz).  (J = 10, 2, 1.5 Hz) and a 1-proton  Furthermore,  high  resolution  mass  spectrometry confirmed that the molecular formula was C^2l^24 2^^2 * 0  The  results  of reactions involving the use of other a l k y l  (trimethylstannyl)-2-alkenoates and a v a r i e t y of a l k y l a t i n g summarized  in  Table V I I I .  from 40% to 81%, although optimized.  2,3-bis-  agents  are  These reactions proceeded i n y i e l d s ranging in  some  cases  the  yields  have  not  been  A feature to note i n the results summarized i n Table VIII  that the y i e l d s of substitution products (80) were generally reactive a l k y l a t i n g reagents were employed.  (entries  3,  when  For example, the a l k y l a t i n g  agents 3-iodopropene (entries 15-17), iodomethane (entries 7, 3-iodo-2-methylpropene  good  is  11,  13),  8, 10, 14) and l-bromo-3-methyl-2-  butene (entries 5, 9, 12), gave good to excellent y i e l d s of the products (80).  In  all  of  these  experiments  involving  the  use of reactive  h a l i d e s , u n i d e n t i f i e d polymeric material was also present i n tions.  distillation, product.  thus  affording  the  by  direct  ester (80) as the sole substitution  On the other hand, i s o l a t e d y i e l d s of the substitution product  were  lower  when  less reactive halides (for example, l - c h l o r o - 3 -  iodopropane (entry 1) and 2,5-diiodo-l-pentene In  solu-  However, t h i s l a t t e r material was r e a d i l y removed from the crude  o i l by column chromatography of the mixture on s i l i c a gel or  (80)  the  (entry 4)) were employed.  these cases, glc analyses of the solutions indicated the presence of  varying amounts (up to 10%) of the corresponding products i n which E=H. Also  evident  upon  polymeric m a t e r i a l . those  cases  workup  was  a  higher  proportion of unidentified  Efforts were made to increase the product y i e l d s i n  involving  "unreactive" a l k y l a t i n g agents.  However, these  - 74  Table VIII:  T r a n s m e t a l a t i o n o f a l k y l (Z) o r (E)-2,3-bis(trimethyl s t a n n y l ) - 2 - a l k e n o a t e s ((83) o r (78)) and r e a c t i o n o f the r e s u l t a n t intermediates with e l e c t r o p h i l e s  Me Sn  SnMe,  3  Me Sn  «  R  C0 R'  3  H C0 R'  3  (83  or  78)  SnMe  C0 R"  -ir-H e  H R  2  M ,Sn  2  83  Entry  -  R  3  E  78  80  R  b  2  R'  EX  80  C  77  Me  Et  ICH CH CH C1  2  77  Me  Et  ClSlMe  3 4  77  Me  Et  77 77 77  Me Me  Et Et  ICH -CMe-CH ICH CH CH -CI-CH  Et Me  BrCH -CH-CMe BrCH -OC-SiMe3 IMe  184 185  Me  ICH -CMe-CH  e  187  68  BrCH -CH-CMe9 ICH -CMe-CH ^  188  71 74  IMe BrCH -CH-CMe  190 191  74 79 76 85  5 6 7  153  8  153  Me 2-(2-cyclopentenyl)ethyl 2-(2-cyclopentenyl)ethyl  9 10  153  2-(2-cyclopentenyl)ethyl  Me  152  t.ert-BuMe Si0CH  11  152  12 13 14  152 149 149  tert-BuMe SiOCH tert-BuMe SiGCH  15 16  125 126  17  133  2  Et  2  2  Et  2  2  2  Et Me Me Me  cyclopropyl cyclopropyl Et i-Pr CH -CHCH CH 2  2  2  2  2  3 e  2  2  2  2  2  2  f 2  2  2  2  2  2  2  2  2  IMe ICH -CMe-CH ICH -CH-CH  2  69  183  42 66  189  40 72  81  2  192 193 179  Me  ICH -CH-CH  2  194  73  Me  ICH -CH-CH  2  195  75  2  2  2  2  e 2  d  70  182  186  (%)  54  1  2  180 181  Yield  Reaction conditions: A s o l u t i o n ( T H F , - 9 8 ° C ) o f ( 7 8 ) o r ( 8 3 ) was t r e a t e d w i t h M e L i ( 1 . 2 e q u i v ) , t h e r e a c t i o n m i x t u r e was s t i r r e d a t - 9 8 ° C ( 1 0 - 3 5 m i n ) , t h e a p p r o p r i a t e a l k y l a t i n g a g e n t ( E X ) was a d d e d , t h e r e a c t i o n m i x t u r e was s t i r r e d a t - 9 8 ° C ( 3 0 m i n ) a n d a t - 7 8 ° C ( 4 5 m i n - 2 . 5 h ) a n d t h e n s a t u r a t e d a q u e o u s NH4CI was a d d e d . In a l l cases the given i n entries isomer (83).  s t a r t i n g m a t e r i a l was t h e ( £ ) i s o m e r ( 7 8 ) , except for 15-17. In each o f these c a s e s , the s t a r t i n g m a t e r i a l  the was  examples the (Z)  T h e s e m a t e r i a l s were p a s s e d t h r o u g h a column o f a c t i v i t y I b a s i c a l u m i n a i m m e d i a t e l y p r i o r t o u s e , w i t h t h e e x c e p t i o n o f l - b r o m o - 3 - m e t h y l - 2 - b u t e n e ( e n t r i e s 5 , 9 , 12) w h i c h was d i s t i l l e d i m m e d i a t e l y p r i o r t o u s e . Yield  of purified  distilled  product.  This  material  was s u p p l i e d b y D r .  I.D.  This  material  was  A . Yueng o f  supplied by Dr.  Suckling of our  our  laboratories.  laboratories.  - 75 -  e f f o r t s w e r e n o t s u c c e s s f u l . F o r i n s t a n c e , w h e n t h e t u r e  w a s  r a i s e dt o  0°C,  w h e n  t h e  o f p r o d u c ti nw h c i h  E = H .  e x p e r m i e n t s u m m a z r e i d i n e n t r y 1 w a s c a r r i e  0°C i n s t e a d o f a t -78°C, t h e  t e m  g l ca n a l y s i s o f a n a l i q u o t o f t h e s o  s h o w e d a n n ic r e a s e i n t h e p r o p o r t o in e x a m p e l ,  r e a c t i o n  p r o d u c ti nw h c i h  t h e g l c r a t i o o f t h e E = H  w a s  s u b s t i t u t i o n  p r o d u  a p p r o x m i a t e y l 1 : 1 .F u r t h e r m o r e , u  e n h a n c n ig t h e n u c l e o p h i l i c i t y o f t h e a n o in c i n it e r m e d a it e b y a d d n ig t ot h e  r e a c t i o n  m x it u r e ,t h e  p r o p o r t o in o f p r o d u c t i n w h c i h E = H  s l i g h t l y d e c r e a s e d , b u t t h e r e a c t i o n s a b s e n c e  w e r e  n o t  a s  c e l a n  a s  o f H M P A , a n d c o n s e q u e n t y l t h e y i e l d s w e r e o lw e r .I t s h o  m e n o i t n e d t h a t w h e n t h e e x p e r m i e n t s u m m a z r e i d b y  e n t r y6  w a s  o u t , g l c a n a l y s i s o f t h e s o l u t i o n i n d i c a t e d t h e p r e s e n c e ( u p t o t h e c o r r e s p o n d n ig p r o d u c t i n w h c i h E = H . t h e  c r u d e  H o w e v e r , u p o n c h r o m a o t g r a p  o i l o n s i l i c a g e l , t h e e s t e r ( 1 8 5 ) w a s o b t a n ie d a s  s u b s t i t u t i o n p r o d u c t .A t h lo u g h t h e y i e l d o f ( 1 8 5 ) w a s o lw , e f f o r t s n o t  m a d e  t o o p t m i z i e t h e r e a c t i o n c o n d i t i o n s . I t s h o u d l b e n o  i n o r d e r t o e n s u r e t h a t t h e t r a n s m e t a l a t i o n a l k y l a t i o n r e a c t i o n s p r o i na  c e la n  a n d e f f i c i e n t m a n n e r i t i s m i p e r a t v ie t o m a n it a n i m  f r e e c o n d i t i o n s a n d t o u s e m e t h y t i h lu im o f o l w h a l i d ec o n t e n t r e l a t i v e l y f r e s h l y o p e n e d  r  b o t t l e ( u p t o 1 m o n h t o l d ) . A l l c o m p o u  r e p o r t e d i n T a b e l V I I I e x h i b i t e d ^ H n m r , i r a n d  m a s  s p e c t r a  a c c o r d w t i h t h e a s s g in e d s t r u c t u r e s . R e g a r d e l s s  o f t h e  s t e r e o c h e m s i t r y o f t h e a l k y l 2 3 ,b i s ( t r i m e t h y l -  s t a n n y l )2a k le n o a t e e m p o l y e d f o r p r o c e s s , t h e  t h e  t r a n s m e t a l a t i o n a l k y l a t i o n  p r o d u c t p o s s e s s e d t h e s a m e s t e r e o c h e m s i t r y i n b o t h c  T h u s , t r e a t m e n t o f T H F s o l u t i o n s o f ( 7 8 )  o r( 8 3 )  w t i h  m e t h y  - 76 followed  by  a l k y l a t i o n of the resultant intermediate, provided i n both  cases, a single product i n which the ester group and the nyl  group  (83)  and (78)  anions  39  are  in  a cis relationship.  leads,  in  each  case,  trimethylstan-  Presumably, transmetalation of  to  the  formation  of  allenoate  (79) , which alkylate from the side opposite the bulky trimethyl-  stannyl group, thus affording a single stereoisomer Me Sn  SnMe  3  H  R 83 , ft  Me Sn  3  OR'  3  —  C0 'R'  (80)  Me Sn  (Scheme  21).  C0 R'  3  2  > — ( — H » 79  R  2  Me Sn  0  L  R  i  78 SnMe  CO,R'  3  H  R  80  E  Scheme 21  However,  one  might  expect  a lowering i n the s t e r e o s e l e c t i v i t y i f the  e l e c t r o p h i l e was s t e r i c a l l y undemanding, such as proton. the  intermediate  resulting  from  the  transmetalation  protonated, glc analysis of the solution  showed  geometrically  and  respectively  the 3  n  from  each  (196)  These other  latter by  two  analysis  proton  showed  of  (124)  presence  when was  of  the  (197), i n a r a t i o of  1:8,  products  were  readily  of t h e i r ^H nmr spectra.  i n each of the ^H nmr spectra, the signal  vinylic  ( Jg _jj).  products  (equation 29).  distinguished Explicitly,  isomeric  the  Indeed,  corresponding  to  s a t e l l i t e peaks due to tin-proton coupling  The coupling constant associated with this coupling i s 72  Hz  - 77 -  Me Sn  SnMe  3  Me Sn  3  H  3  H  Me Sn  H  Me  C0 Et  •  Me  2  124  3  tion  of  C0 Et  Me  2  196 1  Chong,  t r a n s  (196)  ^  >  H 8  Thus, based on the fact  stereochemical  4 2  configura-  was assigned as (E), whereas (197) was assigned as (Z).  transmetalation-protonation butenoate  >  ,29  197  ^J-Sn-H ( c i s ) , 4 3 a  had reported a product  42  2  H  i n compound (196) and 116 Hz i n compound (197). that J_Sn-H ^  C0 Et  3  of  ratio  of  1:9  ((196):(197))  ethyl  (E)-2,3-bis(trimethylstannyl)-2-  the  (77).  Up to this point i n the discussion no conclusive evidence presented  regarding  the  stereochemical  s u b s t i t u t i o n products (80). representative  example  However nOe  unequivocally  configuration of these compounds. (179),  for  irradiation  of  the  singlet  Me Sn  difference  in  at  been  configuration assigned to the  established  Thus,  has  6  the 3.73  experiments the  on  a  stereochemical  ^H nmr  spectrum  of  (-OMe) caused signal  C0 Me  3  2  179 enhancement of the s i n g l e t at 6 0.15 (-SnMe.3), while i r r a d i a t i o n of signal  at  6  (-CH CHCH ), 2  2  2.45 6  0.93  (-CH2CH3) caused (-CH CH ) 2  and  3  signal 6  0.15  enhancement (-SnMe.3).  at  6  the 3.19  Furthermore,  i r r a d i a t i o n of the s i n g l e t at 8 0.15 (-SnMe.3), caused signal enhancement at 6 0.93 (-CH CH ), 6. 2.45 (-CH CH ) and 6 3.73 (-OMe). 2  3  2  3  - 78 Since  it  seemed  l i k e l y that the transmetalation of a l k y l 2,3-bis-  (trimethylstannyl)-2-alkenoates anions,  an  anions.  Specifically,  anion  attempt  using  was  leads  made  to  formation  i n THF was treated with the  allenoate  provide evidence for such allenoate  tert-butyldimethylsilyl  by  of  attempts were made to d i r e c t l y trap an  ever, when a solution of ethyl  followed  the  various s i l y l a t i n g agents, such as  chloride and  (77)  to  allenoate  tert-butyldimethylsilyl  trifluoromethanesulfonate.  (E)-2,3-bis(trimethylstannyl)-2-butenoate a  addition  solution of  of  methyllithium  tert-butyldimethylsilyl  in  at  atures  corresponding  -78°C,  substituted allene (198) reactions  -48°C), was  no  isolated  (equation  different  30).  or  temperto  the  Although  the  were not clean, the. predominant material which was  was the corresponding product (197). crude  material  ether,  chloride  t e r t - b u t y l d i m e t h y l s i l y l trifluoromethanesulfonate (-98°C,  How-  identified  Furthermore, the i r spectra of the  o i l s showed no evidence of a carbon-carbon double bond stretching  frequency corresponding to an allene function. Me Sn  C0 Et  3  2  H Me  SnMe  \ f Me Sn  3  3  3  -  or TBDMSQTf  )—(  Me  77 Interestingly,  (77)  at - 9 8 ° C , and the reaction mixture was then  to  a  of the intermediate r e s u l t i n g from the transmetalation of  product  was  formed.  material was i s o l a t e d i n 70% that  !  2  though, when t r i m e t h y l s i l y l chloride was added  solution  indicated  OSIMe Bu 198  THF  unexpected  OEt  this  to  -78°C,  After appropriate workup, the  yield.  substance  warmed  Analysis  possessed  the  of  the  spectral  structure  an  latter data  depicted i n  - 79 molecular  formula  (199).  an a b s o r p t i o n a t 1695 frequency cm"  silyl  cm'  group.  the  attributable  1  o f an a , ^ - u n s a t u r a t e d  attributable  1  For example,  i r spectrum o f  to  the  (199)  carbonyl  showed  stretching  e s t e r f u n c t i o n and an a b s o r p t i o n a t  850  to the s i l i c o n - m e t h y l r o c k i n g frequency o f a t r i m e t h y l -  The  -^-H nmr  spectrum  Me Sn  of  (199)  consisted  of a 9-proton  C0 Et  3  2  H Me  SiMe  3  199 s i n g l e t at  ( J_sn-H 2  =  5  3  H z  ) >  a  ( J_Sn-H 3  =  Furthermore,  5  1  H  z  ^  high  a  n  d  a  2  "P  t  o  quartet at  n  of  (199)  5  of  2.22.  If  the e s t e r f u n c t i o n and the methyl group  would  expect the c o r r e s p o n d i n g c h e m i c a l s h i f t  the  chemical  to be a t a p p r o x i m a t e l y 5 2.1 W i t h a seemingly  of  a  (125) was  when the  7  see  -78°C,  the  evidence the  Hz). mole-  for  the  assignment 1  H  nmr  o f the v i n y l methyl group i s were  cis-related  5 we  o f the v i n y l methyl group  e n t r y 1,  Table  III).  o f t h i s method was i n v e s t i g a t e d . r e s u l t i n g from  the  such as However,  transmetalation  (Z)-2,3-bis(trimethylstannyl)-2-pentenoate  was t r e a t e d w i t h t r i m e t h y l s i l y l c h l o r i d e a t warmed to  =  method o f g e n e r a t i n g v i n y l s i l a n e s  intermediate  THF s o l u t i o n o f methyl  shift  ppm ( e . g .  efficient  a t h a n d , the g e n e r a l i t y  unexpectedly,  (J  Moreover, i n the  spectrum  (199)  4.12  was not o b t a i n e d ,  to t h a t o f compound (179).  (199)  3  (J = 7 H z ) , a 3 - p r o t o n s i n g l e t a t 6  Although conclusive  1 1 ,  configuration  was made by analogy  o  (-SiMe  r e s o l u t i o n mass s p e c t r o m e t r y v e r i f i e d t h a t  c u l a r f o r m u l a was C ^ r ^ C ^ S ^ stereochemical  r  6 0.25  9-proton s i n g l e t at  a 3 - p r o t o n t r i p l e t a t 6 1.30  group), 2.22  5 0.15  a substantial  amount o f  - 9 8 ° C and the  (201)  was formed  reaction (equation  - 80 31).  Glc analysis of the reaction mixture indicated the presence of an  85:15 mixture of products corresponding to (201) (equation 31).  SnMe  3  Me Sn  3  C0 Me  3  1.MeLI,THF  \ = /  ^  27TMSC1  f  C0 Me  d i f f e r e n t temperatures (-78 C, 6  that the r a t i o of (200)  to (201)  C0 Me  3  2  /  +  SIMe  (311 \  '  3  1  201  15  85  - 2 0 ° C , O'C, 25°C) i t was found  remained r e l a t i v e l y unchanged. Further-  changing the solvent to pentane or to a DME;THF (5:1)  not improve the  outcome  of  the  reaction  reaction was repeated using other a l k y l alkenoates  such as (150)  mixture of products  (equation  mixture did  31).  When  the  2,3-bis(trimethylstannyl)-2-  and (153), there was obtained, i n each case, a  analogous to those  similar ratio (glc).  1  H  200  -48°C,  analysis)  \ = /  \  '  2  Me Sn  2  =J  125  more,  respectively  When the reaction was c a r e f u l l y monitored (glc  Me Sn  at  and (200),  shown  in  equation  Presumably, when the a l k y l group ( i . e .  Me Sn  C0 Me  3  Me,STi  2  31,  in  a  R group) of  C0 Me 2  M SnMe BJMe SI0'  1  5  the alkyl-2,3-bis(trimethylstannyl)-2-alkenoates  (153)),  a  methyl  group  3  153  r \  0  2  demanding than that of  SnMe  J——'  3  becomes s t e r i c a l l y more  (compounds  (125),  (150)  and  .& competition arises between O - s i l y l a t i o n and C - s i l y l a t i o n . In  these l a t t e r cases O - s i l y l a t i o n would predominate  to  afford  compounds  analogous to (198), which, upon exposure to workup conditions would lead  - 81 to the observed products.  As such,  butenoate  only  (77)  was  the  ethyl  2,3-bis(trimethylstannyl)-2-  compound,  which, upon transmetalation-  s i l y l a t i o n , gave substantial amounts of v i n y l s i l a n e . The transmetalation-alkylation reactions discussed so section  in  this  have consisted of sequences involving intermolecular a l k y l a t i o n  processes.  We were also  corresponding  interested  intramolecular  in  probing  alkylation  methylstannyl)-2-alkenoates alkylation cyclic  of  the  resultant  anions,  202  would  have  served  I t was found that when a solution of stannyl) -6-iodo- 2 -hexenoate  (139)  methyllithium (ether solution)  In p a r t i c u l a r , we  (203)  as  (equation  32).  204  useful  intermediates  i n the  3  methyl  (Z)-2,3-bis(trimethyl-  i n THF was treated successively with  and HMPA (2.3 equiv) at  -98°C,  and  the  was then s t i r r e d at -98°C for 1 h, a single product was formed.  After appropriate workup, the l a t t e r material was i s o l a t e d i n 73% (equation  the  lead to the formation of  "  development of a new annulation sequence.^  mixture  of  (Z)-w-halo-2,3-bis(tri-  esters  203  compounds  utility  ((202) or (204)), followed by intramolecular  trimethylstannyl a,^-unsaturated  latter  the  reactions.  f e l t that the transmetalation of methyl (E)- or  These  far  33).  Determination  139  of the structure of t h i s material  205  yield (205)  - 82 was accomplished by analysis of the example, 0.16  the  ( J.Sn-H " 2  4- proton  5  5  Hz  nmr, i r and  mass  spectra.  For  nmr  spectrum of (205) showed a 9-proton s i n g l e t at S  )>  2-proton quartet at  a  5  1.87  (J  -  7  Hz),  a  t r i p l e t at 5 2.60 (J - 7 Hz) and a 3-proton s i n g l e t at 6 3.70.  Furthermore, high resolution mass spectrometry showed that the molecular formula of t h i s material i s CioHisC^SJn. The r e s u l t s of using other a l k y l w-halo-2,3-bis(trimethylstannyl)-2alkenoates expected,  are  summarized  in  Table  It should be noted, that as  the stereochemical configuration of the  consequence  in  the  cyclization  experiments summarized i n entries further  IX.  evidence  chemoselective alkenoates  that  the  1  and  reactive  transmetalation  are  process.  of  allenoate anions.  For 2.  substrate example,  These  is  of  no  compare the  examples  provide  intermediates r e s u l t i n g from the  alkyl  2,3-bis(trimethylstannyl)-2-  It may also be noted that the y i e l d s  of the reactions summarized i n Table IX are generally good, ranging from 58%  to  74%.  Although glc analyses of each of the reaction mixtures of  the experiments summarized i n Table IX indicated major  component  (90%),  tic  analyses  the  presence  of  one  indicated the presence of polar  baseline material corresponding to unidentified polymeric material. a  consequence,  the  i s o l a t e d y i e l d s of the c y c l i z e d compounds (203)  Table IX are not as high as one might expect. of  58%  (entry  6)  is  good  Nevertheless,  In contrast, the reactions  5- and 6-membered rings were e f f i c i e n t processes, y i e l d s of 69-74% (Table IX). IX  exhibit  the  in  yield  considering the fact that i t r e f l e c t s  formation of a 7-membered r i n g .  Table  As  leading  the to  proceeding i n i s o l a t e d  A l l the compounds that are  summarized  in  ^H nmr, i r and mass spectra i n f u l l accord with the  - 83 -  T a b l e IX:  Formation o f c y c l i c ^ - t r i m e t h y l s t a n n y l (203)  202  Entry  a,^-unsaturated  203  esters  204  202  204  n  X  203  Yield  146  -  1  Cl  205  69  2  -  138  1  Br  205  74  3  -  139  1  I  205  73  4  -  141  2  Br  206  72  5  -  142  3  I  207  58  l  3  c  Reaction conditions: t r e a t e d w i t h MeLi (1.2 m i x t u r e was stirred NH^Cl was added.  Y i e l d of p u r i f i e d ,  In  this  reaction,  (%)  A s o l u t i o n (THF, - 9 8 ° C ) o f (202) o r (204) was e q u i v ) and HMPA (2-3 equiv), the reaction at - 9 8 ° C f o r 1 h , and then s a t u r a t e d aqueous  distilled  product.  the r e a c t i o n m i x t u r e was warmed to  -78°C.  - 84 assigned structures. It should also be noted that the amide (208) was readily  formed  in  70% yield from the intramolecular transmetalation-alkylation of (E)-N,Ndimethyl-2,3-bis(trimethylstannyl)-6-bromo-2-hexenamide 34).  (175)  (equation  The spectral data derived from compound (208) are fully in accord  with the assigned structure.  (34)  175  208  In summary i t should be pointed out that, in order for the lecular  transmetalation-alkylation  reactions to proceed in a clean and  efficient manner, i t is imperative to use HMPA. is  not  intramo-  On the other hand, HMPA  required for the corresponding intermolecular transmetalation-  alkylation reactions.  B.  Synthesis of stereochemically defined trisubstituted vinyl iodides  With a facile synthesis of trisubstituted vinylstannanes of structure  (80)  at  hand,  our next objective was to u t i l i z e these com-  pounds as intermediates for developing a synthetic route to ized,  stereochemically  defined  transformation that we envisaged function  general  tetrasubstituted was  the  alkenes.  manipulation of  functionalAn i n i t i a l the  ester  of (80) to provide compounds of general structure (85) (W is a  - 85 functionalized  group  derived  from  the  p a r t i c u l a r , we envisaged reduction of the (80)  to  the  a l l y l i c alcohols  ester  compounds  structure (85),  are,  of  course,  i n which W -  Me Sn  moiety  (210)  (Scheme  22).  These  2  w  Me,Sn  H  H  E 80  R  E 85  Me Sn  / — O H  3  R  substances  CH 0R".  2  R  of  In  equivalent to compounds of general  C0 R*  3  (Scheme 22).  (209), which could then, for example, be  converted into ethers of general structure latter  moiety)  CO2R'  209  Me Sn  OR"  3  E  R  210  E  Scheme 22  We were pleased to find that the reduction of the ester function compounds example,  (80) when  to the a l l y l i c alcohols a  solution  stannyl -2 -pentenoate of DIBAL i n hexane, 0°C  for  1.5  h,  (179)  of  methyl  (209) was a f a c i l e process.  i n d i e t h y l ether was treated with a solution  and the solution was s t i r r e d at -78°C for 1 h and at tic  analysis  of an aliquot showed the presence of a  After appropriate workup, the alcohol (211) was  i n a y i e l d of 94%. confirmed  the  For  (Z)-2-(2-propenyl)-3-trimethyl-  single compound, which was subsequently i d e n t i f i e d as the alcohol (equation 35).  of  The  structural  spectral  data  assignment.  obtained  from  (211)  (211)  isolated readily  For example, the i r spectrum of  - 86 -  Me Sn  Me Sn  C0 Me  3  . — OH  3  2  DIBAL,Et 0 2  (35)  -78° — 0°C  21 1  179  (211)  showed a broad absorption at 3348 cm"  stretch  of  nmr  spectrum  of (211)  a  the  0-H  at  S  4.05  (J  =  6  trimethylstannyl  group.  showed the presence of a -CH2OH moiety,  which gave r i s e to a 1-proton t r i p l e t at J 1.2 doublet  to  an alcohol function and an absorption at 769 cm"! a t t r i b u t -  able to the tin-methyl rocking frequency of The  attributable  1  Hz).  (J - 6 Hz) and a 2-proton  Furthermore, high resolution mass  spectrometry showed that the molecular formula was C]^H2 OSn. 2  Under a set of conditions  identical  with  those  described  (Z)-4-methyl-2-(propenyl)-3-trimethylstannyl-2-penten-l-ol  above,  (212)  was  prepared i n 97% y i e l d from the corresponding methyl ester.  212 It was found that the reduction of the (80)  could  also  be  accomplished  However, reaction times were efficient  as  moiety  of  compounds  using l i t h i u m aluminum hydride.  and  the  reactions  were  not  those i n which DIBAL was used as the reducing agent.  example, a s o l u t i o n of (189) room  longer  by  ester  i n d i e t h y l ether was treated  temperature and the mixture was s t i r r e d for 18 h.  with  as For  LAH at  T i c analysis of  the reaction mixture indicated the presence of one major compound (Rf  =  - 87 0.25).  (silica  g e l , development with 5:1 petroleum e t h e r - d i e t h y l  and some polar baseline material. (213)  was  isolated  in  After appropriate workup, the alcohol  65% y i e l d (equation 36).  Me Sn  C0 Et  3  ... / = \  // ^  (36)  /  Bi/ Me SIO 2  1  is a  OH  3  2  (213)  I t may be noted that  Me Sn  2  Bit* Me SIO  ether)  89  213  trans - 2-butene-1.4-diol  hydroxyl groups i s protected.  derivative  in  which  one  of  the  The s p e c t r a l data obtained from (213)  was  found to be In complete agreement with the s t r u c t u r a l assignment. Under a set of reaction conditions s i m i l a r to those LAH  reduction  describing  the  of compound (189), the alcohol (214) was prepared i n 68%  from the corresponding methyl ester.  The spectral  data  obtained  from  (214) was found to be i n complete agreement with the assigned structure.  The  conversion  of  methoxymethyl ether was  the  alcohol  readily  moiety  of  accomplished.  compound (211) Thus,  (Z)-2-(2-propenyl)-3-trimethylstannyl-2-penten-l-ol  a  (211)  solution in  C H 2 C I 2  treated with N,N-diisopropylethylamine and methoxymethyl c h l o r i d e the  solution  was s t i r r e d at room temperature for 3 h.  the reaction mixture indicated the presence of a was  subsequently  identified  as  the  ether  new  (215).  into a  6 4  of was and  Glc analysis of component,  which  After appropriate  - 88 -  workup, the ether (215) was i s o l a t e d i n 79% y i e l d spectral  data  assignment. at  1152  The  obtained  from  readily  cm"  attributable  1  spectrum  of  to  37).  The  confirmed the s t r u c t u r a l  For example, the i r spectrum of (215) showed an  nmr  absorption  the C-O stretch © f an ether function.  (215)  clearly  showed  ±he  presence  of  moiety, which gave r i s e to a 3-proton s i n g l e t at S 3.38,  -CH2OCH2OCH3  2-proton s i n g l e t at S 3.96 4.62.  (215)  (equation  Furthermore,  high  ( « I s n - H *" 4  1  0  Hz) and a 2-proton s i n g l e t at  a a 6  resolution mass spectrometry showed that the  molecular formula was C^3H2502Sn.  Me Sn  —OH  3  Me Sn  211  Compound  (215)  —OMOM  3  215  represents  a  potentially  useful  intermediate.  Conceivably, transmetalation of (215) with an a l k y l l i t h i u m reagent would afford a v i n y l l i t h i u m species (216), which could react with a v a r i e t y of electrophiles  to afford tetrasubstituted alkenes  Alternatively,  these l a t t e r compounds could be formed  by  coupling  v a r i e t y of organic  reaction  of  (215)  with  a  the  (217).  Pd(0)-catalyzed  cross-  electrophiles  (equation 38).  (38) 215  217  216  - 89 However, a l l attempts to effect clean transmetalation of (215) different a l k y l l i t h i u m reagents, failure.  under a v a r i e t y of conditions, met with  For example, a solution of (215)  s i v e l y with methyllithium (ether solution)  i n THF  treated  succes-  After  the  mixture  was  with saturated aqueous ammonium c h l o r i d e , glc and t i c analyses  of the reaction mixture indicated the (215).  was  and HMPA (30 equiv) at - 7 8 ° C ,  and the mixture was s t i r r e d at -78°C for 1 h. quenched  with  presence  of  only  one  compound  Moreover, upon workup, 67% of the l a t t e r material was recovered.  S i m i l a r l y , when the transmetalation reaction was repeated using n-butyllithium or sec-butyllithium i n the absence of HMPA, approximately 65% of (215) was recovered i n each case.  Furthermore, when  the  reaction  was  repeated using sec-butyllithium i n solvent mixtures comprised of THF and HMPA (8:1 to 3:1) the  at - 7 8 ° C , numerous unidentified  vinylstannane  (215)  were  detected  components  (glc  and  tic  including analyses).  Presumably, the s t e r i c a l l y hindered nature of the trimethylstannyl group is  primarily  responsible for the fact that the transmetalation process  i s very sluggish (equation 39)  .^ >^^ a  (39)  S t i l l e and coworkers^ have reported that the Pd(O)-catalyzed crosscoupling  reaction  process.  Since we were not successful  tion  compound  of  of  vinylstannanes  (215)  the  with a l l y l i c halides is a f a c i l e i n effecting  Pd(0)-catalyzed  clean  transmetala-  cross-coupling reaction  - 90 between (215) nately,  and  3-iodo-2-methylpropene  was  investigated.  Unfortu-  a l l attempts to effect coupling between these substances  (equation 40).  failed  For example, when (215) and 3-iodo-2-methylpropene were  (40)  added to a s o l u t i o n of triethylamine-*-*  in  palladium(II)  acetate,  triphenylphosphine  CH3CN and the mixture was s t i r r e d at 85°C for 24 h,  82% of the vinylstannane remained i n solution (glc a n a l y s i s ) . reaction  was  repeated  in  (glc  and t i c analyses).  components  was  isolated  the  were  However, the major component (36% by  glc analysis) was subsequently i d e n t i f i e d as the coupled and  When  CH3CN using bis(dibenzylideneacetone)palla-  dium(O)^ and triphenylphosphine numerous unidentified detected  and  i n approximately 10% y i e l d .  product  (218)  E f f o r t s to increase the  y i e l d by using d i f f e r e n t solvents (THF or DMF) were not successful.  It  should be mentioned that the Pd(0)-catalyzed cross-coupling reaction was also attempted with other vinylstannanes such as (179) vinyl  halides ^ 2  and  vinyl  triflates ^ 2  such  3-methyl-1-trifluoromethanesulfonyloxycyclohexene.  179  as  and  (211)  bromoethylene However,  211  using and these  - 91 latter  reactions  resulted  in  the  formation  of  mixtures containing  numerous u n i d e n t i f i e d components. Although  the  transmetalation  and  Pd(0)-catalyzed  cross-coupling  reactions were not successful with the vinylstannane (215), we f e l t an a l t e r n a t i v e route utilized.  In  for  forming  particular,  tetrasubstituted  alkenes  (equation  41),  since  numerous  the  alcohol  (211)  in  CH2CI2  temperature, t i c analysis of the  was  pale  vinyl  be  iodides  reports i n the l i t e r a t u r e  shown that the process i s smooth and e f f i c i e n t . of  could  we envisaged that vinylstannanes of general  structure (80) could be converted into the corresponding (219)  that  Indeed, when a solution  treated yellow  have  1  with i o d i n e  solution  6 7  at room  indicated  the  presence of one major component along with some polar baseline material. After appropriate workup, the iodide (220) was (equation  42).  The  spectral  s t r u c t u r a l assignment. consisted  of  a  For  3-proton  data  obtained from (220)  example, triplet  isolated  the at  6 1.07  nmr  in  63%  yield  confirmed the  spectrum  of  (220)  (J - 7.5 Hz), a 1-proton  (42) 211  220  - 92 -  t r i p l e t at f 1.64  (J = 6 Hz), a 2-proton quartet at S 2.61  a 2-proton dt at 8 3.09  (J •= 6, 1.5 Hz), a 2-proton doublet at 5 4.24 (J  - 6 Hz), a 1-proton ddt at 6 5.06 at 6 5.08 6 Hz).  (J - 7.5 Hz),  (J - 10, 2, 1.5 Hz),  a  1-proton  (J - 17, 2, 1.5 Hz), and a 1-proton ddt at 8 5.76  (J = 17,  Furthermore, high resolution mass spectrometry showed  molecular  formula  of  compound  (220)  i s CgH^OI.  configuration of compound (220) was assumed to be as  ddt  that  10, the  The stereochemical shown,  since  the  iododestannylation reaction occurs with retention of c o n f i g u r a t i o n . ® 6  Conversion  of  oxymethyl e t h e r , (220)  6 9  the alcohol (220)  into the corresponding methoxyeth-  was r e a d i l y accomplished by treating  a  solution  of  i n CH2CI2 with N,N-diisopropylethylamine and 2-methoxyethoxymethyl  chloride. presence  Glc analysis  of  an  aliquot  of  the  solution  showed  the  of a single compound, which was subsequently i d e n t i f i e d as the  ether (221).  After appropriate workup, the ether (221) was i s o l a t e d  88%  The  yield.  spectral  data  obtained  O  from  (221)  confirmed  in the  O  221  s t r u c t u r a l assignment. depicted  For example,  the  i  H  nmr  spectrum  (which  In F i g . 7) showed the presence of a -CH2OCH2OCH2CH2OCH3 moiety  which gave r i s e to a 3-proton s i n g l e t at S 3.41,  a 2-proton m u l t i p l e t at  4" 3.55-3.61, a 2-proton multiplet at S 3.72-3.77, a 2-proton s i n g l e t 8 4.22 and a 2-proton s i n g l e t at 8 4.75. mass  is  spectrometry  verified  that  the  Furthermore, molecular  high  formula  at  resolution of (221)  is  - 94 -  C  12 21°3 • I  H  By u t i l i z i n g a sequence of steps s i m i l a r to  those  the ether (223) was prepared from the alcohol (212) Me Sn  just  described,  (equation 43).  .— QH  3  The  OMEM  (43) 222  212  spectral  data  \  obtained from compounds (222)  223  and (223) were found to be  i n f u l l accord with the s t r u c t u r a l assignments. The u t i l i t y of compounds (221) and (223) the  as  key  intermediates  synthesis of functionalized, stereochemically defined,  for  tetrasubsti-  tuted alkenes w i l l be discussed i n the following section of this t h e s i s . In the meantime, alternative transformations of the of  compounds  instance, alcohol  of  general  structure  (224)  a p o s s i b i l i t y that we envisaged function  of (223)  will  was  be  the  moiety  discussed.  conversion  of  For the  into an aldehyde moiety, which could then be  treated with a W i t t i g reagent to afford substituted structure (225)  alcohol  (equation 44).  dienes  of  general  Indeed, i t was found that when a solution  (44) R  224  E  R  225  E  of pyridinium chlorochromate, sodium acetate and the CH2CI2  alcohol  (220)  in  was s t i r r e d for 1 h 45 min, t i c analysis of an aliquot indicated  - 95 the presence of only one component (Rf •» 0.77)  ( s i l i c a gel,  development  with 7:3 petroleum ether-ethyl ether), which was subsequently as the aldehyde (226). isolated (226) the  in  82%  After appropriate workup, the aldehyde (226)  y i e l d (equation 45).  spectrum  For example,  showed an absorption at 2859 cm" attributable to the 1  aldehyde carbon-hydrogen stretching frequency and an absorption at cm"  attributable  1  function. singlet  6  1729  to the carbonyl stretching frequency of the aldehyde  Moreover, the at  was  The spectral data obtained from  c l e a r l y showed the presence of an aldehyde function. Ir  identified  9.04.  1  H nmr spectrum  In  addition,  of  (226)  showed  a  1-proton  high resolution mass spectrometry  v e r i f i e d that the molecular formula of (226)  is CgH^OI. H  (45) 220  226  The subsequent conversion of (226) readily  accomplished.  Thus,  when  into the corresponding diene the  aldehyde (226) was added to a  s o l u t i o n of methylenetriphenylphosphorane i n THF and stirred  at  room  temperature  for  2  h,  the  (silica  gel,  development  with  95:5  ether), which was subsequently i d e n t i f i e d as the appropriate  workup,  the  triene  solution  component  petroleum triene  structure.  (Rf  (227).  (227) was i s o l a t e d i n 78% y i e l d .  For example, the "^H nmr of (227)  -  ether-diethyl  s p e c t r a l data of t h i s material was found to be i n f u l l accord assigned  was  t i c analysis of the reaction  mixture indicated the presence of a single UV active 0.66)  was  with  After The the  showed a 3-proton  - 96 -  t r i p l e t at S 1.12 Hz),  a  (J - 7.5 Hz), a 2-proton quartet at 6 2.72  1-proton  doublet at 5 5.16  7.5  6.69  (J  =  17,  (J = 17,  2,  11  Hz).  Furthermore,  By u t i l i z i n g a series of steps up  to  this  synthesized (Scheme  point  23).  Hz),  a  (J = 17, 10, 6 Hz), and a 1-proton dd high  resolution  spectrometry v e r i f i e d that the molecular formula of (227)  discussed  1.5  (J - 11 Hz), a 1-proton doublet at S 5.29 (J  = 17 Hz), a 1-proton ddt at 6 5.76 5  -  2-proton dt at 6 3.15 (J - 6, 1.5 Hz), a 1-proton ddt at 6 5.02  (J - 10, 2, 1.5 Hz), a 1-proton ddt at S 5.04  at  (J  similar  in  The  the  those  thesis,  synthesis  according to the following sequence.  to  of  is  C9H13I.  that  have  the tetraene (230)  was  mass  been  (230) was  accomplished  Reduction of the ester function of  (195) with a s o l u t i o n of DIBAL i n hexane, afforded the  alcohol,  which,  without p u r i f i c a t i o n , was converted d i r e c t l y into the corresponding iodo alcohol (228) afforded  a  (isolated y i e l d -67%). 91%  yield  of  the  Oxidation of this l a t t e r  aldehyde (229) , which was treated with  methylenetriphenylphosphorane to afford, tetraene  (230).  It  should  be  noted  i n 89% y i e l d , the corresponding that  the spectral data of the  compounds shown i n Scheme 23 were found to be i n f u l l assigned showed  structures. a  stretching  broad  For  absorption  example, at  material  3332  accord  with  the  the i r spectrum of compound (228) cm"l  frequency of an alcohol function.  attributable  to  the  0-H  On the other hand, the i r  - 97 -  195  228 PCC.NaOAc, CH CI 2  2  H Ph P=CH 3  2  THF  229  230  Scheme 23  spectrum of (229) carbonyl  Hz).  c l e a r l y showed the  (229)  H  The  high  and  10 15^1> ^11^13^1  C  of  The a  (230) a  n  d  resolution verified  ^11^15l'  vinyl  (J — 11, 0.5 Hz), a 1-proton  mass that  nmr spectrum  conjugated  (J = 17, 0.5 Hz) and a 1-proton dd at S 6.70  Furthermore,  (228),  presence  which gave a 1-proton dd at S 5.18  dd at 6 5.30  spectrometry the  molecular  (J of  -  17,  11  compounds  formulas  are  respectively.  p o s s i b i l i t y of transforming alcohols of general structure  into the corresponding halides (231) (equation 46).  the  1  stretching frequency of an enal function.  of compound (230) moiety,  showed an absorption at 1680 cm" a t t r i b u t a b l e to  (X — halogen) was  I t was f e l t that substances  also  considered  (231), which are p o t e n t i a l l y  s y n t h e t i c a l l y equivalent to the d,a synthons (232), could be useful the development of annulation sequences. ** 3  (224)  for  We were pleased to f i n d that  - 98 -  (46)  the transformation (equation 46) was r e a d i l y accomplished. when a s o l u t i o n of the alcohol (212) phosphine and t r i e t h y l a m i n e tic  analysis  of  (233).  i n CC1 was treated with t r i p h e n y l 4  and the solution was refluxed  for  12  h,  the reaction mixture showed the presence of one major  component (Rf — 0.55) ether-diethyl  70  For example,  (silica  gel,  development  with  95:5  petroleum  ether), which was subsequently i d e n t i f i e d as the chloride  After appropriate workup, the chloride (233) was isolated i n 91%  yield.  Treatment  of a solution of this compound i n  afforded the corresponding iodide (234) (equation  47).  The  spectral  data  in  an  CH2CI2  isolated  of compounds (233)  with iodine  yield  of  95%  and (234) were  (47)  r e a d i l y interpreted and were assigned structures.  4.30,  a 1-proton ddt at 6 5.05  5.10  (J  10,  be  in  full  accord  nmr spectrum of (234)  with  the  showed a  (J - 7 Hz), a 1-proton septet at 6 2.35  Hz), a 2-proton dt at £ 3.15  -  to  For example, the  6-proton doublet at 6 0.95 7  found  (J  -  (J - 6, 1.5 Hz), a 2-proton s i n g l e t at 6 (J = 17, 2, 1.5 Hz), a 1-proton ddt at  2, 1.5 Hz) and a 1-proton ddt at 5 5.77  6  (J — 17, 10, 6  - 99 -  Hz).  Furthermore, high resolution mass spectrometry v e r i f i e d  molecular formula of (234)  is  in  CH2CI2  compounds were formed.  the  CgH^ClI.  It was found that when solutions of a l k y l 2- alkenoates  that  were  treated  2,3-bis(trimethylstannyl)-  with  iodine,  some  For example, a solution of ethyl  (trimethylstannyl)-2-butenoate  (124)  in  CH2CI2  was  unexpected  (Z)-2,3-bistreated  with  a  s o l u t i o n of iodine i n CH2CI2 at -78°C and the purple mixture was s t i r r e d at -78°C for 30 min. indicated  the  T i c and  presence  of  glc  analyses  two  components,  correspond to trimethylstannyl iodide. isolated  of  Me Sn  SnMe  3  (235)  C0 Et  Me  (equation 48).  Me Sn 2  , C H  "  2  ?  8  C I  2  S 2  from  (235)  spectral  data  =  ^  =  (  4  8  )  C0 Et 2  clearly  established the c o n s t i t u t i o n and stereo-  For example, the i r spectrum showed an  absorp-  1  consisted  of  a  ester  function.  ^H nmr  spectrum  2-proton quartet at 6* 4.25 v  a  2  u  e  (235)  6  (J - 7 Hz). l  of  ( J_Sn-H " -* Hz), a 3-proton  (J - 7 Hz), a 3-proton s i n g l e t at 6 2.10  of ^H nmr data to note i s the ~*J_Sri-H methyl  The  a 9-proton s i n g l e t at S 0.32  t r i p l e t at 6 1.32  vinyl  (Z)-2-iodo-  1719 cm" attributable to the carbonyl stretching frequency of  an a,B-unsaturated  and  The  was  235  chemical configuration.  Hz)  )  Me  C  124  at  which  I  3  I  mixture  one of which was found to  The other component,  3  y=^  tion  reaction  i n 91% y i e l d , was subsequently i d e n t i f i e d as ethyl  3- trimethylstannyl-2-butenoate  obtained  the  ( J_Sn-H " 3  4  5  The important piece  Hz) associated  with  the  group, which unequivocally established the regiochemistry  - 100 -  of  the  p r o d u c t t o be as d e p i c t e d by s t r u c t u r e  (235).  The o t h e r  isomer would i n v o l v e a J_s -H which would be much s m a l l e r 4  n  Finally,  high  than  regio45  Hz.  r e s o l u t i o n mass spectrometry v e r i f i e d t h a t the m o l e c u l a r  formula o f (235) i s C H 02lSn2. 9  The  stereochemical  performing a t 5 0.32 while  17  configuration  of  nOe d i f f e r e n c e e x p e r i m e n t s .  (235)  of  enhancement a t 6 2.10 difference  Thus, i r r a d i a t i o n  the  signal  and 8 1.32  experiment  at  6 4.25  (-OCH CH ). 2  confirmed  that  literature  precedent.*"**  spectrum o f  (235), the e f f e c t  the  chemical  f u n c t i o n i n (235)  i s 6*  It  is  the t i n - i o d i n e  93.6,  the  compared  methyl),  of  this  nOe  exchange p r o c e s s  to  note,  vinylic to  iodine  carbon 149.9  6  i n the  in  nmr  atom.  For  a to the  ester  the  starting  (124).  Under  a  s e t o f c o n d i t i o n s s i m i l a r to those d e s c r i b e d above,  (Z)-2-iodo-3-trimethylstannyl-2-pentenoate yield  signal  as one would expect based on  interesting  of  (vinyl  by  (-OCH2CH3) caused s i g n a l  o f the e l e c t r o n e g a t i v e  shift  o f the  The r e s u l t s  3  occurred with retention of stereochemistry,  material  corroborated  (-SnMe.3) caused s i g n a l enhancement a t S 2.10  irradiation  example,  was  from  the  corresponding  (236)  was  prepared  bis(trimethylstannyl)  methyl in  97%  a.^-unsaturated  ester.  C0 Me 2  236  Iododestannylation intensive  mechanistic  reactions studies  ( e q u a t i o n 49) during  the  have been the s u b j e c t past  three  of  decades.71-73  - 101 -  R'—SnR  +  3  l  • R'l  2  +  ISnR  (49)  3  E l e c t r o p h i l i c attack of the halogen molecule on the carbon trialkylstannyl  group  i s the recognized mode of reaction.71-73  been found that different groups on different  rates.  cleavage  methyl  >  reaction  by  iodine  higher can  tin  are  cleaved  by  t  iodine  ^as with  n-butyl) and a fourth group, then the  follows  a l k y l . F o r  the  ease  sequence benzyl > a r y l ~ v i n y l >  mixed  tetra-alkyltin  compounds  the  occur either with retention or inversion of configuration  i n an a l k y l group (R' i n equation 49), depending on the alkyl  j  the  Thus, i f one considers an organotin compound contain-  ing three a l k y l groups (e.g. of  bearing  groups  on  tin  and  of  the  solvent.^  nature  For v i n y l  compounds (R' i n equation 49 is an alkenyl group), the  of  the  trialkyltin  reaction  always  CO  occurs with retention of configuration i n the alkenyl g r o u p . The  mechanism  of  the  iododestannylation  reaction  subject of controversy, largely revolving around the transition  state.  j  i  a  s  depiction  been proposed to account for the  tetra-alkyltin  compounds.  t r a n s i t i o n state (237), which can lead configuration,  still of  In  to  observed  many cases an open Sg2  inversion  or  retention  I  i n methanol).^ •75 2  2  in  C C I 4 ) ,  of  Qn the other hand, i f a  portion of the iodine reagent i s the strongest nucleophile present 2  the  appears to be favoured when the solvent i s the strongest  nucleophile present (e.g.  I  the  0  2  in  is  A charge-transfer mechanism^ or a c y c l i c or an open  S£2 t r a n s i t i o n state^ -75 selectivity  0 0  the reaction apparently involves a  cyclic  S£2  (e.g.  transition  state (238), which always leads to retention of configuration.^2.75 N a s i e l s k i ^ and coworkers have proposed a t r a n s i t i o n state shown i n 0  - 102 -  1.*  \  .Sn • ••solvent  • •  • *  I — I  238  237  (239)  to account for the retention of stereochemistry  iododestannylation  observed  in  the  of v i n y l t r i a l k y l t i n compounds, when the reaction i s  c a r r i e d out i n a polar solvent such  as  methanol.  In  this  case  the  solvent a s s i s t s i n the cleavage of the carbon-tin bond.  / \ / •• a* ' a". SnR,  239 A  possible  transition  stereoselective  literature '75> arises  from  7 7  i  s  3  H  state  that  iododestannylation  stannyl)-2-alkenoates, 7 4  .OCH  of  alkyl  it  for  the  chemo- and  (Z)-2,3-bis(trimethyl-  and that i s i n accord with those reported i n the shown i n (240).  Presumably, the  chemoselectivity  the fact that, of the two v i n y l i c carbons, the carbon a to  the ester function i s more able to bear a since  accounts  can  be  negative  s t a b i l i z e d by the ester function.  the a-carbon becomes more susceptible iodine molecule.  developing  to  charge,  As a consequence,  electrophilic  attack  by  the  Moreover, the cleavage of the carbon-tin bond a to the  ester function i s now f a c i l i t a t e d by the  nucleophilic  iodine molecule i n t e r a c t i n g with the electropositive  portion  t i n atom.  of  the  - 103 -  R C-TTT:C  Me Sn 3  I  SnMe  3  240  Interestingly, though, when an alkyl (£)-2,3-bis(trimethylstannyl)2-alkenoate  was  treated with Iodine, a different type of compound was  formed as compared to that obtained from the corresponding  (Z)  Isomer.  For example, when a solution of methyl (E)-2,3-bis(trimethylstannyl)-2pentenoate  (147) in  C H 2 C I 2  was treated with iodine at room temperature,  and the mixture was stirred for 30 reaction  min,  t i c analysis  the  yellow  mixture did not show the presence of a distinct compound, even  when developing solvents of different polarities glc  of  analysis  of  component with a  the  reaction mixture  retention time  longer  were  showed than  used.  However,  the presence of a new that  of  (147).  This  material was subsequently identified as methyl (E)-3-(iododimethylstannyl)-2-trimethylstannyl-2-pentenoate workup, was isolated in 85% yield  (241),  (equation  50).  and, after appropriate The  spectral  data  (50)  obtained  from  (241)  clearly confirmed the structural assignment.  example, the i r spectrum showed an absorption at 1636 cm"  1  For  attributable  - 104 to  the  carbonyl  function. at  5  Hz), 2.85  stretching  The  nmr spectrum of (241)  ( J.s -H  0.29  frequency  2  =  5  5  H z  n  ) •  a  -  7  Furthermore,  Hz,  3  high  J_Sn-H  resolution  molecular formula of (241) The  ~  an  a,^-unsaturated  ester  consisted of a 9-proton  singlet  6-proton s i n g l e t at 5 0.95  a 3-proton t r i p l e t at S 1.03 (J  of  9  ( J_s -H " 2  (J - 7 Hz), a 2-proton 0  H z  ^  a  mass  n  d  a  3  -P  quartet  of  at  spectrometry  verified  that  the  group  of  (241)  was shown to be B to the  (241)  the  3  J  S  n  .  H  In  2,3-bis(trimethylstanhyl)-2-alkenoate.  iodine.  apparent  upon  substitution  3  of  the  ester  function  of  such  marked  decrease  in  frequency  appears  can  at  1636  stretching  cm'^, while,  by  the  inductive e f f e c t ,  presence  the B-tin  than that of (147).  of  the  Such  This coordination would  iodide  atom of (241) would  atom, since, be  more  due to  be its  electrophilic  The effect of intramolecular coordination at t i n by  oxygen i s also evident In the * C nmr spectra of 3  the  in  be attributed to intramolecular  coordination at t i n by the carbonyl oxygen. facilitated  an  a methyl group on t i n by  compound (147), the corresponding absorption appears at 1685 cm'^. a  s  n  Moreover, i n the i r spectrum of (241), the carbonyl  absorption  alkyl  increase of the J _ s . H i -  This  i n accord with a recent l i t e r a t u r e r e p o r t , ^ which states that is  the  value associated with the v i n y l  methyl group i s 90 Hz, compared to a t y p i c a l value of 55 Hz i n an  increase  6  i s C_]H2302lSn2.  iododimethylstannyl  spectrum  6  s i n g l e t at S 3.84.  r o t o n  ester function on the basis of the following spectral evidence. nmr  6  n  (241).  chemical s h i f t of the carbonyl carbon of (241)  to 6 185.6  for the carbonyl carbon of (147).  (depicted  in  For  example,  i s S 193.6, compared  The type  of  coordination  (241A)) i s i n accordance with l i t e r a t u r e r e p o r t s , ^  9  which  - 105 indicate that intramolecular coordination at  tin  by  oxygen  can  only  occur to any appreciable extent v i a a 5-membered r i n g . The  formation of compound (241)  represents  an example of a complete  reversal i n s e l e c t i v e l y i n the iododestannylation of  a  'mixed'  tetra-  ,0.  241 A  organotin  compound.  That  is,  an a l k y l t i n - c a r b o n bond was cleaved i n  preference to a v i n y l t i n - c a r b o n bond. recently (242). afforded  been  reported®  to  0  the  corresponding  compound  a argued  (243)  in  with  C D C I 3  i n approximately 80% y i e l d  n n . Me M C0 Q  2  2  '"  ^y ^  (51)  ^"C0 t 2 Me  243  that intramolecular assistance at t i n by oxygen, during occur  in  the  transition  (depicted i n (244)), v i a formation of a 5-membered r i n g . t i o n constrains the v i n y l carbon linked to t i n to be In and  results.  !  the approach of iodine to carbon, can  position  iodine  / ^"- * \\ ^^S n B u l  3 3  242  was  (242)  A geometric argument was used to explain these  ,SnBu SnBu  has  occur i n a s t r u c t u r a l l y s i m i l a r compound  Thus, treatment of a solution of  (equation 51).  It  This reversal of s e l e c t i v i t y  state  This coordinathe  equatorial  the carbon of an a l k y l group to be i n an a p i c a l p o s i t i o n .  Thus, the a l k y l group becomes susceptible to e l e c t r o p h i l i c  attack  (see  - 106 -  R —•I — I  #  OMe  244  (244)),  which  results  in  the  preferential cleavage of the alkyl-tin  bond. We feel that the reversal of selectivity stannylation  of  compound  observed  the  iodode-  (241) can also be rationalized by invoking a  geometric argument similar to that discussed above. the  in  As  a  consequence,  process most likely occurs via a transition state analogous to that  depicted in (244). Presumably, the low yields of 60-75% observed for the lation  of compounds of general structure (209) can be rationalized by a  competing oxygen.  pathway Such  a  involving rationale  intramolecular is  borne  out  coordination  R  evidence  209  are  of polar baseline material.  identical  with  t i n by since tic  with  iodine  E  of the reactions, the solutions were yellow. tions  at  experimentally,  analysis of reaction mixtures involving treatment of (209)  showed  iododestanny-  Moreover, upon completion These latter two  observa-  those evident in the iodination of compound  - 107 (147)  (equation 50).  compounds  such  as  This i s i n contrast to the  iododestannylation  of  (124) and (233), i n which the y i e l d s were >90%.  In  these cases, no polar baseline material was evident ( t i c  analysis)  and  the solutions were pale purple upon completion of the reaction.  Me Sn  SnMe,  Me  C0 Et  H  3  2  1 24  With  a f a c i l e synthesis of v i n y l iodides such as (235) and (236)  hand, a b r i e f study was i n i t i a t e d to determine t h e i r synthetic In  particular,  we  ethers  (246).  utility.  envisaged reduction of the ester moiety of (245)  afford the corresponding alcohols, which could then Thus,  it  may  be  noted  that  be  the  converted ethers  at  (246)  to  into are  p o t e n t i a l l y s y n t h e t i c a l l y equivalent to the d,d synthons (247), i n which the  two  donor centres are c i s - r e l a t e d (equation 52).  245  246  centres i n (246) could afford  vinyllithium  be  selectively  species,  which  I f the two donor  247  and  successively  deployed  to  could then react with appropriate  e l e c t r o p h i l e s , a synthesis of stereochemically defined  tetrasubstituted  alkenes would have been r e a l i z e d . We  were  pleased to f i n d that when a solution of (236)  i n ether was  - 108  t r e a t e d w i t h DIBAL a t and  at  0°C  -  - 7 8 ° C and the mixure was s t i r r e d a t  for 1 h,  the a l c o h o l  a p p r o p r i a t e workup ( e q u a t i o n  (248)  53).  It  was i s o l a t e d  should  be  -78°C for 1  i n 85% y i e l d  noted  that  h  after  (248)  is  (53)  thermally unstable, evident.  The s p e c t r a l  accord (248)  with  the  upon g l c  analysis,  (248)  assigned structures.  frequency  of  an  alcohol  at  S 1.16  Hz).  (J = 7,  i r spectrum o f to  the  O-H  The ^H nmr spectrum o f  ( J_sn-H 2  triplet  formula of  Unfortunately,  (248)  =  ^  '  6 1.54  at  H z ) , a 2 - p r o t o n dt a t  3-proton  a  (J = 6 H z ) , a  5 4.26  (J  =  ether  included  2-methoxyethoxymethyl  69  failed.  methoxymethyl  tert-butyldimethylsilyl methylsilyl  Various  the  alcohol  conditions chloride,  chloride, chloride,  that  a  corre-  were i n v e s t i g a t e d .  These  into  N,N-diisopropylethylamine,  CH2CI2,  imidazole,  pyran,  p y r i d i n i u m p.-toluenesulphonate,  silyl  chloride,  sulfide,  (248)  CH2CI2,  N,N-diisopropylethylamine,  trifluoromethanesulfonate,  lithium  6,  i s CgH^702lSn.  attempts to c o n v e r t  sponding  is full  F u r t h e r m o r e , h i g h r e s o l u t i o n mass s p e c t r o m e t r y v e r i f i e d  the m o l e c u l a r  CH2CI2,  1.5  the  attributable  1  function.  (J = 7 H z ) , a 1 - p r o t o n  6 2.23  2 - p r o t o n qt a t  were found to be i n  For example,  showed a 9 - p r o t o n s i n g l e t a t 5 0.90  triplet  extensive decomposition  d a t a d e r i v e d from (248)  showed a b r o a d a b s o r p t i o n a t 3349 cm"  stretching  1.5  since,  2,6-lutidine,  CH2CI2® and 3  CH3CN® . 4  81  64  tert-butyldi-  CH2CI2® , d i h y d r o 2  tert-butyldimethyl-  The o n l y p r o d u c t t h a t  was  - 1 0 9 -  i s o l a t e d i n m o s t c a s e s w a s t h e c o r r e s p o n d n ig a c e t y l e n i c e t h e r . t h e  A  f o r m a o t in o f c o m p o u n d s o f g e n e r a l s t r u c t u r e ( 2 4 6 ) w a s n o t  a d d i t i o n a l w o r k i n t h i s a r e a i s r e q u i r e d .  C . S y n t h e s s i o f f u n c t i o n a l i z e d s t e r e o c h e m c i a y l d e f n ie d t e t r a s u b s t i t u t e d a k le n e s  T h e v i n y l i o d i d e s ( 2 4 9 ) , w h c i h w e r e p r e p a r e d p r e v o iu s  s e c t i o n , r e p r e s e n t  a s  d e s c r b ie d  p o t e n t i a l l yu s e f u l n it e r m e d a it e s  p r e s u m a b y l , t r e a t m e n t o f s u c h c o m p o u n d s  w t i h  a n  s i n c e  a l k y l i t h i u m  r e  s h o u d l r e s u l t i n t h e f o r m a o t i n o f t h e c o r r e s p o n d n ig v i n y l i t h i u m s p ( 2 5 0 ) .C o n c e v ia b y l t h e s e l a t t e r s p e c i e s , u p o n t r e a t m e n t w t i h a t e  e l e c t r o p h i l e s , s h o u d l  a k le n e s ( 2 5 1 ) u i m  a f f o r d t h e c o r r e s p o n d n ig f u l l y s u b s t i t u t e d  ( e q u a t o in 5 4 ) .  s p e c i e s( 2 5 0 )  a p p r o  w o u d l  T h u s , i t m a y b e n o t e d t h a t t h e t h e n  b e  s y n t h e t i c a l ye q u v ia e l n tt o  v  t  d s y n t h o n r e p r e s e n t e d b y s t r u c t u r e ( 2 5 2 ) .  (54)  252 T h e  p r o c e s s  o f l i t h i u m i o d i n ee x c h a n g e '  l i t h i u m t i ne x c h a n g e  ( t r a n s m e t a a lt o in  i s a n a o l g o u s  t o  t h e  p r o c e s s ) w h c i h w a s d s i c u s s e d  - 110 the general introduction. leading  For instance,  the  reaction  is  reversible,  to an equilibrium mixture favouring the more stable organolith-  ium species.  Moreover, the lithium-iodine exchange has been assumed  proceed through a four-centred t r a n s i t i o n state  R  LI  I  R  (253).  to  7b  253  It  was  conditions  thus under  generated.  After  our which some  intention the  to  vinyllithium  experimentation  found that conditions that cleanly species  species  (250)  could  be  with the iodide (221), i t was  produced  the  corresponding  lithio  involved treatment of a THF solution of (221) with 2.2 equiv of  n-butyllithium at -78°C for quenched  with  15  min.  (254)  When  the  latter  solution  was  saturated aqueous ammonium c h l o r i d e , glc analysis of the  solution showed the presence of a 1:1 diene  find the appropriate experimental  and  mixture  the hydrocarbon n-octane  of  two  compounds,  (equation 55).  the  On the other  (55)  hand, when the  reaction  was  repeated  employing  only  1.1  equiv  of  n - b u t y l l i t h i u m , glc analysis of the quenched (saturated aqueous ammonium chloride) s o l u t i o n showed the presence of a  9:1  mixture  of  two  com-  - Ill -  pounds,  the  dienes  consequence, reaction  (254)  and (255), respectively  i n order to avoid the presence of  mixture,  most  (equation 56).  n-butyl  iodide  As a  in  the  of our experiments were done with 2.2 equiv of  n-butyllithium.  Direct a l k y l a t i o n of the v i n y l l i t h i u m reagents derived from lithiumiodine  exchange  fashion to alkenes  of  afford  (entries  the the  1-6,  vinyl  iodides  stereochemically  (249),  proceeded i n a smooth  homogeneous  tetrasubstituted  Table X) as the sole substitution products.  For  example, a s o l u t i o n of the v i n y l l i t h i u m reagent i n THF, derived from the vinyl  iodide (221), was treated with l-bromo-3-methyl-2-butene at -78°C  and the mixture was s t i r r e d at -78°C for 30 min. been  quenched  with  saturated  After the mixture  aqueous ammonium c h l o r i d e , t i c  indicated the presence of one major component (Rf — 0.33) development  with  4:1  petroleum  ether-diethyl  material was i s o l a t e d i n 67% y i e l d and was  ether).  subsequently  analysis  (silica The  had  gel, latter  identified  as  (Z)-  5-ethyl-4-(2-methoxyethoxy)methoxymethyl-8-methyl-1,4,7-nonatriene  (256)  (equation 57).  the  ^H nmr  data.  CH2OMEM, a l l y l , at  The structure of (256) was v e r i f i e d by analysis of For example, i n addition to the signals due to the  and ethyl groups, there appeared two  5 1.67 and S 1.69,  3-proton  a broad 2-proton doublet at J 2.83  singlets  (J = 7 Hz) and  - 112 -  T a b l e X:  P r e p a r a t i o n o f v i n y l l i t h i u m s p e c i e s and t h e i r r e a c t i o n s electrophiles  W  LI  W  E'  Jtt-BuLl THF  W  249  Entry'  with  251  W  249  E'X  251  C  Yield (%)  221  Et  CH OMEM  a  221  Et  CH OMEM  d  221  Et  221  Et  227  Et  230  257  93  Me C-CHCH Br  256  67  CHoOMEM"  n-BuI  255  65  CH OMEM  C1(CH ) I  258  72  n-BuI  259  54  260  67  2  2  2  d  2  CH=CH  CH =CHCH CH 2  2  2  2  CH=CH  Mel  c  2  2  2  5  CH =CH(CH ) I 2  2  3  Reaction conditions: A s o l u t i o n (THF, -78°C) o f (249) was t r e a t e d w i t h n - B u L i (1.1 o r 2.2 e q u i v ) , t h e r e a c t i o n m i x t u r e was s t i r r e d a t -78°C (10-15 min), t h e a l k y l a t i n g agent E'X was added, t h e r e a c t i o n m i x t u r e was s t i r r e d a t -78°C (10 min-2 h) and quenched (NH4CI-H2O) or warmed t o 25°C (30 min-7 h) and quenched ( N H ^ C l - ^ O ) . These m a t e r i a l s were p a s s e d through a column o f a c t i v i t y I b a s i c alumina immediately p r i o r t o use, except f o r l-bromo-3-methyl-2butene ( e n t r y 2 ) , which was d i s t i l l e d immediately p r i o r t o u s e . c  Yield of purified, d i s t i l l e d  d  MEM = CH OCH CH OMe. 2  2  2  product.  - 113 -  (57)  a  one  proton  multiplet  i n the region 5 4.95-5.05.  r e s o l u t i o n mass spectrometry v e r i f i e d (256)  is  that  molecular  1 7  2  of  3  when  a  solution  of  the  derived from the v i n y l iodide (221), was  v i n y l l i t h i u m reagent i n THF, treated  with  iodomethane  and the mixture was s t i r r e d at -78°C for 10 min, the alkene  (entry 1, Table X) was isolated i n 93% y i e l d after The  formula  C H 90 .  Similarly,  -78°C  the  Furthermore, high  spectral  data  at  (257)  appropriate workup.  obtained from (257) were found to be i n f u l l accord  with the assigned structure. When less reactive halides such as 5-chloro-l-iodopentane were warmed to  room  (entry  4)  n-butyl  iodide  (entry  3)  and  were employed, the reaction mixtures  temperature  to  ensure  reaction.  The  alkenes formed from the experiments summarized i n entries 3 and 4,  (255)  and (258), were i s o l a t e d i n y i e l d s of 65% and spectral  data  complete  72%,  respectively.  The  of the l a t t e r two compounds are f u l l y i n accord with the  assigned structures (Table X ) .  The ^H nmr spectrum of (258)  i s depicted  i n F i g . 8. The  formation  of  tetrasubstituted  iodides (249), i n which W - CH=CH , 2  process.  For  example,  was  alkenes from the corresponding also  found  to  be  a  facile  treatment of a solution of the triene (227)  THF with 1.1 equiv of n-butyllithium at - 7 8 ° C , followed by  addition  in of  - 115 n-butyl  iodide and warming of the reaction mixture to room temperature,  afforded the triene (259) The  spectral  data  i n an isolated y i e l d  derived  of  2.Q-Bul,-78°  (J - 7  Hz),  a  4-proton  1-proton  is  C  1 3  H  Similarly,  dd  2 2  at  6  6.73  (J  =  that  the  in  the  (J - 7 Hz), a 1-proton  17, 10 Hz).  (J - 17, 1.5  Hz)  Furthermore, high  molecular  formula  of  the pentaene (260) was obtained from the iodide (230) by corresponding  vinyllithium  reagent  with  5-iodo-l-  In t h i s reaction, glc analysis of the crude product showed the  presence of 10%'of the corresponding product distillation  (261).  since,  However,  of the crude o i l afforded the pentaene (260)  I t should be noted that this l a t t e r compound i s ing,  (259)  .  a l k y l a t i o n of the pentene.  multiplet  (J - 10, 1.5 Hz), a 1-proton dd at 5 5.14  r e s o l u t i o n mass spectrometry v e r i f i e d (259)  a  S 1.26-1.44, a 2-proton t r i p l e t at S 2.19  dd at 6 4.98 and  the •'•H nmr spectrum of  i n addition to the signals due to the ethyl and a l l y l groups, a  3-proton t r i p l e t at 6 0.92 region  For example,  (58)  /  —25°C 259  with the assigned structure.  58).  Bu  227  showed,  (equation  from (259) were found to be i n f u l l accord  1.n-BuLi(1.1eq),THF //  54%  careful  i n 67% y i e l d .  structurally  interest-  as one moves around the central double bond i n a clockwise  fashion beginning at the v i n y l group, each successive group possesses an additional  carbon  atom.  As expected, the ^H nmr spectrum of (260)  very complex and consists of multiplets corresponding to  the  is  methylene  - 116 -  protons  and  vinylic  protons.  Nevertheless,  the spectral data derived  from (260) were found to be i n f u l l accord with the assigned Interestingly, (262),  derived  when a  THF solution  the  vinyllithium  species  by treatment of the corresponding iodide (221) with 2.2  equiv of n - b u t y l l i t h i u m , was treated iodide  of  structure.  with  3-iodo-2-methylpropene,  the  (221) was returned (93%) v i a a "reverse" lithium-iodine exchange  (equation 59).  Presumably, the greater s t a b i l i t y  of  the  allyllithium  (59) 262  species,  compared  equilibrium to the However,  complex  at  to that of the v i n y l l i t h i u m species (262) right,  thus  returning  the  at  with -48°C  1 to  equiv afford  of  cuprous(I)  iodide  (221).  bromide•dimethyl  sulfide  the corresponding vinylcopper(I)  species  When t h i s l a t t e r reagent was treated with  -48°C  3-iodo-2-methylpropene  and the mixture was s t i r r e d at -48°C for 45 min, glc  of the solution indicated the presence of a minor product  vinyl  drives the  t h i s problem was r e a d i l y overcome by treating the v i n y l l i t h i u m  species (262)  (263).  221  (254)  and  a  amount  (7%)  analysis of  the  major amount (86%) of the coupled product (266).  - 117 Column chromatography of the crude o i l on s i l i c a gel afforded the alkene (266)  i n an i s o l a t e d y i e l d of (69%)  (equation 60).  The spectra derived  from (266) were found to be i n f u l l accord with the assigned  structure.  i  (60)  263  For  example,  the  266  nmr spectrum of (266)  showed, i n addition to the  signals due to the CH2OMEM, e t h y l , and a l l y l groups, a 3-proton at S 1.69,  a 2-proton singlet at 5 2.85,  a 1-proton doublet at 6 4.64 (J  - 0.5 Hz) and a 1-proton doublet at 6 4.75 high  resolution  (266)  is  C  1 6  H  2 8  (entries The  tively.  Furthermore,  3  species  reactions  (263)  efficient  were  coupling  and 3-iodo-2-methylpropene,  quite  It should be  efficient  even  between  noted  with  (264)  that  substrate  (223) group.  and (265)  i n isolated yields  of  77%  and  70%,  respec-  introduction of a functionalized  e l e c t r o p h i l e (2,3-dibromopropene) summarized by entries 2, 4 and 5. each  of  sole  substitution  compounds  the  summarized i n entries 1 and 2 afforded the corresponding  Also of note i s the e f f i c i e n t  the  the  the reactions  1 and 2, Table XI) containing a f a i r l y bulky iso-propvl  reactions  alkenes,  Hz).  0 .  summarized i n Table XI were c a r r i e d out. coupling  (J ~ 0.5  mass spectrometry showed that the molecular formula of  As a consequence of the clean and vinylcopper(I)  singlet  In  reactions (Table XI) the alkene (251) was i s o l a t e d as the product.  The  spectral  data  derived  were i n f u l l accord with the assigned structures.  from  these  The ^H nmr  - 118 Table X I :  Preparation of vinylcopper(I) species and t h e i r reactions with electrophiles  W /  /  3  W  2  E'  W  2  _  249  Entry  Me S.Cui  1.n-BuLI. CuBr.Me S  249  R  251  E'X  W  251  b  Yield (%)  c  223  i-Pr  CH OMEM  CH =C(Me)CH I  264  77  223  i-Pr  CH OMEM  CH =C(Br)CH Br  265  70  221  Et  CH 0MEM  CH =C(Me)CH I  266  69  221  Et  CH 0MEM  CH =C(Br)CH Br  267  78  227  Et  CH=CH  CH =C(Br)CH Br  268  74  c  2  2  c  2  2  c  2  c  2  2  2  2  2  2  2  2  2  2  Reaction conditions: A solution (THF, -78°C) of (249) was treated with n-BuLi (2.2 equiv), the reaction mixture was s t i r r e d at -78°C (10-15 min), CuBr.Me S (1 equiv) was added, the mixture was s t i r r e d at -48°C (20-30 min), E'X was added, the mixture was s t i r r e d at -48°C (45-60 min) and then quenched (NH4C1-H 0) or warmed to 25°C (30 min-7 h) and quenched ( N H 4 C I - H 2 O ) . 2  2  These materials were passed through a column alumina immediately p r i o r to use Y i e l d of p u r i f i e d , d i s t i l l e d product. MEM = CH 0CH CH 0Me. 2  2  2  of  activity  I  basic  - 119 spectrum of compound (268) It (260) 5,  is  (entry 4) i s depicted i n F i g . 9.  apparent from the e f f i c i e n t  formation of compounds (259) and  (entries 5 and 6, respectively, Table X) and compound (268)  Table  (entry  X I ) , that the metal-coordinating OCH OCH CH OMe function 2  structure (269), effecting  in  which  conversions  of  M=Li the  or type  2  Cu-SMe )  is  2  shown  in  2  not  necessary  equation  (see for  61 ( i n which  W = CH 0MEM). 2  I,  E'  W  W  269  Based on w o r k ' " ' laboratory,  we  03  that had  been  carried  out  previously  in  our  envisaged that, perhaps, suitable reagents derived from  the v i n y l iodides (249) could be conjugatively added to enones.  We were  thus pleased to f i n d that after successive addition of magnesium bromide etherate (1.1 equiv), cuprous(I) bromide•dimethyl sulfide complex eq), 2-cyclohexen-l-one equiv)  8 6  to a  THF:Et 0 2  (1.05 equiv) and boron t r i f l u o r i d e etherate (1:2).  solution  (-78°C)  of  the  (0.23 (1.1  vinyllithium  reagent (262), followed by s t i r r i n g of the reaction mixture at -78°C for 3 h, the substituted cyclohexanone (270) was i s o l a t e d i n a y i e l d of (equation  62).  68%  The spectral data derived from (270) was found to be i n  F i g . 9:  The 400 MHz H nmr spectrum of (268) A  - 121 -  (62)  f u l l accord with the assigned structure. showed  spectrum  1  showed,  function.  The  nmr  spectrum  of  i n addition to the signals due to the CH2OMEM, a l l y l ,  groups, a 3-proton multiplet i n multiplet  the  1-proton  region  multiplet  in  the  in  region  C  H 1 8  the 5  r e s o l u t i o n mass spectrometry v e r i f i e d is  6  1.64-1.78,  (270)  and ethyl  a  1-proton  i n the region S 2.07-2.17, a 2-proton multiplet i n the region  S 2.22-2.32, a 2-proton multiplet  It  ir  an absorption at 1714 cm" attributable to the carbonyl stretch-  ing frequency of a ketone  (270)  For example, the  region  5  3.04-3.12. that  the  2.35-2.44  and  Furthermore,  molecular  a  high  formula  of  30°4-  should be noted that the y i e l d of (270) was lower (approximately  40%) when the reaction was performed on a large scale (up to 0.8  mmol),  compared to the scale of the reaction discussed above (0.2 mmol). When  the  vinyllithium  reagent derived from the transmetalation of  (223) was treated with the reagents described above, the corresponding 63).  conjugate  addition  yield  of  the  product (271) was only 31% (equation  Presumably the s t e r i c bulk of the iso-propyl  group  is  primarily  responsible for the fact that the conjugate addition i s very sluggish. In  summary,  it  i s worthwhile to note that i n the  tetrasubstituted  alkenes prepared v i a the two methods discussed previously, substituents  on  the  double  bond  (R  two  (trans)  and W) are derived from r e a d i l y  - 122 -  O OMEM (63)  271  synthesized substituents 24).  The  a,8-acetylenic (E  esters,  while  the  other  two  and E') are introduced by a l k y l a t i o n reactions  demonstrated  and  potential  feasibility  of  (trans) (Scheme  synthetically  manipulating the ester function, along with the p o s s i b i l i t y of employing a wide v a r i e t y of functionalized a l k y l a t i n g agents i n addition to listed  in  Tables  X  and  IX, indicates that a v e r s a t i l e and e f f e c t i v e  synthesis of functionalized, stereochemically alkenes has been d e v e l o p e d .  those  defined  tetrasubstituted  87  derived from C0 R' function  derived from second alkylation reaction  2  R from the parent acetylene R—==—C0 R  E derived from transmetalationalkylatlon reaction  2  Scheme 24  - 123 IV.  Synthesis and chemistry of a l k y l ( E ) - 2 - ( t r i - n - b u t y l s t a n n y l ) - 3 - t r i methylgermyl-2-alkenoates  and a l k y l (Z)-3-(tri-n-butylstannyl)-2-  trimethylgermyl-2-alkenoates.  A.  Synthesis of the t i t l e compounds  The  Pd(0)-catalyzed  addition  esters has been shown to be a stereoselective alkenoates.  formation  of hexamethylditin to a a c e t y l e n i c  smooth  and e f f i c i e n t  4 5  reagents  to 1-alkynes  demonstrated  addition  afforded  the  of  Me Sn  SiR'  - H 3  3  3  R  81 The adducts  4  3  272  trialkyl-  64).  4 5 , 4 6  3  (64)  H  (272) were i s o l a t e d i n y i e l d s ranging from 65% (R - i - P r , R'  - __t-BuMe ) to 92% (R - THPOCH CH , R' - n - B u ) . 2  decided  For  corresponding  (272) i n a regio- and stereoselective manner (equation  R' SiSnMe Pd(PPh )  we  4 6  'mixed' b i m e t a l l i c reagents to 1-alkynes.  example, i t was found that the Pd(0)-catalyzed silyltrimethyltin  f o r the  of a l k y l (Z)-2,3-bis(trimethylstannyl)-2-  Recently, two reports i n the l i t e r a t u r e '  the f e a s i b i l i t y of adding  adducts  process  2  46b  2  As a  consequence,  to investigate the p o s s i b i l i t y of the Pd(0)-catalyzed addi-  t i o n o f trialkylstannyltrimethylgermanium compounds  to  a,B-acetylenic  esters, and to determine the regiochemical outcome of such a reaction. In  the f i r s t  such study we decided to u t i l i z e trimethylgermyltri-  methyltin, since t h i s compound was conveniently prepared i n 76% y i e l d by  - 124 the  addition  of trimethylgermanium bromide to a solution of trimethyl-  stannyllithium i n THF at - 2 0 ° C . performed.  To  a  solution  As such, the following  of ethyl 2-butynoate  experiment  (70)  was  i n THF was added  trimethylgermyltrimethyltin (1 equiv) and (PPl^^Pd (0.02 equiv) and the mixture  was  stirred  at  50-55°C  development with 9:1 petroleum  for 30 h.  T i c analysis ( s i l i c a g e l ,  ether-diethyl  ether)  of  the  reaction  mixture indicated the presence of only one component (Rf = 0.40) absence of components corresponding to ever,  glc  analysis  of  an  aliquot  the  starting  materials.  solvent,  followed  by  column  chromatography  s i l i c a gel afforded a clear colorless o i l . oil  showed, amongst other signals,  and 8 1.96,  each  Integration  of  of  which  these  to  a  to  these  signals  vinyl  methyl  were  The  subsequently  methylgermyl-2-trimethylstannyl-2-butenoate  compounds  identified  (124), ethyl  methylgermyl)-3-trimethylstannyl-2-butenoate  (274),  Me  C0 Et 2  273  as  correethyl  respectively. and (274) was  SnMe  3  COjEt  group.  (273) and ethyl ( Z ) - 3 - t r i -  Me Ge  124  8 2.03  (Z)-2,3-bis(tri-  for the structures of compounds (124), (273)  Me  this  showed that these signals had r e l a t i v e  (Z)-2,3-bis(trimethylstannyl)-2-butenoate  Evidence  of  of the brown o i l on  3 d i s t i n c t signals at 5 2.07,  areas of approximately 1:1.3:2.0, respectively. sponding  Removal  The ^H nmr spectrum of  corresponded  singlets  How-  indicated the presence of 3 major  components i n a r e l a t i v e proportion of approximately 2:1:1. the  and the  3  Me  CO Et z  274  - 125 obtained as follows.  When a mixture of these  3  was heated at 1 1 0 ° - 1 1 5 ° C for 10 h, t i c analysis with 9:1 petroleum ether-diethyl ether) major  components (Rf — 0.62,  0.51,  inseparable ( s i l i c a gel,  indicated  0.40).  the  (77), and  identified  ethyl  as  ethyl  3  H  Me  C0 Et 2  SnMe  H  Me Sn  GeMe  Me  C0 Et  3  3  3  3  H  Me Ge  C0 Et  Me  SnMe  3  2  273  inseparable  component  was  butenoate  (124).  identified  2  3  275  Identical  As a  compounds ((124), as  ethyl  consequence,  of  (273), (274)), the minor  (Z)-2,3-bis(trimethyl-stannyl)-2-  This assignment was made on the basis of the chemical  s h i f t of the v i n y l  methyl  group  (6  2.07),  which  was  found  to  be  with that of the v i n y l methyl group of an authentic sample of  The structures of compounds (273) of  the  spectra of (273) 1  (275).  were found to be i d e n t i c a l with those of an authentic sample of  initial  cm" ,  (273)  since the corresponding  ethyl (E)-2,3-bis(trimethylstannyl)-2-butenoate.  analysis  subse-  (E)-2,3-bis(trimethylstannyl)-2-butenoate  77  (124).  were  (E)-3-trimethylgermyl-2-trimethylstannyl-2-butenoate  Me Sn  3  Column chromatography of the  The former compound (77) was r e a d i l y i d e n t i f i e d ,  the  of  (Z)-2-trimethylgermyl-3-trimethylstannyl-2-butenoate  ethyl  spectra  development  presence  crude o i l on s i l i c a gel r e a d i l y afforded three o i l s , which quently  compounds  corresponding and (275)  respectively,  and  spectral  (275)  data.  showed absorptions  were For  at  1709  verified  by  example, the i r cm"  1  and  1704  attributable to the carbonyl stretching frequency of  the a,/8-unsaturated ester functions. showed a 9-proton s i n g l e t at 6 0.23  The ( J_Sri-H ** ^ 2  nmr 5  H z  ^'  spectrum a  of  (273)  9-proton singlet  - 126 at S 0.31  (-GeMe ). a 3-proton t r i p l e t at 6 1.27  singlet  at 6 2.03  ( J.Sn-H ~ 3  4  8  Hz  )>  a  n  d  On the other hand, the ^H nmr  9-proton  singlet  0.26  ( Js -H " 2  5  tin  4  1  1  H z  )  a  n  d  a  showed  v  f  (1=7  Hz),  a  3-proton  l  l  u  e  s  f°  r  (J -  coupling between the  l  u  e  and (275) was readily assigned.  For  instance,  the  of 48 Hz (vinyl methyl of (273)) shows that the trimethyl-  stannyl group must be B to the ester as depicted i n structure (273). the  other hand, the J_s -H 4  v  n  a  l  u  °^ ^  e  depicted i n structure (275)  On  Hz ( i - y l methyl of (275)) shows v  that the trimethylstannyl group must be  The  a  and the protons of the v i n y l methyl group, the regiochemistry  compounds (273) v  (275)  2-proton quartet at 5 4.10  a  Hence, on the basis of the J_sri-H  atom  Jsn-H  ( J.Sn-H "  of  (J  Hz), a 9-proton singlet at 5  4  n  3  7 Hz).  3  S  spectrum  (-GeMe ). a 3-proton t r i p l e t at 6 1.27  s i n g l e t at 6 2.00  of  at  3-proton  2-proton quartet at 6 4.18  a  - 7 Hz).  0.27  (J - 7 Hz), a  3  a  n  to  the  ester  function  as  (or (274)).  stereochemical assignments related to compounds (273), (274) and  (275) were made for the following reasons. addition  The i n i t i a l  Pd(0)-catalyzed  of trimethylgermyltrimethyltin to ethyl 2-butynoate,  under the  mild reaction conditions described previously, can be assumed to lead to the  formation  of  cis-adducts only ( i . e .  the subsequent thermolysis reaction, (124) had  -+  (77) and (274) -» (275).  two  group  reaction.  of  (274)  (5  1.96)  of  the  adducts  During  isomerized,  That the l a t t e r isomerization process  occurred was shown by the fact that the  methyl  (124), (273), (274)).  signal  disappeared  due  to  during the  the  vinyl  thermolysis  Moreover, the crude thermolysis product mixture showed a  new  s i n g l e t at 6 2.00 which was assigned to the v i n y l methyl group of (275), the geometric isomer of (274).  On the other hand, the signal at S 2.03,  - 127 corresponding  to  the  v i n y l methyl group of (273), was also present In  the crude thermolysis reaction mixture.  Hence,  compound  (Z)-2-trimethylgermyl-3-trimethylstannyl-2-butenoate, isomerization. of  compounds  (273),  had not undergone  Conclusive evidence for the stereochemical such  as  (273)  ethyl  configuration  and (275) w i l l be presented l a t e r i n this  section of the t h e s i s . I n i t i a l l y , the o r i g i n addition  of  puzzling.  of  3  equilibrate  3  in  Presumably,  disproportionation  solvent.®  which  the  5 0 - 5 5 ° C ,  that  refluxing with t r i -  Me SnSnMe 3  groups  trimethylgermyltrimethyltin reaction  8  Indeed,  when  the  the  (65)  3  attached  to  as  of  about  undergoes  shown i n equation 6 5 . at  room  It has  temperature  in  Pd(O)-catalyzed addition of (70) was  carried  a  a  tri-  out  in  ^H nmr spectrum of the o i l obtained after workup  showed the presence of compounds (77) proportion  found  hexamethylditin and  +  3  alkyl  methylgermyltrimethyltin to ethyl 2-butynoate at  with  Me SiSiMe  1 3  been shown that such a reaction does occur  DMF  was  (70) was  t i n are larger than methyl, the disproportionation reaction  inhibited.  polar  to ethyl 2-butynoate  However, i t has also been s h o w n , t h a t  alkylsilyltrialkylstannanes or  will  Pd(0)-catalyzed  i n a reaction catalyzed by (PPl^^Pd under  65).  (equation  similar  the  4 6  Me SiSnMe  is  in  However, upon probing the l i t e r a t u r e , ^ i t  hexamethyldisilane  silicon  (124)  trimethylgermyltrimethyltin  trimethylsilyltrimethyltin  THF  compound  28:1:2,  (273)  respectively.  and  (274)  in  a  relative  It was subsequently  that when the reaction was performed i n the absence of solvent,  found  the -^H  - 128 nmr  spectrum  of the product mixture showed the presence of a 1:2.8:8.4  mixture of (77), of  (273)  (neat).  to  (273) (274)  and (274). had  It may thus be noted that  increased from approximately 1:1  As a consequence, a l l subsequent reactions  were  the  ratio  (THF) to  1:3  performed  in  the absence of solvent. In  order  to  avoid  the  presence of hexamethylditin i n the Pd(0)-  catalyzed addition reactions we decided to employ t r i - n - b u t y l s t a n n y l t r i methylgermane.  This  reagent was prepared i n 89% y i e l d by the reaction  of t r i - n - b u t y l t i n hydride with IDA i n THF  at  -20°C,  addition of trimethylgermanium bromide (equation  Bu SnH  1.LDA.THF 2.Me GeBr  3  With  a  3  addition  of  (276)  ethyl 2-butynoate  to  (70),  probe  (66)  3  at hand, the following  the  utility  of  a,^-acetylenic esters. (276)  (1.03  equiv) and  was s t i r r e d at 85°C for 24 h, t i c analysis  the  experiment  Pd(0)-catalyzed  Thus, when a mixture of (PPt^^Pd  ( s i l i c a gel,  (0.03  (Rf  - 0.38,  0.53,  0.90).  on s i l i c a gel afforded 3 o i l s , pressure  (vacuum  3  compo-  Column chromatography of the black o i l  each of which was  pump, 0.1 Torr,  equiv)  development with  95:5 petroleum ether-diethyl ether) indicated the presence of nents  the  276  f a c i l e synthesis of (276)  was conducted i n order to  by  66).  Bu SnGeMe  3 3  followed  1 h).  subjected  to  reduced  Of the 3 substances, the least  polar compound (Rf - 0.90)  was found to  recovered  Of the remaining two compounds, the major one  in  22% y i e l d .  (61% i s o l a t e d y i e l d ) was subsequently  correspond  to  i d e n t i f i e d as ethyl  butylstannyl) -3-trimethylgermyl-2-butenoate  (279)  (276)  and  was  (E)-2-(tri-n-  and the minor compound  - 129 (19% i s o l a t e d y i e l d ) was i d e n t i f i e d as methylgermyl-2-butenoate compounds was spectral  readily  data.  (280).  Me Ge 3  H  Me  The  determined  For instance,  ethyl  by  (Z)-3-(tri-n-butyl-2-tri-  constitution analysis  of  C0 Et  Bu Sn  SnBu  Me  2  The  frequency  nmr spectrum of (279)  9-proton  triplet  at  6  respectively,  3  CO Et z  attributable  the  ( J_Sn-H "* 4  other  multiplet  at  1  0  hand,  s i n g l e t at 5 0.30,  showed a 9-proton  0.87  (J  -  7  singlet  at  S  the  0.24,  a  Hz), a 6-proton multiplet at 6 (J - 7 Hz), a 6-proton multiplet  5  H z  ^  a  n  d  the  a  2  _  P  r  o  t  ^H nmr  o  n  quartet at S 4.08  spectrum of (280)  a 9-proton t r i p l e t at S 0.90 0.92-1.00,  (J = 7  (J - 7 Hz),  a 3-proton t r i p l e t at S 1.29  3-proton s i n g l e t at 6 2.01  S 4.17. coupling  I t should be  ( J_Sn-H ~ ^ 3  noted  constants (J_Sn-H^  ments i n compounds (279)  a  that r  e  *  n  the a  and (280).  c  c  o  r  (  a  6-proton  (J = 7 Hz), a  magnitudes  of  the  tin-proton  i with the regiochemical assign-  For instance,  a 4  function.  1.40-1.57,  ^z) and a 2-proton quartet at  value  ( v i n y l methyl group of (279)) i s i n accord with a J_Sn-H' be a t t r i b u t e d to compound (279)  Hz).  showed a 9-proton  6-proton multiplet at 6 1.23-1.40, a 6-proton multiplet at 6 a  to  6 1.20-1.39, a 6-proton multiplet at 6 1.40-1.58, a 3-proton s i n g l e t  at S 1.95 On  GeMe  showed  of the a,^-unsaturated ester functions.  0.92-1.02, a 3-proton t r i p l e t at 6 1.27 at  and (280)  280  absorptions at 1704 and 1709 cm"l, stretching  latter  corresponding  H  3  3  these  the  the i r spectra of (279)  279  carbonyl  of  w b  of  -i h c  c  10 a  i n which the t i n atom i s a to the  n  o n  Hz ly  ester  In addition to the above spectral data, high resolution mass  - 130 spectrometry v e r i f i e d that the molecular formula of both c  21 44°2 H  It  G e S n  compounds  was  -  should  be  noted that i n the addition reaction discussed above,  22% of the reagent (276)  (n-Bu SnGeMe3) was recovered after  workup.  made to "force" the reaction to completion, but  Efforts  were  these were not successful. in  a  lower  addition  products  returned.  For example, longer reaction times  y i e l d of the addition products (279)  when an excess of (276)  (- 5 equiv) was  remained  utilized,  unchanged,  and  and (280). the  led  used  phosphine  outcome  included  of  the reaction.  (276)  Finally,  to ethyl 2-butynoate  investigated  using  a  of  progress  or  Other Pd(0) sources  on that  tri-n-butylstannyltrimethyl-  (70) proceeded i n a reasonable y i e l d  and (280), the generality of variety  this  and (278)  shown i n  XII were prepared i n isolated y i e l d s of 48-61% and 14-19%, In each case (Table XII) the reactions were performed neat 8 5 - 1 0 0 ° C for 5-24 h. C  the  black  oils  As  Table  respectively. at  tempera-  The reactions were e a s i l y monitored by  t i c analyses and the products were r e a d i l y separated by of  reaction  of a,B-acetylenic esters (90).  such, the compounds of general structure (277)  tography  changing  6 6  to afford the adducts (279)  of  was  bis(dibenzylideneacetone)palladium(0)/triphenyl-  Since the Pd(0)-catalyzed addition  tures  the  and bis(triphenylphosphine)palladium(II)chloride/diisobutyl-  66  aluminum h y d r i d e .  was  of  over 4 equiv of (276)  to a lower y i e l d of addition products.  regiochemical  germane  Moreover,  yields  the source of Pd(0) also had no effect on the reaction  were  resulted  Increasing the amount of (PPl^^Pd to approximately 0.1 equiv  actually  the  appropriate  3  on  s i l i c a gel.  column chroma-  A v a r i e t y of functional  - 131 Table X I I :  Synthesis of a l k y l ( E ) - 2 - ( t r i - n - b u t y l s t a n n y l ) - 3 - t r i m e t h y l germyl-2-alkenoates (277) and a l k y l ( Z ) - 3 - ( t r i - n - b u t y l stannyl)-2-trimethylgermyl-2-alkenoates (278)  MejGe^  C0 R'  R  SnBu  GeMe  R  3  90  Entry  BujSn^  •H • H  • COaR'  2  277  90  3  CO R' a  278  R'  Reaction Conditions  277  278  Yield (%) 277,278  3  b  CCA) 1  70  2  115  3  98  4  118  c  5  119  d  6  121  d  Me  Et  85/24  279  280  61,19  i-Pr  Me  86-90/24  281  282  48,15  Me  92-95/5  283  284  55,15  C1CH (CH )4 2  2  tert-BuMe SiOCH (CH ) 2  2  THPOCH CH CH 2  2  2  3  2  (3 -cyclohexenyl)methyl  Me  95/14  285  286  56,14  Me  95/5  287  287  55,15  Me  100/16  289  290  53,16  A mixture of (90) (1 equiv), tri-n-butylstannyltrimethylgermane (1.0-1.5 equiv) and (PPl^^Pd (0.02-0.006 equiv) was s t i r r e d under the conditions shown. Y i e l d of p u r i f i e d , isolated product. This material was prepared procedure of Chong.  by  Dr.  B.A. Keay  according  2  These materials were prepared by Dr. J . M . C h o n g .  42  to  the  - 132 groups present i n the a,B-acetylenic  ester ( 9 0 ) were tolerated: an a l k y l  chloride (entry 3), ether functions (entries 4,5) double bond (entry 6).  the  a carbon-carbon  It should also be noted that the presence of the  f a i r l y bulky iso-propyl group (entry 2) although  and  does  not  stop  the  reaction,  y i e l d was s l i g h t l y lower than i n the other reactions.  each case (Table XII) the ^ti nmr, i r and mass spectra  are  in  In  complete  agreement with the assigned structure. The  stereochemical configurations of the addition adducts (277) and  (278) were unequivocally corroborated by performing appropriate decoupling (282)  and  nOe  difference  (entry 2, Table X I I ) .  experiments on the compounds (281) and  For example, i n the case of (281),  irradia-  282  281 tion  nmr  of the doublet at S 2.08 (M^CH-) caused collapse of the multiplet  at 6 2.33  (Me CH-) to a 2  coupling)  singlet  (with  and showed that J_Sn-H ^ 4  o r  t  n  satellite  peaks  due  to  Sn-H  l a t t e r signal i s 9 Hz, a value  e  t y p i c a l of coupling between an a-Sn atom and a -y-H i n an o,/9-unsaturated Furthermore,  ester.  irradiation  at  enhancement at 6 3.64 (-OMe) and S 1.12 3.64  6  0.33  (-GeMe.3)  (Me CH-), while i r r a d i a t i o n at 6 2  (-OMe) caused signal enhancement at S 0.33 (-GeMe.3).  hand, i n the case of (Me.2CH-)  caused  (282),  irradiation  of  the  collapse of the septet at S 2.68  doublet  latter  signal  is  80  On the other at  6  1.00  (Me2CH-) to a singlet  (with s a t e l l i t e peaks due to Sn-H coupling) and showed that the  caused signal  3  J.Sn-H  ^  o r  Hz, a value which corresponds to a coupling  - 133 between a 8-Sn atom and a 7-H i n an a,^-unsaturated irradiation  at  6  0.32  (-GeMe.3)  (-OMe), while i r r a d i a t i o n at S 3.67 6 0.32  (-GeMe ) and 6 2.68 3  (Me CH-). 2  caused  ester.  Furthermore,  signal enhancement at 6 3.67  (-OMe) caused signal enhancement  at  In addition, i r r a d i a t i o n at S 2.68  (Me CH-) caused s i g n a l enhancement at S 3.67  (-OMe) and 6 1.00  2  (Me CH-). 2  The r e s u l t s of the decoupling and nOe difference experiments are consistent only with the structures depicted i n formulas (281) Although the Pd(0)-catalyzed addition of (276) was  not  extensively  investigated  stereoisomer was obtained 1-alkyne when a  and  an  solution  treated  with  when  the  (276)  to other t r i p l e bonds  i t was found that a single regio-and addition  was  N,N-dimethyl a,8-acetylenic of  and (282).  carried  alkynamide.  N,N-dimethyl-2-butynamide  (166)  out  on  a  For example,  in  benzene  was  (1 equiv). and (PPh^^Pd and the mixture was s t i r r e d  at 80°C for 31 h, t i c analysis indicated the presence of two components. After  column chromatography of the crude o i l on s i l i c a gel two  o i l s were obtained, one of which was found to correspond to recovery).  The  more  polar  compound  was  subsequently  separate  (276)  (72%  i d e n t i f i e d as  ( £ ) - N , N- dime thy 1- 2 - t r i - n - b u t y l s t a n n y l - 3 -trimethylgermyl- 2-butenamide (291)  (equation 67) and was isolated i n 19% y i e l d .  The spectral data of  MejGe M  . - ^ C O N M „  CONMe  )=( Me  166  2  I*" SnBuj  291  t h i s compound was found to be i n f u l l accord with the assigned (see  Experimental  section).  The regiochemistry and the  structure  stereochemical  - 134 -  configuration was r e a d i l y established from the • H nmr spectrum and  from  L  nOe  difference  experiments.  For example, the  nmr spectrum of  showed a 3-proton s i n g l e t at 6* 1.92 with s a t e l l i t e coupling. 4  This  coupling  constant  peaks  the  n  Furthermore,  irradiation  enhancement at S 1.92  i r r a d i a t i o n at 5 1.92  6 0.21  (-GeMe ) and 6 0.98  at  2.90  6  3  6  3  (-NMe) and 5 2.92  at  the presence of indicated  120°C two  (-GeMe.3)  amide  func-  caused  (-NMe) and 6  2.92  Moreover,  2  2  signal (-NMe),  irradiation  (-NMe) caused signal enhancement at 6 0.98 (-GeMe.3).  When a mixture of phenylacetylene, stirred  0.21  (CH (CH2) CH )3Sn-).  2  was  Sn-H  ( v i n y l methyl) caused signal enhancement at  ( C H ( C H ) 2 C H 2 ) 3 S n - ) and S 0.21 3  at  ( v i n y l methyl), 6 2.90  while  to  is 11 Hz which is i n accord with a  J g . j j and thus establishes that the t i n atom is o to  tion.  due  (291)  (279)  (1.07 equiv) and  (PPt^^Pd  for 24 h, t i c analysis of the mixture indicated  components.  Glc  analysis  the presence of phenylacetylene.  of  an  aliquot  After column chromatography  of the black o i l on s i l i c a gel two o i l s were obtained, one of which found  to  correspond  subsequently  to  identified  methylgermylethene  Ph  (292)  (279) as  also  (67% recovery).  was  The other compound was  (Z)-1-phenyl-l-tri-n-butylstannyl-2-tri-  (27% y i e l d )  Bu SnGeMe,  (equation 68).  Bu Sn  GeMe  3  The spectral data  3  a  Pd(PPh ) 3  (68)  4  Ph  292  H  of t h i s l a t t e r material was found to be i n f u l l accord with the assigned structure  (see  Experimental  section).  The  regiochemistry  and  the  - 135 -  stereochemical using  a  showed,  configuration of  single  piece  with  was  unequivocally  of spectral data.  amongst other signals,  proton)  (292)  satellite  a  peaks  The  1-proton due  to  corroborated  nmr spectrum of  singlet Sn-H  at  6  coupling.  6.78  (292) (vinyl  The coupling  constant associated with this coupling i s 161 Hz which i s i n accord with a  "^Isn-H  (trans).  The  only  structure  in  which such a coupling i s  possible i s that shown by (292). It i s not c l e a r why the stannyltrimethylgermane completion. much  to  addition  of  esters  fails  a,B-acetylenic  However, i t i s apparent that the  greater  extent  phenylacetylene ester  Pd(0)-catalyzed  or  than  reactions  tri-n-butylto  go  proceed  to  to  a  those involving addition of n-Bu3SnGeMe3 to  N,N-dimethyl-2-butynamide  (166).  Presumably,  the  function exerts a greater electronic effect on the t r i p l e bond as  compared to an amide function or phenyl group. the Pd(0)-catalyzed  problem  that  addition of hexabutylditin to ethyl 2-butynoate  also f a i l e d to go to completion (see This  It should be noted  Section  II  of  the  (70)  Discussion).  could perhaps be overcome by changing the a l k y l groups on  t i n to a size intermediate i n size between a methyl and a n-butyl group. For  example,  if  Pd(0)-catalyzed Mitchell  4 3 0  had  triethylstannyltrimethylgermane addition reported  reaction  should  complete  go  reaction  addition of hexamethylditin to 1-alkynes.  were to be used,  to in  completion, the  Moreover,  the  since  Pd(0)-catalyzed  disproportionation  would presumably, not be a problem. ** 46  Presumably, tion would  of  a  pathway which accounts for the Pd(0)-catalyzed  tri-n-butylstannyltrimethylgermane  to  a,B-acetylenic  addiesters  be analogous to that depicted i n Scheme 19, which i l l u s t r a t e s  the  - 136 -  pathway  for  the  Pd(0)-catalyzed  a,/9-unsaturated esters.  addition  isomers  under the reaction conditions  39  (277)  (equation  Me Ge  SnBu  3  hexamethylditin  However, the i n i t i a l l y formed a l k y l  n-butylstannyl-3-trimethylgermyl-2-alkenoates to i s o m e r i z e  of  69).  (277A) to  277A  this  (Z)-2-tri-  would be expected  afford  the  geometric  The mechanistic pathway accounting for  Me Ge  3  C0 R'  3  2  8J-10P°C R  ( ) 69  C0 R'  R  2  277  SnBu  isomerization process (equation 69) is very  3  likely  analogous  that depicted for the a l k y l 2,3-bis(trimethylstannyl)-2-alkenoates see equation 23 and Scheme 20). other  isomer  (278)  Presumably, the  Bu Sn 3  H  R  278  However, the factors governing Pd(0)-catalyzed addition of (276)  respectively,  isomerization  to (e.g.  of  the  is a thermodynamically unfavourable process due to  the strength of the germanium carbon b o n d .  compounds (277)  to  and (278)  9  GeMe  3  C0 R" 2  the  regiochemical  outcome  to a , a c e t y l e n i c esters,  of  i n which the  are formed i n a r a t i o of approximately  are not c l e a r .  the  3.3:1,  It does seem apparent, though, that  steric  factors are not very important since a s i m i l a r r a t i o of 3:1 was obtained when  the  corresponding  reaction was repeated with trimethylgermyltri-  methyltin on the substrate ethyl 2-butynoate  (70).  It  should  also  be  - 137 noted that even with a substrate containing the f a i r l y bulky group 3:1,  (entry  iso-propyl  2, Table X I I ) , the r a t i o of (281):(282) was approximately  respectively. F i n a l l y , the factors governing  Pd(0)-catalyzed addition of (276)  the  regiochemical  outcome  of  the  to N..N-dimethyl-2-butynamide (166) and  phenylacetylene are not c l e a r .  B.  Spectral data of a l k y l (E)-2-(tri-n-butvlstannyl)-3-trimethylgermvl2-alkenoates and a l k v l  (Z)-3-(tri-n-butvlstannyl)-2-trimethylgermvl-  2-alkenoates  Unlike the case of a l k y l nmr  spectroscopy  was  configuration of the  not title  2,3-bis(trimethylstannyl)-2-alkenoates, useful  in  determining  compounds.  In  the stereochemical  particular,  the  chemical  s h i f t s of the 7 protons i n the l a t t e r compounds did not vary appreciably within a given p a i r of isomers.  This is i n contrast to the a l k y l  bis(trimethylstannyl)-2-alkenoates However, i t was found that tool  for  corroborating  (278), although pronounced alkenoates  as  the in  (see Table I I I ) . nmr spectroscopy d i d provide a useful  the stereochemical configurations of (277) and  differences the  case  (Tables IV and  V).  in  the  of the a l k y l  For instance,  spectral  data  are  not  as  2,3-bis(trimethylstannyl)-2-  Nevertheless,  summary of some useful data observed i n the (277) and (278).  2,3-  Table  XIII  contains  a  nmr spectra of compounds  i f one considers the chemical s h i f t s  of  the carbonyl carbon (6*C ) (Table XIII) the values range from 161.3-166.9 A  Table X I I I :  Selected  1  3  C nmr data  compounds (277)  and  A C0 R'  Me Ge 3  R  for  Bu Sn  2  SnBu  D  (278)  RD  3  277  R  277/ 278  (6C )  («C )  (*C )  («C )  E Z E Z E Z E  279 280 281 282 283 284 285 286 287 288 289 290  161. 3 155. 6 166. 9 168. 0 166. 4 160. 8 166. 9 161,,2 166..1 160,.6 166..8 160 .0  146. 0 149. 8 145. 0 146. 4 145.,9 149..2 145. 5 148..9 145..6 149..5 147 .0 149 .8  172.,5 171, 8 173..1 172. 8 172..9 172 .2 173..0 172,.3 172..8 172 .2 172 .6 172 .3  26..6 26..7 44..6 40,.2 41 .9 40 .9 42 .0 41 .1 38 .8 38 .0 48 .4 47 .9  Me  Et  2  i-Pr  Me  3  C1CH (CH )  4  tert-BuMe S10CH (CH )  5  THPOCH CH CH  Me  6  (3 -cyclohexenyl)methy1  Me  2  3  Me  A  2  2  2  2  2  3  2  Me  z  E Z E Z  B  A  J.Sn-C  Conflguration  1  2R  8  R'  A  3  CO . 278  Chemical S h i f t Entry  GeMe  3  C  D  C  (2 n-C > D S  n  50 48 52 44 47 46 47 44 47 46 44 44  d  (^Sn-C,)' 1 326 320 325 317 328 320 331 320 327 320 327 320  b  ( ISn-cJ 2 2  20 19 20 18 20 18 19 18 20 20 19 18  f  < .lSn-C,> 3 3  60 60 62 67 61 62 Jh 64 61 64 61 65  g  Chemical s h i f t  (6) was measured r e l a t i v e to the deuteriochloroform signal  (5 7 7 . 0 ) ° 0 i n ppm.  A l l spectra were recorded on deuteriochloroform  Coupling constants i n Hz.  In a l l cases apart from dsn-C^)  t  n  e  solutions.  value quoted i s  obtained from the centres of the unresolved H^Sn and H^Sn s a t e l l i t e s . {(Cp) refers to the chemical s h i f t of the a l l y l i c carbon 7 to the ester function. J_Sn-C refers to J.Sn-C  ( £ ) isomers (277)  and to J_Sn-C ^  Me Ge  C0 R'  Bu Sn  D  SnBu  3  n  isomers (278)  n  ^  o r  t  n  C  3  '• 1  2  J_5 _C : n  2  3  Jg _C : n  3  2  n  o r  t  b  e  ^—^  e.g. 3  ^Sn-C  e  iSn-C  2  D  =  3  3  J n-C S  3  n  (cis)  D  coupling between the t i n atom and the adjacent carbon of the n-butyl group. In this case the value quoted is an average of the value for the H^Sn and H^Sn s a t e l l i t e s which were resolved separately. coupling between the t i n atom and the second nearest carbon of the n-butyl group. coupling between the t i n atom and the t h i r d nearest carbon of the n-butyl group.  This signal could not be measured.  - 140 ppm for the (E) isomers (compounds (277)) and from 155.6-168.0 the (Z) isomers (compounds (278)).  ppm  for  As i n the case of a l k y l 2 , 3 - b i s ( t r i -  methylstannyl) -2-alkenoates , the chemical s h i f t s of the carbonyl carbons (5C )  of the (E) isomers are further downfield when compared to those of  A  the corresponding (Z) isomers. in  For example, for the compounds appearing  entry 1 (compounds (279), (280)) the chemical s h i f t s of the carbonyl  carbons (6C , Table XIII) are S 161.3 ((E)  isomer)  A  isomer), respectively.  and  6  155.6  ((Z)  This i s consistent for a l l examples presented i n  Table X I I I , apart from the compounds given i n entry 2 (R - i.-Pr) . It i s of interest to note that the chemical s h i f t s carbons  (5Cg)  and  (SCQ) are  of  the  vinylic  almost i d e n t i c a l with the corresponding  values for the a l k y l 2,3-bis(trimethylstannyl)-2-alkenoates  (Table  IV).  The chemical s h i f t of (SCg) was found to decrease by approximately 3 ppm i n going from the (Z) isomer (277).  (278)  to  the  corresponding  (E)  isomer  A s i m i l a r pattern is apparent i n Table IV.  Table  XIII also contains a summary of tin-carbon coupling constants  observed i n the  1 3  C nmr spectra of compounds  (277)  (278).  These  constants  range  ( Jg _c).  It can be noted that for a l l examples (except those given  entry  the  3  n  2)  2  from one bond coupling (^slsn-c)  and  2sn-C  3  v  a  l  u  e  i  n  r  e  bond coupling  e  s  5  For instance, i n the examples given by 0  H  z  f  o  r  t  h  in  i n which i t  of  alkyl was noted  entry  isomer (279) and the J.sn-C  e  2  n  that made i n the case  (cis)  t  3  value i s 48 Hz for the (Z) isomer (280).  (Table V ) ,  o  values (compounds (278)) are close to the J_sn-C  values (compounds (277)). 1, the J_sn-C  t  D  This observation i s s i m i l a r to  2,3-bis(trimethylstannyl)-2-alkenoates that J.Sn-Cp 2  for most of the cases l i s t e d i n Table V.  w  a  s  t  n  e  s  a  m  e  a  s  ^Sn-C  D  F i g . 10:  The 75.6 MHz  i J  C nmr and APT spectra of (285)  - 142  -  GeMe  Bu Sn  3  3  C0 Me 2  Bu Me SiO !  2  b  c  a  J  -rrp 200  Fig.  ' ' I ' '  180  11:  mm  The  75.6  120  140  MHz  1 3  T 80  1  i i I i i i  i|  i i  60  C nmr and APT s p e c t r a o f  i | 1i1 i  1 1  m  40  (286)  1111111 20  I I I I I  1  I' 0  1 1  1 1 1 1  PPM  - 143 -  C0 R'  Me Ge 3  C  2  °  SnBu  B  u Sn 3  3  ^Sn-Cjj (cis) Finally,  the tin-carbon coupling constants between the t i n atom and  the carbons of the n-butyl As expected,  group (^slsn-C^  the ^ S n - C ^ values  t  ^-Sn-C-j) deserve comment.  o  (coupling between the  t i n atom and the  adjacent carbon of the n-butyl group) are the largest,  the average value  being 320 Hz.  However,  next  the  largest,  values  the J_s -c.j 3  n  average value  values  (3-bond coupling)  being 60 Hz,  followed by the J.Sn-C2 2  (2-bond coupling), the average value being 20 Hz.  These  values are consistent with those reported i n the l i t e r a t u r e . The  1 3  C  nmr  are the  latter  8 9  spectra depicted i n Figures 10 and 11 serve to i l l u s -  trate the features discussed i n this section of the t h e s i s .  C.  Chemistry of ethyl butenoate  (E)-2-(tri-n-butvlstannyl)-3-trimethvlgermvl-2-  (279)  Having established a route for the preparation of a l k y l n-butylstannyl) -3-trimethylgermyl-2-alkenoates to determine the synthetic u t i l i t y of these viously  a  (E)-2-(tri-  program was i n i t i a t e d  substances.  We had  shown (Section I I I . A of the discussion of this thesis) that the  a-SnMe3 group of a l k y l 2,3-bis(trimethylstannyl)-2-alkenoates removed  pre-  could  be  chemoselectively by transmetalation with methyllithium and that  - 144  -  the r e s u l t a n t  nucleophilic  variety  of  electrophiles  to a f f o r d t r i s u b s t i t u t e d v i n y l s t a n n a n e s (Table V I I I ) .  As  a consequence, our i n i t i a l such  as  (279)  in  intermediate  reacted  with  a  o b j e c t i v e i n p r o b i n g the u t i l i t y  synthesis,  o f compounds  was to determine the f e a s i b i l i t y o f  the  corresponding transmetalation-alkylation r e a c t i o n . As  expected,  reaction  of  it  was  compound  example, a s o l u t i o n o f n-butyllithium  found  (279) (279)  ( i n hexane)  that  was in  at  the  transmetalation-alkylation  a f a c i l e and e f f i c i e n t p r o c e s s .  THF  was  treated  - 9 8 ° C f o r 20 m i n .  with  1.2  After  the  mixture  had  ammonium c h l o r i d e , g l c and t i c p r e s e n c e o f two components. gel,  quenched  analyses  of  with  the  to  tetrabutyltin,  was s u b s e q u e n t l y germyl-2-butenoate material  was  identified (294)  isolated  solution  ethyl  the  attributable  ir  e t h e r ) was  3  found  to  0.37)  A f t e r a p p r o p r i a t e workup,  in  The s p e c t r a l d a t a o b t a i n e d from  80% y i e l d .  of  (294)  C0 Et  structure.  this  For  showed an a b s o r p t i o n a t 1713 c m "  2  3  ,-98°C  (70)  Me 294  1  a.^-unsaturated  C0 Et  *Me Ge 1.n-BuLI,THF,-98 C e  Me  (silica  ( e q u a t i o n 70).  spectrum  2  the  (Z)-2-(2-propenyl)-3-trimethyl-  to the c a r b o n y l s t r e t c h i n g f r e q u e n c y o f an  Me Ge  40  showed  w h i l e the more p o l a r compound (Rf as  of  s a t u r a t e d aqueous  was found to be i n f u l l a c c o r d w i t h the a s s i g n e d  example,  -98°C for  The l e s s p o l a r compound (Rf — 0.90)  development w i t h 95:5 p e t r o l e u m e t h e r - d i e t h y l  correspond  (294)  been  equiv  3-Iodopropene was added  to the p a l e y e l l o w s o l u t i o n and the mixture was s t i r r e d at min.  For  - 145 ester  function.  at 5 0.27, at  6  dd  showed a 9-proton singlet  (J - 7 Hz), a  a 2-proton doublet at 6 3.16  3-proton  (J - 10, 2 Hz), a 1-proton  (J - 17, 2 Hz) and a 1-proton ddt at 8 5.78  (J - 17, 10, 6  Furthermore, high resolution mass spectrometry v e r i f i e d  molecular formula of (294) The  results  in  of reactions involving the use of (279)  yields  (entries  XIV.  1-3),  When reactive  These  (entry  reactions  alkylating  4)  was  agent,  employed  for  pro-  agents  were  reaction,  example,  1-chlo-  the y i e l d was only 42%.  should be noted that, i n each case (Table XIV), the transmetalation  and some other  the y i e l d s of substitution product were good.  However, when a less reactive a l k y l a t i n g ro-3-iodopropane  by-product  of  the  sole  It the  t e t r a b u t y l t i n , was r e a d i l y removed by column  chromatography of the crude o i l on s i l i c a g e l , affording the ester as  the  ranging from 42% to 77%, although i n these cases the  y i e l d s have not been optimized. employed  that  is 0-12^2^2^ •  a l k y l a t i n g agents are summarized i n Table ceeded  singlet  (J = 6 Hz), a 2-proton quartet  (J - 7 Hz), a 1-proton dd at 8 4.96  at 8 4.98  Hz).  nmr spectrum of (294)  a 3-proton t r i p l e t at 6* 1.27  1.90,  at 6* 4.15  The  substitution  product.  (293)  A l l compounds shown i n Table XIV  exhibited ^H nmr, i r and mass spectra i n f u l l accord with  the  assigned  structures. As  expected, based on the results of the transmetalation-alkylation  reactions of a l k y l sponding  2,3-bis(trimethylstannyl)-2-alkenoates,  reactions  with  (279)  proceeded  transmetalation  allenoate a n i o n  3 9  of  (279)  (298), which alkylates  corre-  to afford adducts (293), i n  which the trimethylgermyl group and the ester function are Presumably,  the  leads from  to the  the side  cis-related.  formation of an opposite  the  - 146 -  T a b l e XIV:  T r a n s m e t a l a t i o n o f methyl ( E ) - 2 - ( t r i - n - b u t y l s t a n n y l ) - 3 - t r i methylgermyl-2-butenoate (279) and r e a c t i o n s o f the r e s u l t a n t intermediate with e l e c t r o p h i l e s  Me Ge  C0 Et  3  Me  Entry  2  \  /  /  \  SnBu  279  EX  3  Me Ge 1.n-BuLI,THF,-98"C \  C0 Et  3  2.EX,-98°C  Me  3  b  2  /  / 293  V E  293  Yield  1  CH =CHCH I  294  80  2  Mel  295  77  3  Me C=CHCH Br  296  74  C1CH CH CH I  297  42  4  2  2  2  d  2  2  2  2  (%)  c  R e a c t i o n c o n d i t i o n s : A s o l u t i o n (THF, - 9 8 ° C ) o f (279) was treated w i t h n - B u L i ( 1 . 1 - 1 . 2 e q u i v ) , the mixture was s t i r r e d a t - 9 8 ° C (15-20 m i n ) , EX was added, the mixture was s t i r r e d a t - 9 8 ° C f o r up to 45 min and then quenched (NH4C1-H 0). 2  These m a t e r i a l s were passed through a column o f a c t i v i t y I b a s i c alumina immediately p r i o r to u s e , w i t h the e x c e p t i o n o f l-bromo-3methyl-2-butene ( e n t r y 3), which was d i s t i l l e d immediately p r i o r to use. Y i e l d of p u r i f i e d , In t h i s r e a c t i o n ,  d i s t i l l e d product. the r e a c t i o n mixture was warmed t o  -78°C.  - 147 bulky  trimethylgermyl group, thus affording a single stereoisomer  (equation  71).  Me Ge 3  C0 Et  H  Me Ge  2  Me  SnBu  3  OEt  Me  3  (293)  was  OLI  configuration  of  unequivocally  to  the  established  by  performing  example.  (CH =CHCH -), 2  2  ,71)  E 293  substitution a  Thus, i n the  (294), i r r a d i a t i o n of the s i n g l e t at 5 1.90  caused s i g n a l enhancement at 5 5.78 and 5 0.27  Me  2  assigned  difference experiment on a representative spectrum  C0 Et  3  298  stereochemical  products  Me Ge  )—< •«—H  279 The  (293)  6  nOe nmr  ( v i n y l methyl)  5.16  (CH =CHCH -) 2  2  (-GeMe ). 3  Me  3  294 Interestingly,  when  ethyl  (Z)-3-(tri-n-butylstannyl)-2-trimethyl-  germyl-2-butenoate  (280) was treated  and  a  iodomethane,  result  quite  successively different  for  Iodomethane was added and the solution was s t i r r e d at  45 min and at -78°C for 45 min.  single product was i s o l a t e d i n 75% quently i d e n t i f i e d as ethyl germyl-3-butenoate (299)  Thus, a s o l u t i o n of  i n THF was treated with 1.2 equiv of n-butyllithium ( i n hexane) at  -98°C for 15 min. -98°C  n-butyllithium  from that derived from a  s i m i l a r procedure with compound (279) was observed. (280)  with  (299)  yield.  After appropriate workup, a This  material  was  subse-  2-methyl-3-(tri-n-butylstannyl)-2-trimethyl-  (equation 72).  The spectral data derived  were found to be i n f u l l accord with the assigned structure.  from For  - 148 -  Bu Sn 3  H  Me  GeMe  C0 Et 2  SnBu  3  1. n-BuLI,THF,-98°C 2. Mel,-98° — -78°C 3.NH CI  3  (72) C0 CH H CH' 2  c  D  3  4  Me Ge  280  Me  3  299 example, the i r spectrum showed an absorption at 1681 cm to  attributable  the carbonyl stretching frequency of the ester function.  spectrum of (299), i n addition to the signals due stannyl  group,  at S 1.41, 4.17  to  the  showed a 9-proton singlet at S 0.20,  a 1-proton dq at 6 4.06  The -"-H nmr tri-n-butyl-  a 3-proton s i n g l e t  (J - 11, 7 Hz), a 1-proton  (J - 11, 7 Hz), a 1-proton doublet at 6 5.27  68 Hz) and a 1-proton singlet at 5 5.66  dq  at  6  (J - 1.5 Hz, J_s -H 3  =  n  (J •= 1.5 Hz, J_s -H 3  =  1  4  6  Hz  n  ^'•  Furthermore, high resolution mass spectrometry showed that the molecular formula of (299) i s  C 2H46°2 ^ G  S n  2  Presumably, the s t e r i c a l l y hindered nature of the t r i - n - b u t y l s t a n n y l group of (280) hinders the transmetalation of this moiety. hand, i t i s the strength of the germanium-carbon bond^ for  On the other  which  accounts  the lack of r e a c t i v i t y of the trimethylgermyl group of (280) towards  the transmetalation process. n-butyllithium anion.  led  to  treatment of (280)  As a consequence,  with  the deprotonation of (280) affording an enolate  This species upon treatment with iodomethane afforded  (299)  as  the sole s u b s t i t u t i o n product. With  a  f a c i l e synthesis of t r i s u b s t i t u t e d vinylgermanes of general  structure (293) at hand, our utility  of  next  objective  these compounds for synthesis.  was  Successive  investigate  the  In p a r t i c u l a r , we envisaged  conversion of the ester moiety of (293) into the (300).  to  corresponding  alcohol  manipulation of this l a t t e r material, by a sequence  - 149 -  of  s t e p s s i m i l a r to t h a t d i s c u s s e d  thesis,  could either  in  a f f o r d the e t h e r  (X = h a l o g e n ) .  I t may be n o t e d t h a t  equivalent  the  to  the  d,a  previous  (301)  (302)  section  of  this  o r the a l l y l i c h a l i d e  (302)  is potentially  synthetically  synthon r e p r e s e n t e d by s t r u c t u r e  (303)  (Scheme  25).  Me Ge  C0 Et  3  Me Ge  2  y— OH  3  r\  I  j— X  r\  r=\  Me  E  Me  E  293  Me  E  300  H  Me  302  E  'A Me  E 303  301 Scheme 25  As e x p e c t e d , to  the  allylic  solution of at  0°C  isolated  for  (294) 2  the r e d u c t i o n o f the e s t e r f u n c t i o n o f compounds alcohols  (300)  was a f a c i l e p r o c e s s .  i n e t h e r was t r e a t e d w i t h DIBAL a t h.  After  i n 100% y i e l d .  appropriate  T h i s substance  workup,  d a t a d e r i v e d from t h i s  -78°C for 1  a single  e  3  °  e  Me  \  /  / — °^  \ 304  _  /  '  h  a  and  compound was  identified  (304).  compound was found to be i n f u l l  M  For example,  was s u b s e q u e n t l y  (Z)-2-(2-propenyl)-3-trimethylgermyl-2-buten-l-ol  (293)  as  The s p e c t r a l  accord with  the  - 150 assigned  structure.  For  example,  the  ir  spectrum  showed  a broad  absorption at 3336 cm" attributable to the O-H stretching frequency  of  1  an  alcohol  function.  The ^H nmr spectrum of (304)  showed, i n addition  to the signals due to an a l l y l group, a 9-proton s i n g l e t at broad  0.30,  a  1-proton s i n g l e t i n the region 6 1.51-1.60, a 3-proton s i n g l e t  at  S 1.79 and a 2-proton s i n g l e t at 6 4.09. mass  spectrometry  showed  that  the  Furthermore,  molecular  S  high  formula  resolution  of  (304)  is  C H OGe. 10  20  The (305)  subsequent conversion of was  readily  (304)  accomplished.  into  Thus,  the  when  corresponding  ether  a solution of (304)  in  CH2CI2 was treated with methoxymethyl chloride and N,N-diisopropylethylamine  and  the  mixture  was  s t i r r e d at room temperature for 23 h, the  ether (305) was i s o l a t e d i n 66% y i e l d  after  appropriate  workup.  The  305  s p e c t r a l data derived from this compound were found to be i n f u l l accord with the assigned structure. clearly  showed  For example, the ^H nmr spectrum of  (305)  the presence of a methoxymethyl ether moiety which gave  r i s e to a 3-proton s i n g l e t at S 3.40,  a 2-proton s i n g l e t at S 4.01 and a  2-proton s i n g l e t at 6 4.63. In  analogy  to  vinylstannanes,  metal-iodine exchange. ^ 9  treated  with  iodine,  Thus, when and  vinylgermanes  also undergo f a c i l e  a solution of (305)  i n CH2CI2  was  the mixture was s t i r r e d at room temperature  u n t i l a pale purple color persisted, the iodide (306)  was  isolated  in  - 151 83%  y i e l d after appropriate workup.  S i m i l a r l y , treatment of a solution  of the alcohol (304) i n CH Cl2 with iodine, afforded the iodide (307) i n 2  72% y i e l d .  The spectral data derived from (306) and (307) were found to  be i n f u l l accord with the assigned structure.  306  307  The stereochemical configuration of (306) and cally  (307)  was  unequivo-  established by performing a nOe difference experiment on compound  (306).  For example,  caused  signal  i r r a d i a t i o n of the s i n g l e t at 6 2.57  enhancement  at  6 5.05  ( v i n y l methyl)  ( v i n y l proton) and 5 5.75  (vinyl  proton). We were pleased to find that the alcohol (307)  could  smoothly into.the corresponding a l l y l i c bromide ( 3 0 8 ) .  be  converted  Thus, a solution  of the alcohol (307) i n CH2CI2 was added dropwise to a solution of phenylphosphine  and bromine  91  at - 2 0 ° C .  tri-  After the reaction mixture had  been warmed to room temperature, t i c analysis of the solution showed the presence of only one component (Rf = 0.70) 95:5 petroleum ether-diethyl bromide  (308)  was  isolated  ether).  ( s i l i c a g e l , development with  After  appropriate  i n 92% y i e l d (equation 73).  workup,  the  The spectral  data derived from (308) were i n f u l l accord with the assigned structure.  (73) 307  308  - 152 -  For  example,  the  ^-H nmr spectrum of (308)  signals due to an a l l y l group, a 2-proton  singlet  4.20.  S  at  3-proton  showed, i n addition to the  singlet  Furthermore,  high  resolution  spectrometry showed that the molecular formula of (308) The u t i l i t y of compound (308)  2 . 5 8 and  S  at  is  as an intermediate for  the  formation thesis.  Synthesis of b i c y c l i c and t r i c y c l i c r i n g systems  As  discussed  in  section  c y c l i c 6-trimethylstannyl alkyl  I I I . A of this thesis, the preparation of  a,^-unsaturated  esters from the  w-halo-2,3-bis(trimethylstannyl)-2-alkenoates  f a c i l e process. the  mass  C-JU^QBTI.  of b i c y c l i c dienes w i l l be discussed i n the next section of t h i s  V.  a  was  The former materials had been u t i l i z e d  development  of a new annulation sequence.  63  previously  for  8-trimethylstannyl  ( i n which n = 1 or 2 ) could be trapped with (equation 7 4 ) .  a l k y l a t i n g agents to afford compounds (309) SnMe  shown to be a  In p a r t i c u l a r , i t had  been shown that the enolate anion derived from c y c l i c a,y9-unsaturated esters (203)  corresponding  6 3  Thus,  it  3  C0 Me LDA-THF-HMPA 2  I  ** *V>C0 Me s  j (74)  2  EX  was  envisaged  that a l k y l a t i o n of compounds (203) with an appropriately  functionalized a l k y l a t i n g agent such as (308) equivalent compounds  to of  the  d,a  general  (potentially  synthetically  synthon (310)), could lead to the formation of structure  (311).  Conceivably,  these  latter  - 153 compounds,  on the basis of S t i l l e ' s work,  Pd(0)-catalyzed cross-coupling of the functions  to  2  could undergo intramolecular  vinylstannane  and  vinyl  iodide  a f f o r d b i c y c l i c dienes of general structure (312)  (Scheme  26).  310  312  Me  Scheme 26  We were pleased to find that the a l k y l a t i o n of compounds (203) the  alkylating  agent  (308)  was  a  facile  process.  For example, a  s o l u t i o n of methyl 2-trimethylstannyl-l-cyclohexenecarboxylate THF  was  treated  -20"C  for 30 min.  HMPA  (3  equiv)  with  The yellow solution  was  analysis  showed  reaction  component (Rf - 0.42) ether-diethyl (313).  successively  (15 min) and the a l k y l a t i n g agent: (308) aqueous  the  ether),  mixture  (silica which  gel, was  ammonium the  in  development  treated (-20°C,  with  30 min)  chloride.  Tic  presence of one major with  95:5  petroleum  subsequently i d e n t i f i e d as the ester  After appropriate workup, the ester (313) was  y i e l d (equation 75).  (206)  a solution of lithium diisopropylamide (THF) at  and then was quenched with saturated of  with  isolated  in  66%  The spectral data derived from (313) were found to  - 154 -  be In f u l l accord with the assigned spectrum  structure.  For  example,  the  showed an absorption at 1733 cm" attributable to the carbonyl 1  stretching frequency of an ester function and an absorption at 769 attributable group. to  ir  The  the  to  1  the tin-methyl rocking frequency of a trimethylstannyl  nmr spectrum of (313)  allyl  cm"  showed, apart from the signals  a 9-proton singlet at 6 0.15  group,  3-proton multiplet i n the region S 1.60-1.79, a  ( J_s -H "° ^ 2  n  3-proton  4  due  Hz), a  multiplet  in  the region 6 2.01-2.16, a 3-proton s i n g l e t at 5 2.55,  a 1-proton doublet  at S 2.56  ( J =  ( J = 14 Hz), a 1-proton doublet at S  3.00  3-proton s i n g l e t at S 3.69 and a 1-proton t r i p l e t at S 5.99  14  Hz),  a  ( J = 3.5 Hz,  o  J_Sn-H — 74 Hz).  Furthermore, high resolution mass spectrometry  that the molecular formula of (313) The  Pd(0)-catalyzed  Thus,  i s C^gH2g02lSn.  cross-coupling  v i n y l iodide (313) was found to  showed  be  a  reaction of the vinylstannanesmooth  and  efficient  process.  a solution of triphenylphosphine, triethylamine and palladium(II)  acetate i n CH3CN mixture  was  55  was added to a solution of (313)  stirred  at  80°C  for  4  h,  tic  (Rf  — 0.28)  e t h e r - d i e t h y l ether). isolated  i n 81% y i e l d .  (silica  gel,  CH3CN  and  the  analysis of an aliquot  indicated the absence of s t a r t i n g material and the component  in  presence  of  a  new  development with 95:5 petroleum  After appropriate workup, the  triene  (314)  was  The spectral data derived from (314) were found  - 155 to be i n f u l l accord with the assigned structure. spectrum  example  the  apart  from  the  signals  due  The  to  nmr spectrum of  an  1.71-1.79,  a 3-proton s i n g l e t at S 1.73,  2.39  multiplet  in  at  S  3.65,  2.20-2.31,  and  (J = 16 Hz),  a 1-proton t r i p l e t at 6 5.47  addition, high resolution mass spectrometry showed formula of (314)  5  a  the region 6* 2.33-2.42, a 1-proton doublet at 6  (J = 16 Hz), a 1-proton doublet at S 2.68  singlet  region  a 1-proton multiplet i n the  region S 2.05-2.16, a 1-proton multiplet i n the region 1-proton  (314)  a l l y l group, a 2-proton  multiplet i n the region 6 1.43-1.52, a 1-proton multiplet i n the S  ir  showed an absorption at 1728 cm"! attributable to the carbonyl  stretching frequency of an ester function. showed,  For  that  a  3-proton  (J = 4 Hz). the  In  molecular  is C15H20O2.  Me0 C 2  Me 314  It  should  be  noted  that  when the Pd(0)-catalyzed  reaction described above was performed i n clean  THF, the  cross-coupling  reaction  was  not  since t i c analysis of the reaction mixture indicated the presence  of other u n i d e n t i f i e d components.  As a consequence,  the i s o l a t e d  yield  of (314) was lower (38%), compared to when the reaction was performed i n CH3CN (81%). the  isolated  On the other hand, when the reaction was performed i n DMF yield  of  (314)  was  72%.  Although the effect of using  a l t e r n a t i v e sources of Pd(0) was not extensively found  that  when  (PPV^^Pd  investigated,  it  was  was employed, t i c analysis of the reaction  - 156 mixture indicated the presence of unidentified components. By  u t i l i z i n g a sequence of steps analogous to those described above  the triene (316) was preparedanion  derived  from  heptenecarboxylate  Thus, when a THF solution of the enolate  treatment  of  methyl  2-trimethylstannyl-l-cyclo-  (207) with LDA, was successively  and the a l k y l a t i n g agent (308)  treated  CH3CN  solution  of  (315)  with  a  the  triene  appropriate workup compounds  (315)  (316)  (equation  and  (316)  as  the  1€) . were  Treatment  of  solution of triphenylphosphine,  triethylamine and palladium(II) acetate i n CH3CN for 2.5 h afforded  HMPA  at -20°C for 1 h, the corresponding ester  (315) was i s o l a t e d i n 51% y i e l d after appropriate workup. an  with  only The  found  product spectral  at  70-75°C,  i n 85% y i e l d after data  derived  from  to be i n f u l l accord with the  as s i gne d s true ture s.  (76)  S i m i l a r l y , when a THF solution of the treatment  of  enolate  at  -20°C  was  (205)  alkylating  agent  The  spectral  data  derived  from  found to be i n f u l l accord with the assigned structure.  example, the ^H nmr spectrum of (317)  ddd  For  showed, apart from the signals due  to the v i n y l group, a 9-proton s i n g l e t at S 0.17 1-proton  the  from  for 1 h, the corresponding ester (317) was i s o l a t e d i n  66% y i e l d after appropriate workup. (317)  derived  methyl 2-trimethylstannyl-l-cyclopentenecarboxylate  with LDA, was successively treated with HMPA and (308)  anion  (^isn-H  *° -*4  Hz),  at S 2.0 (J = 13, 8, 4 Hz), a 1-proton ddd at 6 2.29  a  (J =  - 157 -  13, 8, 6.5 Hz), a 2-proton 1-proton  doublet at S 2.50  1-proton dd at 6 2.67 15.5,  multiplet  6.5  Hz),  a  in  the  region  Hz).  In  2.44-2.61,  a  (J = 14 Hz), a 3-proton s i n g l e t at S 2.55,  (J - 15.5, 1-proton  6.5 Hz), a 1-proton dd at J 3.02 . (J  doublet at 6 3.04  a -  (J = 14 Hz), a 3-proton  s i n g l e t at S 3.68 and a 1-proton t r i p l e t at 6 5.98 38  S  (J - 2.5 Hz, J g . H 3  n  addition, high resolution mass spectrometry v e r i f i e d that  the molecular formula of (317)  is C^yH2702lSn.  317 When an CH3CN solution of (317)  was  treated  with  a  solution  of  triphenylphosphine, triethylamine and palladium(II) acetate i n CH3CN for 30 h at 6 5 - 7 0 ° C , components.  t i c analysis of an aliquot showed the presence  The  less  polar  component  was  i d e n t i f i e d as the triene (318).  t h i s material was i s o l a t e d i n 55% y i e l d . is  lower,  compared  to  the  diene  system  in  polar  Although the  spectral  data  derived  yield  previous two examples (314)  the  from  bicyclo[3.3.0]nonadiene  (318)  were  was  of  (318)  and (316),  associated  inherent s t r a i n could account for the lower y i e l d of the The  component  After appropriate workup,  should be noted that there i s considerable s t r a i n conjugated  two  found to correspond to a  mixture of u n i d e n t i f i e d compounds, while the more subsequently  of  with  (318).  ring  it the  This  closure.  i n f u l l accord with the  assigned structure. A further p o s s i b i l i t y that we envisaged was to transform the  cyclic  - 158 -  318 a,^-unsaturated  B-trimethylstannyl of  general  equivalent  structure to  the  d,a  (319),  (321),  which  upon  e  esters (203)  which  synthons  compounds (203) with compounds products  M  are  (320).  (319)  transformed into t r i c y c l i c dienes of  potentially  synthetically  Conceivably,  a l k y l a t i o n of  would  subjection  into a l k y l a t i n g agents  afford  the  corresponding  to a Pd(0) c a t a l y s t ,  general  structure  would be  (322)  (Scheme  27).  Scheme 27  The preparation of compounds of general structure (319) was found to be an e f f i c i e n t  process.  For example, when a s o l u t i o n of methyl  methylstannyl -1-cyclopentenecarboxylate  (205)  2-tri-  i n ether was treated with  DIBAL at -78°C for 1 h and 0°C for 2 h, the corresponding alcohol  (323)  - 159 was i s o l a t e d i n 100% y i e l d after appropriate workup. (323)  showed a broad absorption at 3343 cm"!  stretching frequency of an alcohol function.  The i r spectrum of  attributable  to  i n an i s o l a t e d y i e l d of 88%.  the  the  323  324  derived from compounds (323), (324)  The  and (325)  are i n  The spectral data full  with  compounds (203) with the a l k y l a t i n g agent  (325)  structures.  alkylation  of  For example,  a  (205)  solution in  with a s o l u t i o n of l i t h i u m diisopropylamide at -48°C for solution  was  ( - 4 8 ° C , 30 min)  saturated aqueous ammonium c h l o r i d e .  and  then  with  workup,  THF was treated 30  min.  The  the  was  quenched  0.34)  (silica  95:5 petroleum ether-diethyl ether) and a minor  less polar component (Rf = appropriate  methyl  T i c analysis of the reaction  mixture showed the presence of one major component (Rf = development  of  successively treated with HMPA (3 equiv, 10 min),  and the a l k y l a t i n g agent (325)  gel,  of  325  2-trimethylstannyl-1-cyclopentenecarboxylate  with  at  accord  was found to be a f a c i l e process.  yellow  bromine  High resolution mass spectrometry  showed that the molecular formula was CgH3BrI.  the assigned  (324)  corresponding bromide (325) was isolated i n 80% y i e l d after  appropriate workup (equation 77).  (325)  iodide  When a solution of the iodide  i n CH2CI2 was added to a solution of triphenylphosphine and -20°C,  0-H  Treatment of a solution of  the alcohol (323) with iodine at room temperature, afforded (324)  the  0.68),  which  was  not  identified.  After  major component was i s o l a t e d i n 64% y i e l d and  -  160 -  was s u b s e q u e n t l y i d e n t i f i e d  as  derived  found to be i n f u l l  from  structure. cm"  (326)  F o r example,  attributable  1  were  the i r  to  the  the  ester  (326).  The  SnMe  data  a c c o r d w i t h the a s s i g n e d  spectrum showed an  carbonyl  spectral  absorption  stretching  at  1734  f r e q u e n c y o f an e s t e r  3  326 f u n c t i o n and an a b s o r p t i o n at 771 c m " rocking (326)  Hz),  8 1.79  (J -  13,  7,  2.27  (J = 14 H z ) ,  2 - p r o t o n ddd a t  6 2.51  region 8 2.60-2.70,  5 0.19  6.5.Hz),  a 2-proton multiplet 6  attributable  of a trimethylstannyl  showed a 9 - p r o t o n s i n g l e t a t  ddd a t  at  frequency  1  group.  The  ( J_s -H 2  a 2-proton quintet  i n the r e g i o n 8 2 . 0 8 - 2 . 2 4 , a 1-proton  (J -  7,  6.5,  ddd at 6 2.37 2 Hz),  a 1 - p r o t o n d o u b l e t at 6 2.90  (326)  triethylamine  the m i x t u r e was s t i r r e d a t  ether).  a 1-proton 7,  6.5  (J = 2 H z ,  a  is  starting  Hz), in  and  palladium(II) acetate  C  tic  the  3-proton ^isn-H  =  that  analysis  in  tri-  CH3CN and  indicated  the  and the presence o f one major component  ( s i l i c a g e l , development w i t h 95:5  After  a  C^gH2502lSn.  80 C f o r 24 h ,  material  7.5  doublet  CH3CN s o l u t i o n o f (326) was t r e a t e d w i t h a s o l u t i o n o f  phenylphosphine,  0.20)  (J -  h i g h r e s o l u t i o n mass s p e c t r o m e t r y v e r i f i e d  the m o l e c u l a r f o r m u l a o f  (Rf -  l^proton  at 6 1.89  (J = 14 H z ) ,  Furthermore,  of  a  a 2-proton m u l t i p l e t  37  absence  tin-methyl  nmr spectrum o f  (J = 13,  6 3.67 and a 1 - p r o t o n t r i p l e t at 8 5.99  When an  the  ^4 H z ) ,  =  n  s i n g l e t at Hz).  to  a p p r o p r i a t e workup,  the d i e n e  petroleum (327)  ether-diethyl  was i s o l a t e d i n 68%  - 161 yield.  The  spectral  the assigned structure. showed  data derived from (327) were i n f u l l accord with For example,  a 1-proton ddd at 5 1.77  i n the region  6  1.91-2.08,  the  nmr  spectrum  of  (327)  (J - 12, 9, 8 Hz), a 4-proton multiplet  a  3-proton  multiplet  in  the  region  6  C0 Me 2  2.12-2.33,  a 1-proton dd at 6* 2.41  (J - 12, 6 Hz), a 1-proton multiplet  i n the region S 2.40-2.50, a 1-proton doublet at 6 2.98 1-proton  multiplet  3.31 and  a  resolution (327)  is  in  1-proton mass  broad  spectrometry  1 3  1 6  singlet  at  verified  6 that  5.33.  Furthermore,  the molecular formula of  diene  (327)  is  considering the s t r a i n inherent i n the molecule.  u t i l i z i n g a sequence of steps analogous to those described above  derived  Thus, when a THF solution of the  enolate  from the treatment of methyl 2-trimethylstannyl-1-cyclo-  hexenecarboxylate  (206) with LDA, was successively  treated with HMPA and  a l k y l a t i n g agent (325) at -20°C for 30 min, the corresponding ester  (328) was i s o l a t e d i n 66% y i e l d after appropriate workup. an  high  2  the diene (329) was prepared.  the  a  C H 0 .  noteworthy  anion  Hz),  the region 6 3.00-3.11, a 3-proton s i n g l e t at 6  It should be pointed out that the formation of the  By  (J - 16  CH3CN  Treatment  of  s o l u t i o n of (328) with a solution of triphenylphosphine, t r i -  ethylamine and palladium(II) acetate i n CH3CN for 21 h at 80°C, afforded the  diene  (329)  in  70% y i e l d after appropriate workup (equation 78).  The s p e c t r a l data derived from compounds (328) and (329) were  found  to  - 162 -  C0 Me  Me0 C  2  2  Pd(0) (78)  CHjCN SnMe  3  329  328  be i n f u l l accord with the assigned structures. S i m i l a r l y , when a THF solution of the enolate anion derived from the treatment  of  methyl 2-trimethylstannyl-l-cycloheptenecarboxylate  (207)  (79)  331  330 with LDA, was successively treated with HMPA and (325)  the  agent  at -48°C for 45 min, the corresponding ester (330) was i s o l a t e d i n  56% y i e l d after appropriate workup. (330)  with  a  Treatment of an CH3CN  yield  after  appropriate  derived from compounds (330) with the assigned structures. showed a 9-proton s i n g l e t at multiplet  solution  workup (equation 79).  diene  (331)  and (331) were found to be i n  full  accord  For example, the ^H nmr spectrum of S  0.15  (^J.Sn-H  ~  ^4  in  The spectral data  Hz),  a  (330)  1-proton  i n the region 6 1.22-1.35, a 2-proton multiplet i n the region  S 1.48-1.57, a 2-proton multiplet i n the region 6* 1.64-1.72, a quintet  of  s o l u t i o n of triphenylphosphine, triethylamine and p a l l a -  dium(II) acetate i n CH3CN for 4 h at 85°C afforded the 80%  alkylating  at  6  1.89  2-proton  (J = 7.5 Hz), a 5-proton multiplet i n the region 6*  2.02-2.23, a 1-proton doublet  at  6  2.43  (J  -  14  Hz),  a  2-proton  - 163 multiplet  in  the region 6 2.59-2.68, a 1-proton doublet at 5 2.81  (J =  14 Hz), a 3-proton s i n g l e t at 6 3.68 and a 1-proton t r i p l e t at 6 6.00 (J -  3.5 Hz,  isn-H  =  7  4  Hz).  In addition, high resolution mass spectro-  metry v e r i f i e d that the molecular formula of (330) A possible pathway for coupling  reaction  of  the  intramolecular  vinylstannanes-vinyl  i s Cigh^o^ISn.  Pd(O)-catalyzed  iodides  represented by the c a t a l y t i c cycle shown i n Scheme 28.  t> Scheme 28 c  can  be  envisaged  to the PdL species  2  to  could  would  The  bromides) first  is  step  XSnMe  3  oxidative addition of the carbon-halide bond  c a t a l y s t to afford an intermediate represented by [A].  This  then undergo t r a n s / c i s isomerization to afford an i n t e r -  mediate depicted by [B]. dium  be  (or  cross-  result  Transmetalation of the vinylstannane by p a l l a -  i n the formation of trimethylstannyl halide and the  - 164 -  palladium  complex  [C].  This  latter  s p e c i e s c o u l d undergo r e d u c t i v e  e l i m i n a t i o n t o a f f o r d the diene p r o d u c t PdL .  The p a l l a d i u m c a t a l y s t P d L  2  2  [D] and the  palladium  catalyst  c o u l d then undergo another  catalytic  cycle. I n c o n c l u s i o n , i t i s c l e a r t h a t many m o d i f i c a t i o n s and e x t e n s i o n s t o the  intramolecular  Pd(0)-catalyzed  above c a n be e n v i s a g e d . of  bicyclic^  2  triene  thus i l l u s t r a t i n g natural  product  cross-coupling reactions described  However, i t i s a l r e a d y apparent t h a t a and t r i c y c l i c diene  the p o s s i b i l i t y synthesis.  systems have been  o f applying  In p a r t i c u l a r ,  natural  VI.  ( e . g . (327))  a r e examples  prepared,  methodology t o  i t s h o u l d be n o t e d t h a t the  syntheses o f f u n c t i o n a l i z e d bicyclo[5.3.0]decadienes triquinanes  this  ( e . g . (316)) and  o f r i n g systems found i n many  products.  Miscellaneous  I n the e a r l y p a r t o f the d i s c u s s i o n ( s e c t i o n II.A) o f t h i s the  variety  possibility  o f an i n t r a m o l e c u l a r  r e a c t i o n between the v i n y l s t a n n a n e  Pd(0)-catalyzed  found t h a t when a s o l u t i o n o f (134) i n THF was  Br  cross-coupling  and v i n y l bromide f u n c t i o n s  pound (134) t o a f f o r d compound (143) was d i s c u s s e d  thesis,  o f com-  ( e q u a t i o n 80). I t was  treated  with  (PPl^^Pd  COjMe Pd(PPh ) 3  SnMe 134  SnMe  3  3  SnMe  4  THF  C0 Me 2  143  3  (80)  - 165 for  24  h  at  50 C, t i c analysis of the reaction mixture indicated the o  presence of numerous polar unidentified components  and  non-polar  development with 9:1  component  (Rf  -  0.40)  petroleum e t h e r - d i e t h y l ether). on  silica  gel  afforded  to  the  nmr spectrum of  protons,  be  a  showed,  singlet  at  in  8  addition  0.16  subsequently  ( J_Sn-H " 2  to 5  o  For example, the  methylene  ^z), a 3-proton  a 1-proton multiplet i n the region 8 4.71-4.73 and  multiplet  in  the  region  6  r e s o l u t i o n mass spectrometry v e r i f i e d (143)  oil  The spectral data derived from (143) were  (143)  9-proton  relatively  Column chromatography of the black  i n f u l l accord with the assigned structure.  s i n g l e t at 8 3.68, 1-proton  gel,  a product (36% y i e l d ) , which was  i d e n t i f i e d as compound (143). found  (silica  one  4.78-4.81. that  the  In  a  addition, high  molecular  formula  of  is C H 02Sn. 13  The  22  stereochemical  configuration  established by performing irradiation at 6 0.16 caused  of  the  nOe  of  difference  s i n g l e t at 8 3.68  (143)  was  unequivocally  experiments.  For  (-OMe) caused signal enhancement  (-SnMe ), while i r r a d i a t i o n of the s i n g l e t at 8 0.16 3  signal  enhancement  at  8  3.68  example,  (-OMe)  (-SnMe ) 3  and 6 4.78-4.81 (vinyl  proton). E f f o r t s were made to increase the y i e l d of (134), but these were not successful.  For example, when the above reaction was repeated i n CH CN 3  or PhH, t i c analysis of the reaction mixture indicated the polar,  unidentified  material.  (equation 80) i n THF using palladium(II)  Similarly,  sources  of  Pd(0)  presence  repeating such  as  the a  of  reaction  mixture  of  acetate, triethylamine and triphenylphosphine resulted i n  a mixture of u n i d e n t i f i e d components.  - 166 -  EXPERIMENTAL  I. General  Melting points were determined using a apparatus and are uncorrected.  Fisher-Johns  melting  B o i l i n g points were recorded as a i r - b a t h  temperatures required for bulb-to-bulb (Kugelrohr) d i s t i l l a t i o n s uncorrected.  Infrared  (ir)  spectra  carbon tetrachloride solutions, spectrophotometer spectrophotometer film.  (internal  employing  a  calibration)  Perkin-Elmer model  solutions  Models WP-80, HXS-270, or WH-400 spectrometers Carbon nuclear magnetic resonance  magnetic resonance  (  1 1 9  given  in  6  units  and  for  ^H nmr  were  (TMS) as the i n t e r n a l standard or  signal  6  7.25). ^  The  or a Varian model ( C nmr) and 1 3  multiplicity,  number  Signal  measured to  tin  of  positions  relative  the  in  to  chloroform  protons,  constants, and assignments (where possible) are indicated sis.  using  S n nmr) were recorded on deuteriochloro-  tetramethylsilane (6"  polystyrene  (^H nmr) spectra were recorded  form solutions using a Varian model XL-300 instrument. are  a  1  on deuteriochloroform solutions or hexadeuteriobenzene  nuclear  1710  or a Perkin-Elmer model 710B  c a l i b r a t e d using the 1601 cm" band of  XL-300 instrument.  and are  were obtained on l i q u i d films or  Proton nuclear magnetic resonance  Bruker  point  coupling parenthe-  For compounds containing the a l l y l i c moiety the v i n y l protons have  been assigned as H , Hg and H Q as depicted i n the structure below. A  For  - 1 6 7 -  ^ lC n m r 6 w a s m e a s u r e d r e l a t i v et o 7 7 . 0 ) ° ^ a n d  t h e  d e u t e r o ic h o lr o f o r ms i g n a l  m u l t i p l i c i t y w a s d e t e r m n ie d r f o m A P T e x p e r m i e n t s ( a t t a c  p r o t o n t e s t ) . F o r H ^ S n n m r 5 w a s m e a s u r e d r e l a t i v e t o t e t r a m n a n e  ( 5 = 0 . 0 ) ° ^ a s  i n t e r n a l s t a n d a r d .T n ih y d r o g e n c o u p n i lg c o n s t a n t s  ( J _ S . j j ) a n d t n ic a r b o n a v e r a g e  o f t h e  c o n s t a n t s (J.Sn-c)  c o u p n i lg  n  H ^ S n  a n d  H ^ S n  T i n t i n c o u p n i lg c o n s t a n t s ( J S .r i S n ) h g ih  r e s o l u t i o n  r e s o l u t i o n  r  e  r  g v ie n  e  v a u le s( u n l e s s §i  v e n a  ^ " ^ S n v a l u e s .L o w  s  s p e c t r o m e t e r s . M o e l c u a l r  m a s  o n  w e g i h t  t h eM (C -H 3 )  p e a k . I n  +  u n  d e t e r m n ia t o in s  o n  t h eM (C -H 3 )  p e a k ,  +  o t h e r w s i e )  e  c a s e s o f c o m p o u n d s c o n  t r m i e t h y g le r m y l g r o u p s , t h e m e a s u r e m e n s t w e r e b a s e d m a d e  o n  w h e l i f o r c o m p o u n d s  ^ G e  m a d e  (M+'C^HQ)  o n  ^ 0 g 2  j 7 2 Q  na n (  6  o  r  o  n  1 1 8 g j 7 4 Q na n (  a n d  4  c o n t a n in ig b o t h  t r m i e t h y g le r m y l g r o u p a n d a t r i n b u t y l s t a n n y l g r o u p ,t h e w e r e  a n  s p e c t r o m e t r y )i nc a s e s o f c o m p o u n d s w t i h t n  m a d e  a n  s t a t e d o t h e r w  m e t h y s l t a n n y l g r o u p s w e r e b a s e d o n 1 2 0 g ( xss s t a t e d w e r e  a s  m a s s p e c t r a w e r e r e c o r d e d w t i h V a a r i n M / A T C H 4 B  K r a t o s A / E l M S 5 0 m a s ( h g ih  a  a  j  6a n c  w  e  m e a s u r e m e r  e  m a d e o n  p e a k .  G a s l i q u i d c h r o m a o t g r a p h y ( g l c ) a n a y ls e s w e r e p e r o f r m e d o n P a c k a r d  m o d e s l  5 8 8 0  H e w  o r 5 8 9 0 c a p i l l a r y g a s c h r o m a o t g r a p h s u s n ig  0 2 .1 m m f u s e d s i l i c a c o u l m n s c o a t e d w t i h c r o s s l i n k e d S E 5 4 a n d w t i h a f l m e i o n i z a t i o n d e t e c t o r s . T h n i  l a y e rc h r o m a o t g r a p h y  ( t i c ) a n a y ls e s w e r e d o n e o n c o m m  a u l m n i u m b a c k e d s i l i c a g e l p l a t e s( E . M e r c k ,T y p e b a c k e d  s i l i c a g e lp l a t e s( E . M e r c k ,  T y p e 5 7 3 5 ) .  a c c o m p s i h le d w t i h u l t r a v i o l e t l i g h t , i o d i n e , a n d o /r p l a t ew t i h  % 5  5 5 5 4 )  o r  p l a s t i c  V i s u a l i z a t i o n w a s b y  s p r a y n ig  t h  a m m o u n m i m o y l b d a e t 1 0 % a q u e o u s s u l f u r i c a c i d .  - 168 tional  column  chromatography  was  done  Merck) while flash column chromatography  on 70-230 mesh s i l i c a gel (E. was  93  done  on  230-400  mesh  s i l i c a gel (E. Merck). All  compounds  that were subjected to high resolution mass spectro-  metry were homogeneous by t i c and glc analyses. Unless otherwise stated, atmosphere  of  dry  argon  a l l reactions were using  glassware  carried  that  had  out  under  an  been thoroughly  flame-dried. Cold temperatures  used  for  various  reactions  were  follows:  ice-acetone  ( - 1 0 ° C ) , 27 g CaCl /100 mL H 0 - C 0  CaCl /100  mL H 0 - C 0  (-48°C),  2  2  2  ( - 7 8 ° C ) and methanol-N  II.  2  2  chloroform-C0  2  2  obtained  as  ( - 2 0 ° C ) , 46 g  (-63°C),  acetone-C0  2  (-98°C).  2  Solvents and Reagents  Solvents procedures. ketyl.  94  and  reagents  were  purified  Ether and THF were  Triethylamine,  distilled  diisopropylamine,  and dried using from HMPA,  d i s t i l l e d from calcium hydride.  Methylene chloride  chloride  P 05.  were  distilled  from  2  Petroleum  sodium DMSO and ether  established benzophenone  and  DMF were  carbon  tetra-  refers to the  f r a c t i o n b o i l i n g between 3 0 - 6 0 ° C . Hexamethylditin bromotrimethylgermane  was  obtained  and  from  Organometallics  while  tetrakistriphenylphosphinepalladium(O)  obtained either from A l d r i c h Chemical Co. Inc. or from Inc.  Inc.,  Morton  (Alfa Products) and were used without further p u r i f i c a t i o n .  were  Thiokol,  - 169 Solutions  of methyllithium (low halide)  hexane and diisobutylaluminum  hydride  in  i n ether, n-butyllithium i n hexane  were  obtained  from  A l d r i c h Chemical C o . , Inc. and the former two reagents were standardized using the procedure of Kofron and B a c l a w s k i . ^ Cuprous bromide-dimethyl sulfide complex was prepared by the of H o u s e ,  method  after washing commercial cuprous bromide with methanol. *  9 6 a  96  Saturated  aqueous  ammonium  chloride  (pH  8)  5  was prepared by the  addition of 50 mL of aqueous ammonium hydroxide (58%) to 1  L  of  satu-  rated aqueous ammonium chloride. Lithium  diisopropylamide  (IDA)  was  prepared by the addition of a  s o l u t i o n of a l k y l l i t h i u m i n ether or hexane to a solution of diisopropylamine  (1 equiv)  i n dry THF at - 7 8 ° C .  The r e s u l t i n g c o l o r l e s s  solution  was then s t i r r e d at 0°C for 10 min before being used.  Preparation of Q,^-acetylenic  III.  General Procedure 1:  esters  Preparation of a . B - a c e t y l e n i c esters  R—=====—C0 R' 2  To a cold ( - 7 8 ° C ) ,  s t i r r e d solution of the appropriate  equiv)  in  ether.  The r e s u l t i n g solution was  warmed  to  1-alkyne  (1  dry THF was added a solution of methyllithium (1.2 equiv)  -20°C  and  stirred  stirred  at  -78°C  for  10-15  at t h i s temperature for 1 h.  ethyl chloroformate (1.5 equiv) was added and the s o l u t i o n  was  in  min,  Methyl or stirred  - 170 at  -20°C  for  1  h and at room temperature for 1 h.  sodium bicarbonate and ether were added. ated,  washed  with  dried over anhydrous  saturated magnesium  Saturated aqueous  The organic layer  separ-  aqueous sodium bicarbonate and brine and sulfate.  Concentration,  p u r i f i c a t i o n (column chromatography and/or d i s t i l l a t i o n ) oil  was  followed  by  of the residual  afforded the appropriate ester.  Preparation of 6-bromo-l-hexanol (92)  To a s t i r r e d solution of 1,6-hexanediol 100  mL of  bromide. the  dry benzene  (91) (5.0 g, 42.3  mmol)  was added 6.76 mL (84.6 mmol) of 48% hydrogen  A Dean Stark water trap was attached to the reaction flask and  mixture  was refluxed for 23 h.  The solution was washed with 50 mL  of 6 M sodium hydroxide, 50 mL of 10% hydrochloric acid and 100 brine and then was dried over anhydrous magnesium s u l f a t e . of the s o l u t i o n showed that i t contained the monobromide corresponding dibromide.  mL of  Glc analysis (92)  and the  Concentration, followed by column chromatogra-  phy of the r e s i d u a l o i l on s i l i c a gel petroleum  (20  g,  elution  initially  (70%)  of  the bromide (92). 1  X  3  1.59  (quintet,  5.834  This colorless o i l exhibited i r (film):  3300 ( b r ) , 1450, 1060 c m ' ; H nmr (270 MHz, CDC1 ) 3H),  with  ether and then with d i e t h y l ether) and d i s t i l l a t i o n (air-bath  temperature 5 8 - 6 0 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded g  in  2H, J - 7 Hz), 1.89 (quintet,  6:  1.33-1.52  (m,  2H, B r C H C H - , J = 7 2  2  - 171 Hz),  3.42  (t,  2H, B r C H - , J = 7 Hz), 3.65  (t,  2  Exact Mass c a l c d . for C H 6  8 1 n  Br  Preparation of 6-bromohexanal  (M+^O):  2H, -CH OH,  J  2  164.0025;  -  found:  7  Hz).  164.0021.  (93)  H  Br O To  a  stirred  solution  of pyridinium chlorochromate (6.1 g, 28.30  mmol) and sodium acetate (0.58 g, 7.07 mmol) i n 25 mL of methane  was  added a solution of 6-bromo-l-hexanol (92)  mmol) i n 55 mL of dry dichloromethane. for  The brown  dry  dichloro-  (2.576 g,  mixture  was  14.15  stirred  1.5 h at room temperature and then was poured into 300 mL of d i e t h y l  ether.  The mixture was passed through a short column of F l o r i s i l  elution  with  diethyl  ether).  Concentration  (20 g,  of the combined eluate,  followed by d i s t i l l a t i o n (air-bath temperature 5 5 - 6 0 ° C / 0 . 0 5 Torr) of the residual  oil,  afforded  1.76  g  (69%)  of  the  aldehyde  c o l o r l e s s o i l exhibited i r (film): 2700, 1708,  1450,  (270  1.58-1.72  MHz,  CDC1 ) 3  6:  1.39-1.55  (quintet, 2H, J - 7 Hz), 2.40 2H, for  -CH Br, J - 7 Hz), 9.75 2  C H 6  7 9 1 0  Br  (m,  2H),  (93).  1280 cm" ; 1  This  ^-H nmr  (m,  2H),  1.87  (td, 2H, -CH CH0, J - 7, 1 Hz),  3.49  (t,  2  (t,  (M+-1): 176.9916;  IH, -CHO, J - 1 Hz). found: 176.9919.  Exact Mass c a l c d .  - 172 Preparation of 1.1.7-tribromo-l-heptene  (94)  Br Br  Br  To a s t i r r e d solution-suspension mmol)  in  100  of triphenylphosphine (5.13 g, 19.5  mL of dry dichloromethane was added carbon tetrabromide  (19.5 mmol) and zinc dust (19.5 mmol). been  After the reaction  mixture  had  s t i r r e d at room temperature for 23 h, a solution of 6-bromohexanal  (93) (1.76 g, 9.77 mmol) i n 20  mL of  dropwise over a period of 20 min.  the  supernatant  solution  dichloromethane  was  added  The r e s u l t i n g burgandy suspension was  s t i r r e d at room temperature for 2 h. and  dry  Petroleum ether (350 mL) was added  was decanted from the o i l .  The o i l was  taken up i n 70 mL of dichloromethane, petroleum ether (350 mL) was added and  the  combined  supernatant solution was again decanted. supernatant  solutions,  followed  by  Concentration of the  distillation  (air-bath  temperature 8 0 ° C / 0 . 0 5 Torr) of the residual o i l afforded 3.15 g (96%) of the tribromide (94). 1450, (m,  800 cm - ; -  1  X  This colorless  oil  exhibited  H nmr (270 MHz, CDC1 ) 6:  ir  (film):  1620,  1.41-1.56 (m, 4H), 1.81-1.95  3  2H), 2.08-2.19 (m, 2H), 3.41 (t, 2H, -CH Br, J = 7 Hz), 6.40 (t, IH,  vinyl  2  proton,  337.8354;  J  found:  7  Hz).  Exact  Mass  c a l c d . for C H 7  337.8354.  Preparation of methyl 8-bromo-2-octvnoate  (95)  C0 Me 2  8 1 1 1  Br  3  (M+) :  - 173 To a cold ( - 7 8 ° C ) , (3.15  g,  9.319  s t i r r e d solution of 1,1,7-tribromo-l-heptene  mmol)  in  120  mL of dry THF was added a solution of  n-butyllithium (23.29 mmol) i n hexane. for  1  The mixture was s t i r r e d at -78°C  h and at room temperature for 1 h.  The solution was then cooled  to - 2 0 ° C , methyl chloroformate (10.25 mmol) was added, and the was  stirred  at  90°C/0.05  of the ester (95). 1430,  1310-1200  (m, 4H), 1.89 -CH f>C-C0 Me, 2  2  -OMe).  solution  -20°C for 1 h and at room temperature for 1 h.  as described i n general procedure 1 followed by temperature  distillation  Workup  (air-bath  Torr) of the residual o i l , afforded 1.95 g (89%)  This colorless o i l exhibited i r (film): 2200, (br), 1078 cm" ; H nmr (270 MHz, 1  (quintet, J  (94)  2H,  X  BrCH CH -, 2  = 7 Hz), 3.41  (t,  2  J  -  7  Hz),  6:  1.54-1.68  2.38  (t,  2H, B r C H - , J - 7 Hz), 3.77 2  Exact Mass c a l c d . for C H O B r (M+-0CH3): 8 1  8  C D C I 3 )  1 0  1700,  202.9896;  2H,  (s, 3H, found:  202.9896.  Preparation of 6-chlorohexanal  (96)  H  Cl O To  a  stirred  solution  of  pyridinium chlorochromate (7.5 g,  mmol) and sodium acetate (0.71 g, 8.7 mmol) i n 25 mL of methane  was  dichloro-  added a solution of 6-chloro-l-hexanol (2.37 g, 17.4 mmol)  i n 35 mL of dry dichloromethane. h  dry  34.8  The brown mixture was s t i r r e d for  1.45  at room temperature and then was poured into 300 mL of d i e t h y l ether.  The mixture was passed through a short column of F l o r i s i l  (20 g,  elution  - 174 -  with  d i e t h y l ether).  Concentration of the combined eluate, followed by  d i s t i l l a t i o n (air-bath temperature 6 0 - 6 5 ° C / 0 . 0 5 Torr) oil,  afforded  1.83  g  (79%) of the aldehyde (96).  exhibited i r (film): 2700, 1708, CDC1 )  6:  3  1.41-1.59  (m,  C1CH CH -, J - 7 Hz), 2.52 2  2  -CH C1,  J - 7 Hz), 9.80  2  C H 0 C1 3 5  6  1 1  (M+-1):  1455,  2H),  1300  cm" ; 1  of  the  residual  This colorless *H nmr  1.60-1.75 (m, 2H), 1.82  (300 MHz,  (quintet, 2H,  (td, 2H, -CH CH0, J - 7, 1 Hz), 3.66  (t,  133.0420;  2  IH, -CHO, J - 1 Hz). found:  oil  (t,  2H,  Exact Mass c a l c d . for  133.0419.  Preparation of 1.l-dibromo-7-chloro-l-heptene  (97)  Br  To a s t i r r e d solution-suspension of triphenylphosphine (7.16 mmol) (9.05  in  120  had  been  6-chlorohexanal (96) was  added  stirred  dust  (27.3  mmol).  was  Petroleum  ether  (400  and the supernatant s o l u t i o n was decanted from the o i l . ether  was added and the supernatant solution was again decanted.  t r a t i o n of the combined supernatant solutions, (air-bath  reaction  The r e s u l t i n g tan suspen-  The o i l was taken up i n 70 mL of dichloromethane, petroleum mL)  the  (1.83 g, 13.6 mmol) i n 25 mL of dry dichloromethane  dropwise over a period of 20 min.  added  After  at room temperature for 24 h, a solution of  sion was s t i r r e d at room temperature for 2.5 h. mL)  27.3  mL of dry dichloromethane was added carbon tetrabromide  g, 27.3 mmol) and zinc  mixture  g,  followed by  (300  Concen-  distillation  temperature 7 0 ° C / 0 . 0 5 Torr) of the residual o i l afforded 3.71  - 175 g (94%) of the dibromoolefin (97). (film):  1610,  1440,  1210,  This  800  colorless  cm" ; 1  1  H  nmr  oil  (300  exhibited  MHz,  1.38-1.56 (m, 4H), 1.73-1.86 (m, 2H), 1.97-2.10 (m, 2H), -CH C1,  J - 7 Hz), 3.75  2  Hz).  (s,  3H, -OMe), 6.40  Exact Mass c a l c d . for C H 7  7 9 1 1  Br  8 1  Br  3 5  (t,  Cl  ir  CDC1 ) 6: 3  3.53  (t,  2H,  IH, v i n y l proton, J - 7  (M+) :  289.8897;  found:  289.8896.  Preparation of methyl 8-chloro-2-octvnoate  To  a  cold  heptene (97) solution  (-78°C),  (3.71  stirred  solution  g, 12.8 mmol) i n 120  of  mL of  1,l-dibromo-7-chloro-ldry  of n-butyllithium (28.1 mmol) i n hexane.  was s t i r r e d at -78 C for 1 h and at  room  C  solution  (98)  THF was  temperature  for  1  h.  stirred  at  temperature  -20°C  for  for  1  1  h.  The  (13.0 mmol) was h  and  at  room  Workup, as i n general procedure 1, followed by  d i s t i l l a t i o n (air-bath temperature 9 5 ° C / 0 . 0 5 Torr) of the residual afforded ir  (film):  2.131  g (89%) of the ester (98).  2220, 1445,  (m, 4H), 1.80  This colorless o i l  1080 cm" ; H nmr (270 MHz, CDCI3) 6: 1  X  (quintet, 2H, C1CH CH -, J - 7 Hz), 2.37  J - 7 Hz), 3.53  2  (t,  2  2H, -CH C1, J - 7 Hz), 3.77 2  Mass c a l c d . for C H O C l (M+-0CH3): 157.0416; 3 5  g  1 0  a  The reaction mixture  was then cooled to - 2 0 ° C , methyl chloroformate  added and the solution was  added  (s,  (t,  3H,  157.0418.  oil,  exhibited 1.55-1.67  2H, - C H O C - , 2  -OMe).  Exact  - 176 Preparation of methyl 8-iodo-2-octvnoate  (99)  ^=—C0 Me 2  To  a  stirred  solution of methyl 8-bromo-2-octynoate  (95)  4.132 mmol) i n 40 mL of acetone was added sodium iodide (2.48 mmol).  The s o l u t i o n was s t i r r e d at reflux for 7.5 h.  residue,  then  was  g,  16.53  The s o l u t i o n was  concentrated, petroleum ether (40 mL) and water (20 mL) the  (967 mg,  were  added  to  the organic layer was washed twice with water (15 mL) and  dried  over  anhydrous  magnesium  sulfate.  Concentration,  followed by d i s t i l l a t i o n (air-bath temperature 8 0 - 8 5 ° C / 0 . 0 5 Torr) of the r e s i d u a l o i l afforded 1.08 g (93%) of the iodide (99). oil  exhibited i r (film): 2236, 1714,  8:  1.50-1.70 (m, 4H), 1.88  (quintet,  (t,  2H, -CH C=C-, J - 7.5 Hz), 3.22 2  3H, -OMe).  Exact Mass  calcd.  1256 c m ; - 1  colorless  H nmr (300 MHz, CDC1 ) 3  2H, I C H C H - , J 2  (t,  for  X  This  2  7.5  Hz),  2.49  2H, I C H - , J - 7.5 Hz), 3.80 2  C H 0 I 9  1 3  2  (M+) :  279.9962;  (s,  found:  279.9965.  Preparation of methyl 6-chloro-2-hexynoate  (100)  Cl Following  general  of 5-chloro-l-pentyne a  solution  of  procedure 1, to a cold ( - 7 8 ° C ) , s t i r r e d solution (3.3 g, 3.24 mmol) i n 120 mL of dry THF was  methyllithium  (4.12  mmol)  i n ether.  added  The mixture was  - 177 s t i r r e d at -78°C for 15 min and at -20°C for 1 h. (4.54 for  temperature  Normal  workup,  115-118°C/12  1700,  1250  (br);  X  H  2  of  nmr  (270  2  C H 0 C 1 (M+): 160.0291; 9  2  distillation  (air-bath  residual o i l afforded 4.654 g  3  6:  2.05  (quintet, 2H,  2H, C1CH CH CH -, J - 7 Hz), 3.65 2  C1CH CH CH -, J - 7 Hz), 3.78 2  the  MHz, CDC1 )  (t,  2  2  by  This colorless o i l exhibited i r (film): 2230,  C1CH CH CH -, J - 7 Hz), 2.55 2  followed  Torr)  (90%) of the ester (100).  7  chloroformate  mmol) was added and the solution was s t i r r e d at -20°C for 1 h and  1 h at 0 ° C .  2H,  Methyl  (s,  2  3H, -OMe).  2  (t,  Exact Mass c a l c d . for  found: 160.0291.  Preparation of methyl-6-bromo-2-hexynoate  /s.  ^  (101)  =====—C0 Me 2  Br To a mixture of a solution of methyl 6-chloro-2-hexynoate mg,  (510  2.712 mmol) i n 1.5 mL of heptane and 1.5 mL of H 0 was added sodium 2  bromide (1.39 g, 13.5 mmol) and Adogen 464® (-4 drops). s t i r r e d at 100°C for 4.5 h.  aqueous  layer  was  The mixture was  Glc analysis of the organic layer indicated  the presence of 54% of the chloride (100) The  (100)  removed  and  and 39% of the bromide  (101).  1.5 mL of H 0 , sodium bromide (5 2  equiv) and Adogen 464® (-4 drops) were added to The mixture was s t i r r e d at 100°C for 5 h.  the  organic  solution.  Removal of the aqueous layer,  addition of fresh H 0-NaBr-Adogen 464®, and subsequent refluxing for 5 h 2  was  repeated two more times.  Glc analysis of the organic layer at this  stage indicated the presence of 93% of  the  bromide  (101).  Petroleum  - 178 ether (20 mL) was added, the organic three  was  separated  and  washed  times with saturated aqueous ammonium chloride and then was dried  over anhydrous magnesium sulfate. tion  Concentration, followed by  distilla-  (air-bath temperature 6 5 ° C / 0 . 0 5 Torr) of the residual o i l afforded  402 mg (72%) of the bromide (101). (film): 2.11 7  layer  2238,  (quintet,  Hz), 3.50  1713,  This  colorless  1251 (br), 1079 c m ; - 1  X  (t,  2H, BrCH CH CH -, J 2  2H, BrCH CH CH -, J - 7 Hz), 3.77  Mass c a l c d . for C H 0 7  9  8 1 2  2  2  B r (M+):  205.9766;  Preparation of methyl 6-iodo-2-hexvnoate  (s,  found:  mmol)  mmol).  in  2  Exact  (102)  (780  mg,  20 mL of acetone was added sodium iodide (2.95 g,  19.5  petroleum  ether  (100)  The  solution  was  dried  over  anhydrous  magnesium  sulfate.  Torr)  residual  This  o i l afforded 1.12 g (91%) of the iodide (102).  o i l exhibited i r ( f i l m ) : 2240, 1713, 6:  2.04  (quintet,  I C H C H C H - , J - 7 Hz), 3.27 2  2  2  2H, (t,  1262,  1078 cm" ; H nmr 1  I-  ICH CH CH -, 2  2  2  X  7  2  2  of  Hz),  the  colorless (270 MHz,  Hz), 2.47  2H, ICH CH CH -, J - 7 2  and  Concentration,  followed by d i s t i l l a t i o n (air-bath temperature 70"C/0.05  CDCI3)  was  (30 mL) and water (20 mL) were added to  the residue, the organic layer was washed twice with water (15 mL), then  -  205.9767.  The solution was s t i r r e d at reflux for 16 h.  concentrated,  2  3H, -OMe).  To a s t i r r e d solution of methyl 6-chloro-2-hexynoate 4.875  ir  H nmr (270 MHz, CDC1 ) 6:  (t,  2  2  exhibited 3  2H, B r C H C H - , J - 7 Hz), 2.56 2  oil  (t, 2H,  3.74  (s,  - 179 3H,  -OMe).  Exact  Mass  calcd.  for  C H 0 I 7  9  2  (M+):  251.9649;  found:  251.9646.  Preparation of ethvl 5-p-toluenesulfonvloxy-2-pentvnoate  (103)  C0 Et 2  To a s t i r r e d solution of ethyl 5-hydroxy-2-pentynoate mmol) i n 25 mL of dry CH2CI2 was added g,  6.340  30  p_-toluenesulfonylchloride (1.21  mmol), pyridine (0.69 mL, 8.53 mmol) and 4-dimethylaminopyri-  dine (0.5 g, 4.1 mmol). for  (563 mg, 4.26  h.  The solution was s t i r r e d  at  room  temperature  The solution was concentrated, petroleum ether (50 mL) was  added to the residue and  the  organic  solution  was  washed  with 10%  hydrochloric acid (20 mL), saturated aqueous sodium bicarbonate (20 mL), water (20 mL) and then Concentration, oil  was  followed  dried  and  with  colorless  oil  2.50  (s,  petroleum  ether-ethyl  X  3H, Jfe),  of  the  p."  t o l u e n e s u  exhibited i r (film): 2247, 1713,  1080 cm" ; H nmr (80 MHz, CDCI3) 6: 1  magnesium  sulfate.  acetate;  d i s t i l l a t i o n (air-bath temperature 80°C/0.05 Torr) of the o i l  thus obtained afforded 600 mg (47%) This  anhydrous  by flash column chromatography of the r e s i d u a l  on s i l i c a gel (20 g, e l u t i o n  1:1)  over  2.75  (t,  1.32 (t,  lf°  1365,  n a t e  1260,  (103). 1177,  3H, -OCH CH , J -=• 7 Hz), 2  3  2H, -CH CH OTs, J - 7 Hz), 4.17 (t, 2H, 2  2  -CH CH OTs, J - 7 Hz), 4.22 (q, 2H, -OCH CH , J - 7 Hz), 7.37 (d, 2H, J 2  2  2  3  We thank Mr. John Wai for a sample of this compound.  - 180 -  8  Hz),  7.72  (M+): 296.0718;  (d,  2H,  J  - 8 Hz).  Exact Mass c a l c d . for C H 0 S 1 4  (104)  To a s t i r r e d solution of the ester (103)  was s t i r r e d at room temperature for 3 days. (20  mL)  The solution  Water (10 mL) and petroleum  The combined organic extracts were  anhydrous magnesium sulfate.  mg  (film): 3H, 2H,  (90%) 2241,  of  1256,  bromide (104).  This colorless  afforded  o i l exhibited i r 1.30  (t,  -OCH CH , J - 7 Hz), 2.75-3.02 (m, 2H), 3.30-3.57 (m, 2H), 4.20  (q,  2  1713,  the  dried  Concentration, followed by d i s t i l l a -  t i o n (air-bath temperature 8 0 ° C / 0 . 0 5 Torr) of the residual o i l 365  10  were added and the aqueous layer was washed three times  with petroleum ether (15 mL). over  (570 mg, 1.926 mmol) i n  of dry DMF was added sodium bromide (0.6 g, 7.7 mmol).  ether  5  found: 296.0714.  Preparation of ethyl 5-bromo-2-pentynoate  mL  1 6  1075 cm" ; H nmr (80 MHz, CDC1 ) 6:  158.9446;  X  3  3  -OCH CH , J - 7 Hz). 2  1  3  found: 158.9443.  Exact  Mass  calcd.  C H 0 Br 8 1  5  4  (M -0CH CH ): +  2  3  - 181 Preparation of methyl 2.8-nonadlvnoate 2.8-decadivndioate  (106)  and dimethyl  (107)  H Me0 C  C0 Me 2  Me0 C  2  2  106 Following  107  general  procedure 1, to a cold ( - 7 8 ° C ) ,  of commercially available 1,7-octadiyne (105) 70  s t i r r e d solution  (2.542 g, 23.98  mmol)  in  mL of dry THF was added a solution of methyllithium (31.17 mmol) i n  ether.  After the reaction mixture had been s t i r r e d at -78°C for 10  min  and at -20°C for 1 h, methyl chloroformate (33.5 mmol) was added and the s o l u t i o n was s t i r r e d at -20°C for 1 h and at room temperature for Normal  afforded  two  oils  with  A and B.  petroleum  colorless  oil.  cm" ; 1  X  g (40%) of the monoester  g (32%) of the diester  for  H nmr (300 MHz, CDC1 ) 6: 3  (dt,  2H, Me0 CC«CCH -, J - 7 Hz), 3.76 2  C  1 0  2  H 0 2 (M+-1): n  Compound (107) 2245, 1733,  1456,  (107)  2:3)  (106)  as  a  as a white s o l i d .  exhibited i r (film): 3296, 2238,  acetylenic proton, J - 2 Hz), 2.23 (t,  ether;  D i s t i l l a t i o n (air-bath temperature 1 6 0 ° C / 0 . 0 5 Torr) of  B afforded 1.709 Compound (106)  ether-diethyl  D i s t i l l a t i o n (air-bath temperature 1 0 0 ° C /  0.05 Torr) of o i l A afforded 1.573  1080  h.  workup, followed by column chromatography of the residual o i l on  s i l i c a gel (100 g, e l u t i o n  oil  1  163.0759;  found:  1718,  1436,  1.60-1.81 (m, 4H), 1.98 2  (s,  3H, -OMe).  Exact Mass c a l c d .  163.0757. 2  1084cm- ;  (m, 4H), 2.32-2.48 (m, 4H), 3.78  1  X  (s,  (t, IH,  2H, HC=CCH -, J - 7, 2 Hz), 2.39  exhibited; m.p. 34°C (from methanol-H 0); i r 1279,  1260,  H nmr (300 MHz, 3H, -OMe).  CDCI3)  5:  Exact Mass  (CC1 ): 4  1.68-1.80 calcd.  for  - 182 -  C  11 11°3  (M+-0CH3): 191.0708;  H  found: 191.0714.  Preparation of methyl 8-bromonon-8-en-2-ynoate  (108)  Br  C0 Me 2  To a cold ( 0 ° C ) , s t i r r e d solution nonane  (4.02  mL,  4.02  of  B-bromo-9-borabicyclo[3.3.1]-  mmol) i n 5 mL of dry dichloromethane was added  dropwise, over a period of 10 min, a solution of methyl (106)  (300  mg,  1.83  2,8-nonadiynoate  mmol) i n 5 mL of dry dichloromethane.  reaction mixture had been s t i r r e d at 0°C for 3 h, 1 mL of was  added.  2  acetic  acid  The solution was s t i r r e d at 0°C for a further 1 h and then  aqueous sodium hydroxide (3 M, 12 (30%,  After the  mL)  and  aqueous  hydrogen  peroxide  mL) were added and the mixture was s t i r r e d at room temperature  for  30 min.  The mixture was extracted three times with petroleum  (20  mL).  The combined extracts were successively washed with water  mL),  saturated aqueous sodium bicarbonate (15 mL) and water (15 mL)  then  were  dried  over  anhydrous  magnesium  sulfate.  ether  elution  (air-bath afforded  with  petroleum  temperature 388  mg  ether-diethyl ether; 4:1)  130°C/0.05  3  2H, J - 7 Hz), 3.76  of  the  (87%) of the v i n y l bromide (108).  exhibited i r ( f i l m ) : 2238, 1718, (270 MHz, CDC1 ) 6:  Torr)  1631,  1435,  1.54-1.72 (m, 4H), 2.36 (s,  3H,-0Me), 5.41  1261, (t,  oil  (15  and d i s t i l l a t i o n thus  obtained,  This colorless 1079  and  Concentration,  followed by column chromatography of the residual o i l on s i l i c a gel g,  (15  cm- ; 1  X  H nmr  2H, J = 7 Hz), 2.44  (d, IH, J = 1.5 Hz), 5.58  oil  (t,  (d, IH,  - 183 -  J -  1.5 Hz).  Exact Mass  calcd.  for  C9H  (M -OCH ):  o 8 l B r  214.9896;  +  1 0  3  found: 214.9894.  Preparation of methyl 2.6-heptadlvnoate (109) 2.6-octadivndioate  H  and dimethyl  (110)  — -  M e 0  2  C — =  v.  1 09 Following  general  procedure 1, to a cold ( - 7 8 ° C ) ,  s t i r r e d solution  of 1,5-hexadiyne (1.718 g, 22 mmol) i n 120 mL of dry  THF was  added  solution  After the  reaction  of  methyllithium  (28.6  mmol)  i n ether.  mixture had been s t i r r e d at -78°C for 15 min methyl  chloroformate  at  room  temperature  for  1  h.  B.  Distillation  afforded 1.073 Distillation 1.707  (air-bath  g (36%) of (air-bath  the  1  Compound  (109)  (br),  Normal  workup,  temperature  exhibited  1078  cm' ; 1  ir l  H  3H,  -OMe).  (90  afforded two o i l s , A  (109)  as  a  colorless  oil.  1 1 5 ° C / 0 . 0 5 Torr) of o i l B afforded  as a white s o l i d . (film):  3295,  2333,  nmr (300 MHz, CDC1 ) 6: 3  1713,  1435,  2.08  (t, IH,  acetylenic proton, J - 2 Hz), 2.44-2.52 (m, 2H), 2.55-2.62 (m, 2H), (s,  h,  temperature 9 0 - 9 3 ° C / 2 0 Torr) of o i l A  monoester  g (40%) of the diester (110)  1338-1100  for  by column chromatography of the residual o i l on s i l i c a gel  g, e l u t i o n with petroleum ether-diethyl ether; 2:3) and  -20°C  (30.8 mmol) was added and the solution was s t i r r e d  at -20°C for 1 h and at followed  and  a  Exact Mass c a l c d . for C H 0 8  7  2  (M+-1):  3.78  135.0446; found:  - 184 135.0448. Compound (110) (CC1 ): 4  2237,  exhibited,  1733,  CDCI3) 8: 2.64  (s,  Mass c a l c d . for C  1435,  m.p.  63-64°C  (from  H  1 0  0  4  2  1  (M+) :  194.0579;  Preparation of methyl 6-hepten-2-ynoate  (s,  found:  X  6H,  -OMe).  194.0574.  (109)  (1.065 g, 7.83 mmol) i n  50 mL of hexane was added 10% palladium-on-barium sulfate reaction  been consumed.  ether;  17:1)  and  g,  elution  distillation  1258, (s,  921 c m ' ; 1  3H,  -OMe),  X  H nmr (300 MHz, CDCI3) 6: 5.06  mg  After  material  petroleum  (73%) of  2.28-2.48  (dd, IH, Hg, J - 10, 2 Hz), 5.10  (ddt, IH, H , J = 17, 10, 6 Hz).  C H 0 (M+-OCH3): 107.0497; 7  with  This colorless o i l exhibited i r (film): 3081,  17, 2 Hz), 5.83 7  starting  and  ether-  (air-bath temperature 9 0 ° C / 2 0  Torr) of the o i l thus obtained, afforded 789 (111).  mg)  Concentration, followed by column chromatography of  the r e s i d u a l o i l on s i l i c a gel (20 diethyl  (106  vessel was connected to a hydrogenation apparatus.  2.15 h glc analysis of an aliquot indicated that the had  Exact  (111)  To a s t i r r e d solution of the monoester  the  ir  1300-1200 (br), 1077 cm" ; H nmr (300 MHz,  4H, methylene protons), 3.79 1 0  H 0-methanol);  c  found: 107.0504.  the  alkene  2332, 1718, (m,  1643,  4H), 3.73  (dd, IH, H , J =  Exact Mass c a l c d .  A  for  - 185  -  Preparation of d i e t h y l 2.7-nonadiyndioate  Et0 C  ^=  2  Following of  general  1,6-heptadiyne  solution  of  procedure 1,  to a c o l d ( - 7 8 ° C ) ,  (928 mg, 10 mmol) i n 60 mL o f  methyllithium  m i x t u r e had been s t i r r e d a t ethyl  (112)  chloroformate  (14  mmol)  in  dry  ether.  - 7 8 ° C f o r 10 min and a t  stirred  solution  THF was  added  A f t e r the  reaction  -20°C  for  40  a  min,  (15 mmol) was added and the s o l u t i o n was s t i r r e d a t  - 2 0 ° C f o r 30 min and a t room temperature  for  30  min.  Normal  workup,  f o l l o w e d by column chromatography o f the r e s i d u a l o i l on s i l i c a g e l ( 1 0 0 g,  e l u t i o n with petroleum e t h e r - d i e t h y l  and B .  D i s t i l l a t i o n ( a i r - b a t h temperature  a f f o r d e d 1.28 bited 1.32 -  ir  7.5  (film):  Hz),  -OCH CH , 3  179.0708; 1  g (57%)  2239,  1713,  2.5  (t,  J «=• 7 H z ) . found:  Exact  179.0714.  This  1251-1173 ( b r ) ;  4 H , methylene Mass  1:1)  X  colorless  oil  exhi-  protons, for  3  2 H , methylene J = 7.5 C  H 1 2  protons,  H z ) , 4.22  16°4  A  of o i l A  H nmr (400 MHz, C D C 1 )  (quintet,  calcd.  a f f o r d e d two o i l s ,  1 3 2 - 1 3 7 ° C / 0 . 0 5 Torr)  (112).  o f the d i e s t e r  6 H , OCH2CH3, J = 7 H z ) , 1.87  (t,  2  ether,  6: J  (q, 4 H ,  (M+'OC^CT^):  - 186 IV.  Synthesis of a l k y l (Z)- and (E)-2,3-bis(trimethylstannyl)-2alkenoates and (E)-N,N-dimethyl)-2,3-bis(trimethylstannyl)-2alkenamides  General  Procedure  2:  stannyl) -2-alkenoates  Preparation  (Z)-2.3-bis(trimethyl-  Me Sn  SnMe  R  C0 R'  3  2  a s t i r r e d solution of the appropriate acetylenic ester (1 equiv)  i n dry THF (-15 followed  mL per  mmol)  was  added  hexamethylditin  solution  gave  a  for  4-62  h.  Concentration  of  silica  gel  (elution  with  petroleum  on  a  The  of  short  the  path  ether-diethyl ether)  y i e l d i n g , after concentration of the appropriate f r a c t i o n s , a oil.  equiv)  brown-black o i l , which was chromatographed (to remove  r e s i d u a l hexamethylditin and insoluble material)  column  (1  by Pd(PPh3)4 (0.009-0.02 equiv) and the mixture was s t i r r e d at  room temperature or under reflux  any  alkyl  (83)  3  To  of  colorless  o i l was then subjected to a vacuum of 0.05 Torr for 1-2 h at  room temperature.  - 187 General  Procedure  Preparation  3:  stannyl) -2-alkenoates  of  alkvl  (78)  Me Sn  C0 R'  R  SnMe  3  2  3  To a one-necked, round bottomed flask added  the  (E)-2.3-bis(trimethyl-  appropriate  alkyl  containing  either  distilled  directly  Torr) or was subjected to flash  condenser  was  (Z)-2,3-bis(trimethylstannyl)-2-alkenoate  and the sample was heated to 75-95°C for 6-48 h. then  a  (receiving  yellow  oil  was  bulb cooled to - 1 0 ° C ,  gel  (elution with petroleum ether-diethyl ether) p r i o r to d i s t i l l a t i o n .  The  alkyl  chromatography  on  0.1  silica  resultant  column  The  (E)-2,3-bis(trimethylstannyl)-2-alkenoate  was  thus  obtained as a colorless o i l .  Preparation of ethvl (Z)- and (E)-2.3-bis(trimethylstannyl)-2-butenoate (124)  and (77)  Me Sn  SnMe  3  Me 124 Following butynoate (70) hexamethylditin  general  Me Sn  3  C0 Et  2  Me  2  SnMe  3  77 procedure  (344 mg, 3.07 mmol) (3.07  C0 Et  3  mmol)  and  2, in  to a s t i r r e d s o l u t i o n of ethyl-245  mL of  (PPh ) Pd 3  4  dry  THF was  (50 mg, 0.043 mmol).  added The  - 188 -  mixture was followed  stirred  by  gel (30  of  4  J  S n  (s,  9H, -SnMe.3, 1.27  - H - 10 Hz, (75.6  (t, J  3  thus  (s),  (M -CH ): 3  2  J  S  n  .  to  isomer  1200,  _  1040,  (124).  (q,  (s),  2  I  S n  1  171.7  =  (0.05 Torr; 1.5 h) colorless  (s,  9H, -SnMe.3, J_Sn-H " 2  (s,  3H, v i n y l methyl,  2  2  H  (s).  =  3  2  6  Hz  > • -°-  > -Sn-C "  z  3j  Hz);  3  7  1  Hz  8  > ,  lj  60.1  silica  gel  thus  (t) ,  n  (78 mg,  2  2  0.176  Flash column chromatography of the  2  mmol)  crude  product  (5 g, e l u t i o n with petroleum e t h e r - d i e t h y l ether;  obtained,  6:  -Sn-H ~  methyl,  lj  =  converted, after s t i r r i n g at 79°C for 30 h, into the b i s ( t r i m e t h y l -  CDCI3)  Hz);  C  Exact Mass c a l c d . for C H 3 0 S n  17:1)  afforded 64 mg (82%) of the (E) isomer (77).  c o l o r l e s s o i l exhibited i r ( f i l m ) : 1685,  2j  1 3  <1» -Sn-C  followed by d i s t i l l a t i o n (air-bath temperature 7 0 - 7 5 ° C / 0 . 1 Torr) of oil  oil  X  (q, 2H, -OCH CH , J_ - 7  6  and  found: 426.9743.  stannyl) ester (77). on  19:1)  3  (q, ^ S n - C  -C  ether;  775 cm" ; H nmr (80 MHz, CDC1 )  Following general procedure 3, the ester (124) was  Concentration,  This  3  " 4 ° Hz), 4.15  H  26.4  159.8  h.  vacuum  - 52.5 Hz), 0.25  H  2  426.9743;  +  4  ether-diethyl  obtained  CDCI3) 6: -7.2  (q),  for  3H, -OCH CH , J - 7 Hz), 2.07  S n  MHz,  342 Hz), 14.5 149.9  oil  petroleum  i r ( f i l m ) : 1702,  Hz),  nmr  with  the  temperature  1.29 g (95%) of the (Z)  exhibited 6: 0.22  room  chromatography of the r e s i d u a l brown o i l on s i l i c a  elution  subjection  53.5  column  g,  afforded,  at  1 3  5  4  0.14 4  J  Hz  S n  )>  -H  1  (s, "  2  8  9H, -SnMe.3, 3  H  2  2  1  1  3  3  9  Hz), 14.3  -H "  S n  5  775 c m ; - 1  3  Hz, I n - H " 3  4  Hz), 4.17  9  (q), 28.2  (q,  -6.7 2  J  S  .  C  (s,  9H, -SnMe.3, 3H,  vinyl  (q, 2H, -OCH CH , J - 7  (q, ^ s n - C " n  This  H nmr (80 MHz,  (s,  3  S  1  Hz), 0.25  . -OCH CH , J - 7 Hz), 2.22  C nmr (75.6 MHz, CDCI3) 6:  -Sn-C -  J  1230,  the  = 62 Hz -  2  3  3  4  J  4  S n  Hz  3  >> " -  . ). C  5  60.8  9  (l. (t),  - 189 -  144.2  (s),  171.6  (M+-CH3):  (s),  426.9743;  180.9  found:  (s).  Exact Mass c a l c d . for C H 2 3 0 S n 11  2  2  426.9740.  Preparation of methyl (Z)- and (E)-2 .3-bis (trimethylstannyl')-2pentenoate (125)  and (147)  Me Sn 3  Et  SnMe  H  3  Me Sn  C0 Me  Et  2  125  C0 Me  H  3  147  2  SnMe  Following general procedure 2, to a s t i r r e d solution pentynoate  (114)  hexamethylditin mixture  was  (1.13  g,  9.94  3  at  room  of  methyl  mg,  4  temperature  for  0.113 18 h.  mmol).  (40  g,  elution  with  petroleum  ether-diethyl  on  ether;  g  (88%) of the ( Z ) isomer (125).  (film):  1708,  -SnMe.3, 3H,  2j  2  c  1 3  2  Hz  3  C nmr (75.6 3  (t),  ll 23°2 H  5  S n  2  Hz  >.  1  -  4  148.2 2  0.21  l  3  >>  0  2  7  (M -CH ): 3  s  9H  >  CO.  3  -SnMe.3,  2  J  S  n  .  2  4  -°  166.8 426.9742;  -6.8 2  (s),  afforded  3.69  3  (q,  ^sn-C"  ^Sn-C " 57 Hz, 172.3  (s).  found: 426.9747.  (s,  9H,  - 54 Hz), 1.00  H  (q, 2H, - C H C H , J - 7 Hz),  MHz, CDCI3) 6:  (s),  +  <>  2  3  -Sn-C "  51.0  -Sn-H "  - 1  and  This c o l o r l e s s o i l exhibited i r  771 c m ; H nmr (270 MHz, CDC1 ) 6:  - C H C H , J - 7 Hz), 2.35  -OCH3); lj  1191,  silica  19:1)  subjection of the o i l thus obtained to vacuum (0.05 Torr, 2 h ) , 3.88  The  Concentration,  followed by column chromatography of the resultant black o i l gel  2-  mmol) i n 150 mL of dry THF was added  (9.94 mmol) and (PPh ) Pd (130  stirred  3  3  J  S  3  n  3  .  5  c  H z  (t,  (s,  ) > " -  -  6  68  3H, 7  <<1.  Hz),  Exact Mass c a l c d .  for  - 190 Following general procedure 3, the ester (125) (71 was  mg,  0.16  mmol)  converted, after stirring at 85°C for 18 h, into the bis(trimethyl-  stannyl) ester (147). silica  gel  (5  g,  Flash column chromatography of the crude elution  with  o i l on  petroleum ether-diethyl ether;  17:1)  followed by d i s t i l l a t i o n (air-bath temperature 90-95°C/0.05 Torr) of the oil  thus  obtained, afforded 58 mg (82%) of the (E) isomer (147).  colorless o i l exhibited i r (film): 1693, 1224, 772 MHz,  6:  CDC1 ) 3  0.18  (s,  9H,  -SnMe.3, J - H - 54 Hz), 0.98 Sn  2  J  1 1 9  J  S n  _  c  Sn  S n  -  7 Hz), 3.70  2  .  -  57  nmr S n  Hz  - J 3  (111.8 MHz, -  426.9742;  562  Hz).  S n  S n  .  H  X  H  nmr  -= 52 Hz), 0.26  - c ) . 51.7  CDCI3) 5: Exact  (t).  1 4 3  13  = •  C 3 4 0  nmr Hz  1 4  (s), 172.3  4  -50.79 (s, J -Sn *  5 6 2  <<!>.  8  calcd.  for  2H,  3 4  -  <1.  5  (s), 185.6 (s); H  Sn  Mass  (s, 9H,  CDCI3) 6:  (75.6 MHz,  > - -  (400  (q,  3  (s, 3H, -OMe);  (q, ^ s n . c = 342 Hz), -6.1 (q, ^Sn-C  -6.6 2  J  3  2  1  (t, 3H, -CH CH , J - 7 Hz), 2.49  2  -CH CH ,  -SnMe.3, J  cm" ;  This  z  ) • -51,07 (s,  C ]H2302Sn 1;  2  (M -CH ): +  3  found: 426.9741.  Preparation of methyl (Z)- and pentenoate (126) and  (E)-2.3-bis(trimethylstannyl)-4-methyl-2-  (148)  Following general procedure 2,  to  a  stirred  solution of  methyl  4-methyl-2-pentynoate (115) (856 mg, 6.848 mmol) in 90 mL of dry THF added hexamethylditin (6.848 mmol) and (PPh ) Pd (79 3  4  mg,  was  0.068 mmol).  - 191 The  mixture  was  stirred at room temperature for 28 h. Concentration,  followed by column chromatography of the resultant brown o i l gel  on  silica  (35 g, elution with petroleum ether-diethyl ether; 9:1) and subjec-  tion of the o i l thus obtained to vacuum (0.05 Torr; 1 h), afforded g  (90%)  of  the  (Z)  isomer  (126).  This colorless o i l exhibited i r  (film): 1705, 1190, 770 c m ; H nmr (400 MHz, -1  -SnMe ,  2  3  (d, Hz),  J  _  S n  -  H  1  3  53.5 Hz), 0.28 (s, 9H, -SnMe.3, J 2  1 3  340 Hz), -4.5 (q, ^Sn-C 6 Hz), 40.3  (d, J 2  S n  .  170.9 (s), 172.8 (s). 440.9899;  found:  Following  3  "  C  C nmr (75.6 MHz, 3  5  7  2  Hz  >.  2  2  -  7  Exact Mass  6  5  calcd.  Hz  - 51 Hz), 1.04  H  J  2  1  -  2  8  80°C  1 4 6  C H 50 Sn 12  2  2  •  < )-  6  s  (M+-CH3):  2  general procedure 3, the ester (126) (417 mg, 0.914 mmol) stirring  Distillation of the crude o i l (air-bath temperature,  90-95°C/0.05 Torr) afforded 407 mg (98%) of the (E) isomer (148).  MHz,  oil  -SnMe.3,  2j  exhibited  ir  1  2  3  -Sn-H  ~  5  3  -  >>  7  Hz  1  -  1  J -H "  5  2  S n  <>  0  d  6 H  -  7  Hz  )>  °-  MHz,  6:  CDCI3)  3  22.1 (q, J - C " 3  1  S n  3j  -Sn-C  "  (111.8 MHz,  5  9  3  (q,  Hz, J 4  S n  ^sn-C  -  3  ^  1 3  6:  9H  Hz),  -4.4  - C - 6.4 Hz), 43.1  (d,  (q, 2  ^s^c  J  S n  .  c  -  -  337  Hz),  51 Hz, 1 1 9  S n nmr  -44.56 (s, J - S n = 512 Hz), -60.22 (s, I - S n Sn  >  C nmr (75.6  Hz), 51.5 (q), 143.7 (s), 172.7 (s), 184.2 (s);  CDCI3)  s  2  2  -6.2  <>  2 3  - -CH(CH ) , J - 7 Hz), 2.66  (septet, IH, -CH(CH ) , J - 7 Hz), 3.68 (s, 3H, -OMe); 3  This  (film): 1688, 1220, 775 cm" ; % nmr (300  6: 0.20 (s, 9H, -SnMe ,  CDCI3)  "  440.9909.  for 6 h.  colorless  6.5  4j  was converted into the bis(trimethylstannyl) ester (148) after at  -  Hz, -Sn-C  >• 50.9 <q)•  for  9H,  6: -6.3 (q, ^sn-C -  CDCI3) 3j  3  .  3  <q. -Sn-C "  Hz, ISn-C "  S n  (s,  -CH(CH ) ,  2  3.68 (s, 3H, -OMe);  0.25  6:  CDC1 )  6H, -CH(CH ) , J - 6.5 Hz), 2.77 (septet, IH, 3  2.82  Sn  -  - 192 512 Hz).  Exact Mass calcd. for C  H 1 2  25°2  S n  2 (M "CH ): +  3  440.9898;  found:  440.9896.  Preparation of methyl (Z)- and propyl-2-propenoate  (127)  (E)-2.3-bis(trimethvlstannyl)-3-cyclo-  and (149)  Following general procedure 2, 3-cyclopropyl-2-propynoate  (117)  to  a  stirred  solution  of  methyl  (304 mg, 2.45 mmol) i n 40 mL of dry THF  was added hexamethylditin (2.45 mmol) and (PPh ) Pd (50 mg, 0.043 mmol). 3  The  mixture  was  4  s t i r r e d at room temperature for 36 h.  Concentration,  followed by column chromatography of the resultant brown o i l gel  (20 g, e l u t i o n with petroleum ether-diethyl ether;  9:1)  t i o n of the o i l thus obtained to vacuum (0.05 Torr; 1 h ) , mg  (83%)  (film):  of  1703,  2x-SnMe ),  2  3  (tt, c  the 1200,  J_Sn-H  IH, J - 8.5,  12 23°2 H  S n  2  (Z)  isomer  770 c m ' ; 1  "  5  4  Hz  X  This colorless  85°C  5.5 Hz), 3.70  (s,  3H, -OMe).  found:  Exact  916  o i l exhibited i r (s,  > • 0.40-0.48 (m, 2H), 0.66-0.76 (m, 2H), Mass  calcd.  18H, 1.73 for  438.9743.  general procedure 3, the ester (127)  for 7 h.  afforded  3  was converted into the bis(trimethylstannyl) at  silica  and subjec-  H nmr (270 MHz, CDC1 ) 6: 0.23  (M+-CH3): 438.9742;  Following  (127).  on  (412 mg, 0.910 mmol)  ester (149)  after  stirring  D i s t i l l a t i o n of the crude o i l (air-bath temperature,  - 193 1 0 0 ° C / 0 . 0 5 Torr) afforded 344 mg (83%) of the (E) colorless  oil  exhibited  ir  2  2  J  S n  -H "  5  6  Hz  12 23°2 H  S n  2  **  5  4  H z  ) > °-  2  <>  6  s  9H  > • 0.53-0.59 (m, 2H), 0.83-0.91 (m, 2H), 1.78  IH, J - 8.5, 5.5 Hz), c  J_Sn-H  This  nmr (400  1  3  3  (149).  (film): 1685, 1220, 775 c m ' ; ^  MHz, CDC1 ) S: 0.17 (s, 9H, -SnMe.3, -SnMe ,  isomer  (M+-CH3):  3.68  (s,  3H,  438.9742;  -OMe).  Exact  Mass  >  (tt,  calcd.  for  found: 438.9745.  Preparation of methyl (Z)- and ( E ) - 2 . 3 - b i s ( t r i m e t h y l s t a n n y l ) - 7 - t e r t butvldimethvlsiloxv-2-heptenoate  Following  general  (128) and (150)  procedure  2,  to  7-tert-butyldimethylsiloxy-2-heptynoate  a  s t i r r e d s o l u t i o n of methyl  (118) (625 mg, 2.3 mmol)  in  40  mL of dry THF was added hexamethylditin (2.3 mmol) and (PPlvj^Pd (26 mg, 0.023 mmol).  The mixture was s t i r r e d at  Concentration, oil  h),  and  temperature  subjection  with  petroleum  ir  62  h.  ether-diethyl  ether;  of the o i l thus obtained to vacuum (0.05 Torr, 1  afforded 1.13 g (82%) of the (Z) isomer (128).  exhibited  for  followed by column chromatography of the resultant black  on s i l i c a gel (40 g, e l u t i o n  19:1)  room  This  colorless  oil  ( f i l m ) : 1702, 1200, 1100, 840, 740 cm" ; H nmr (400 MHz, 1  CDCI3) 6: 0.05 (s, 6H, B ^ M ^ S i - ) , 0.25 (s, 9H, -SnMe.3, -Sn-H " 2j  5  4  Hz  X  0.24 (s, 9H, -SnMe.3, -Sn-H  > • °-  2j  8  9  <> s  9H  > Bu Me Si-), t  2  =  5  2  Hz  >•  1.36-1.45  - 194 (m, J  3  2H), 1.46-1.55 (m, 2H), 2.35 (t, 2H, a l l y l i c  S  .  n  -  H  -OMe); (q.  1  60 3  J  2  2  C nmr (75.6 MHz, CDC1 ) 6: -6.77 (q, ^ s n - C "  J_  S n  3  .  3  1 Hz  >- " 5  19 41°3 H  2  - 55 Hz, J  1  .  3  c  165.3 ( s ) , 172.3 (s); = 334 Hz),  -37.15  s i l l 8 s n l 2  Following  3  3  8  Hz  °  S  n  -  8  3  <>> s  -  5  9  2  -  6  5  3  6  2  -  oil  J_Sn-Sn  "  3  3  4  Hz  ( M * - ^ ) : 583.0863;  > •  Exact  found:  Mass  calcd.  procedure 3, the ester (128) (427 mg, 0.71 mmol)  ~  5  4  isomer  Hz  )>  ° -  2  (s, 9H, -SnMe.3, J_Sn-H "  5  2  2  a l l y l i c protons, J_s -H " 3  6  0  H z  n  3.70 (s, 3H, -OMe);  1 3  (s,  32.9 ( t ) , 41.6 ( t ,  ) •  3  -  6  1  (m, 2H  19 41°3 H  s i S n  Hz  > - ° -  8  9  X  H  -SnMe , 3  <> s  9H  >  (m, 2H,  > Bu Me Si0CH -, J - 8 Hz), t  2  2  3  4  3  3  2  J  3  3  2  Hz  > » " - <<1> • 5  3  1  - C - 55 Hz - J _ - C > . 3  S n  ( s ) , 184.4 (s);  2  4  2H), 2.44-2.51  8  •  3  5  1  Sn  1 1 9  <> < s  -  7 (  t  2  )  -  5  •  6  9  2  '  W 9  •  2  7  '  - ° <> > C  1  4  3  •  8  S n nmr (111.8MHz, CDCI3) 6: -50.15 (s,  J.Sn-Sn - 562 Hz), -51.54 (s, J_sn-Sn " 562 Hz). c  5  9H,  C nmr (75.6 MHz, CDC1 ) 5: -6.6 (q, ^ s n - C "  -6.1 (q, ^ S n - C =  172.2  This 1  t  (s),  (150).  exhibited i r (film): 1686, 1225, 1100, 840, 770 c m ' ;  B u M e S i - ) , 1.29-1.40 (m, 2H), 1.50-1.59  Hz),  stirring  D i s t i l l a t i o n of the yellow o i l (air-bath temperature  3  J-Sn-H  for  583.0858.  nmr (400 MHz, CDC1 ) 6: 0.04 (s, 6H, B^Me^Si-), 0.15 2  7  - 66 Hz), 51.0 (t) , 62.9 (q) , 148.8 ( s ) ,  c  1 6 0 ° C / 0 . 0 5 Torr) afforded 402 mg (94%) of the (E) colorless  9  S  general  95°C for 12 h.  6  S n nmr (111.8 MHz, CDCI3) 6: -36.47 (s, I n - S n  1 1 9  (s, S n  2  >> " -  was converted into the bis(trimethylstannyl) ester (150) after at  8 Hz,  t  ^Sn-C " 2  -  Hz), 3.60 (t, 2H, Bu Me SiOCH -, J - 8 Hz), 3.70 (s, 3H, 3  40.9 ( t ,  c  protons,  (M+-CH3): 585.0869;  found:  Exact  585.0876.  Mass  calcd.  for  - 195 Preparation of methyl (Z)- and (E)-2.3-bis(trimethylstannyl)-6-tetrahvdropvranvloxv-2-hexenoate  Following  general  (129) and (151)  procedure  2,  6-tetrahydropyranyloxy-2-hexynoate  to  a  s t i r r e d solution of methyl  (119) (365 mg, 1.6 mmol) i n 30 mL of  dry THF was added hexamethylditin (1.6 mmol) and (PPh ) Pd (18 mg, 0.015 3  mmol).  4  The mixture was s t i r r e d at room temperature for 15  h.  Concen-  t r a t i o n , followed by column chromatography of the resultant brown o i l on s i l i c a gel (20 g, e l u t i o n with petroleum ether-diethyl ether;  1:1)  and  subjection of the o i l thus obtained to vacuum (0.05 Torr, 2 h ) , afforded 734 mg (83%) of the (Z) isomer (129). (film):  This colorless o i l  exhibited  ir  1700, 1190, 1030, 780 c m ; H nmr (400 MHz, CDC1 ) 6: 0.25 (s, - 1  X  3  9H, -SnMe , J_s -H = 2  3  5  4  Hz  n  1.47-1.74  (m,  7H),  > • °-  2  1.77-1.89  6  < • s  9 H  -  -SnMe , 3  2  J_s -H  =  5  2  H z  n  )>  (m, IH), 2.35-2.47 (m, 2H, a l l y l i c pro-  tons), 3.38 (dt, IH, J = 10, 6.5 Hz), 3.46-3.53 (m, IH),  3.66-3.74  (m,  IH), 3.70 (s, 3H, -OMe), 3.82-3.89 (m, IH), 4.58 (t, IH, methine proton, J = 3Hz).  Exact  Mass  calcd.  for  C H 0 Sn2 1 7  3 3  4  (M+-CH;}):  541.0423;  found: 541.0425.  Following  general  procedure 3, the ester (129) (705 mg, 1.27 mmol)  was converted into the bis(trimethylstannyl) ester (151) after at  80°C  for  6 h.  stirring  D i s t i l l a t i o n of the crude o i l (air-bath temperature  - 196 1 5 5 ° C / 0 . 0 5 Torr) afforded 652 mg (93%) of the (E) colorless  oil  exhibited  isomer  1  lj  5  4  Hz  3  5  5  Hz  This  i r (film): 1686, 1190, 1030, 780 c m ' ; *H nmr  (400 MHz, CDC1 ) 6: 0.17 (s, 9H, -SnMe.3, -Sn-H " -SnMe.3, ^ S n - H "  (151).  > - °-  2  5  < • s  9H  >  > • 1-48-1.65 (m, 6H), 1.67-1.76 (m, IH), 1.79-1.90  (m, IH), 2.51-2.62 (m, 2H, a l l y l i c protons), 3.41 (dt, IH,  J  -  10,  7  Hz), 3.47-3.55 (m, IH), 3.70 (s, 3H, -OMe), 3.75 (dt, IH, J - 10, 7 Hz), 3.82-3.90 (m, IH), 4.6 (t, IH, methine proton, J - 4 c a l c d . for C H 3 0 S n 1 7  3  4  2  (M+-CH3):  541.0423;  Hz).  Exact  Mass  found: 541.0426.  Preparation of methyl (Z)- and ( E ) - 2 . 3 - b i s ( t r i m e t h y l s t a n n y l ) - 4 - t e r t butyldimethylsiloxv-2-butenoate  (130) and (152)  130 Following  general  152  procedure  2,  4-tert-butyldimethylsiloxy-2-butynoate mL mg,  of  to  a  stirred  solution of ethyl  (116) (205 mg, 0.847 mmol) i n  13  dry THF was added hexamethylditin (0.847 mmol) and (PPl^^Pd (13  0.011  mmol).  Concentration,  The mixture  was  stirred  at  55-60°C  for  4  h.  followed by column chromatography of the resultant brown  o i l on s i l i c a gel (10 g, e l u t i o n  with  petroleum  ether-diethyl  ether;  9:1) and subjection of the o i l thus obtained to vacuum (0.05 Torr, 1 h ) , afforded 403 mg (83%) of the exhibited  ir  (Z)  isomer  (130).  This  colorless  oil  ( f i l m ) : 1698, 1170, 1060, 840, 770 cm" ; ^ nmr (270 MHz, 1  CDCI3) 6: 0.03 (s, 6H, B^Me^Si-), 0.20 (s, 9H, -SnMe.3, ^Sn-H " 2  5  6  Hz  >>  - 197 -  0.23  (s, 9H, -SnMe ,  3H,  - 0 C H C H , J - 7 Hz), 4.10 (q, 2H, -OCH CH , J - 7 Hz), 4.35 (s, 2H, 2  2  (q),  J  3  2  6:  3  S  .  n  - 56 Hz), 0.87 (s, 9H, B u M e S i - ) . 1-26 2  - H - 40 Hz, J 4  S n  -6.5  (q,  -  S n  -H ~  1  1  345 Hz),  3  Hz  >>  -5.8  1  3  c  n  J-Sn-C - 76 Hz), 147.1 (s) , 166.1 (s) , 171.6 ( s ) . 1 7  3 7  3  (M+-CH5): 557.0556;  2  found:  m  (q,  14.5 (q), 18.4 ( s ) , 26.0 (q), 60.1 ( t ) , 68.0 (t,  C H 0 SiSn  J  2  S  r  (75.6 MHz,  -  337 Hz) ,  .  n  -  c  Exact Mass c a l c d . for  557.0549.  silica  gel  (10  Flash column chromatography g,  elution  of  the  yellow  o i l on  with petroleum e t h e r - d i e t h y l ether; 97:3)  followed by d i s t i l l a t i o n (air-bath temperature 1 3 5 ° C / 0 . 0 5 Torr) oil  nmr  MHz, CDCI3)  (270  S n  _  6: 0.06 (s,  6H, B u M e S i O - ) , 0.15 (s, 2  2  2  2  t  2  2j  nmr -  Hz), 0.89  3  2  J  S  n  .  - 44 Hz, J 4  H  3  4  5 Hz  S n  4  1  H  z  - -Sn-C 3j  =  6  1  H z  >.  1  4  4  - < >. 9  s  1  7  1  - < >. 9  s  -H  > • "  342 Hz), -5.1 (q), 14.2 (q), 18.2 ( s ) , 26.0 (q), 60.8 "  1  1  (s,  9H,  2  nmr (75.6 MHz, C D C I 3 ) 5 : -6.1 (q, -"-Jsn-C "  -Sn-C  cm" ; H  3  = 7 Hz), 4.34 (s, 2H, Bu Me SiOCH -, C  50  =  This  1.26 ( t , 3H, - 0 C H C H , J •= 7 Hz), 4.11 (q, 2H, -OCH CH , J  t  -  the  9H, -SnMe.3,  t  •= 54 Hz), 0.24 (s, 9H, -SnMe.3, ^Sn-H  H  Bu Me SiO-),  1 3  of  thus obtained, afforded 140 mg (86%) of the (E) isomer (130).  c o l o r l e s s o i l exhibited i r (film): 1698, 1640, 1230, 845, 780  J  mmol)  converted into the bis(trimethylstannyl) ester (152) after s t i r r i n g  at 81°C for 12 h .  2  -5.3  35 Hz,  Following general procedure 3, the ester (130) (162 mg, 0.283 was  (t,  t  H  2  t  CDC1 )  J  3  Bu Me SiOCH -,  3  2  3  -  0  (t), - <> •  found:  557.0556.  Mass  c a l c d . for C H 0 S i S n 1 7  3 7  3  2  s  lj  >>  -Sn-C  69.9 1  1  (t,  S n  Exact  4  Hz  (111.8 MHz, C D C I 3 ) 6: -47.06 (s, J.s -Sn " 510 Hz), -48.80 (s, I Hz).  7  1  s  510  7  6  1  9  n  1  "  3  n  -Sn  (M+-CH3): 557.0556;  - 198 Preparation of methyl (Z)- and (E)-2.3-bis(trimethylstannyl)-5-(2-cvclopentenyl)-2-pentenoate (131) and (153)  Me Sn  SnMe  3  Me Sn  3  C0 Me  3  2  SnMe  C0 Me 2  Following  general  procedure  2,  to  a  3  s t i r r e d solution of methyl  5-(2-cyclopentenyl)-2-pentynoate (120) (122 mg, 0.685 mmol) i n 15 mL of dry  THF was  0.007 mmol).  added  hexamethylditin  The reaction mixture  (0.685 mmol) and (PPl^^Pd (8 mg,  was  stirred  at  reflux  for  6  h.  Concentration, followed by column chromatography of the resultant o i l on s i l i c a gel (5 g, e l u t i o n with petroleum ether-diethyl ether; subjection  of  the  oil  thus  afforded 255 mg (73%) of the exhibited  ir  (film):  0.23 (s, 9H, -SnMe.3, Hz),  2  J  obtained (Z)  17:3)  to vacuum (0.05 Torr, 45 min),  isomer  (131).  This  colorless  oil  1700, 1200, 770 c m ; H nmr (400 MHz, CDC1 ) 5: - 1  X  3  S n  - H "*  5  4  Hz  >• ° -  2 4  ( s  9H  >  -SnMe.3,  2  J  S  n  .  55  H  1.29-1.50 (m, 4H), 1.97-2.08 (m, IH), 2.20-2.40 (m, 4H), 2.59-2.69  (m, IH), 3.70 (s, 3H, -OMe), 5.63-5.75 (m, 2H, v i n y l Mass c a l c d . for C H 9 0 S n 1 6  Following  2  2  2  (M+'C^): 493.0212;  protons).  80°C  for  general procedure 3, the ester (131) (158 mg, 0.311 mmol)  8  h.  Distillation  of  the  oil  1 3 0 ° C / 0 . 0 5 Torr) afforded 128 mg (81%) of the (E) colorless  oil  Exact  found: 493.0216.  was converted into the bis(trimethylstannyl) ester (153) after at  and  exhibited  ir  stirring  (air-bath temperature isomer  (153).  This  (film): 1685, 1225, 775 c m ; H nmr (400 - 1  X  - 199 -  MHz, CDCI3) 6: 0.15 (s, 9H, -SnMe.3, -SnMe.3, (m,  J  2  S  n  .  2  J  S  n  .  -  H  54  Hz),  0.25  3H,  9H,  - 54 Hz), 1.24-1.40 (m, 2H) , 1.40-1.51 (m, IH), 2.00-2.11  H  IH), 2.22-2.41 (m, 2H), 2.46-2.56 (m, 2H), 2.74-2.83 (m,  (s,  (s,  -OMe), 5.66-5.87 (m, 2H, v i n y l protons);  CDCI3) 6: -50.24 ( J - S n " 564 Hz), -51.82 (s, J S n  Mass c a l c d . for C H 9 0 S n 2 (M+-CH ): 16  2  2  S  n  493.0212;  3  1 1 9  .  S  n  IH),  3.70  S n nmr (111.8 MHz, " 564 Hz).  Exact  found: 493.0218.  Preparation of methyl (Z)- and ( E ) - 2 . 3 - b i s ( t r i m e t h y l s t a n n y l ) - 4 - ( 3 - c v c l o hexenvl)-2-butenoate (132) and (154)  Following  general  procedure  2,  to  a  s t i r r e d s o l u t i o n of methyl  4-(3-cyclohexenyl)-2-butynoate (121) (89 mg, 0.5 mmol) i n 8 THF  was  mmol).  added  hexamethylditin  (0.5  mL of  mmol) and (PPt^^Pd (8 mg, 0.007  The reaction mixture was s t i r r e d at reflux for 6 h .  tion,  followed  Concentra-  by column chromatography of the resultant o i l on s i l i c a  gel (5 g, e l u t i o n with petroleum e t h e r - d i e t h y l ether; 17:3) and tion  of  the  9H,  1.07-1.19 2H),  1703,  -SnMe.3,  2  J  subjec-  o i l thus obtained to vacuum (0.05 T o r r , 45 min), afforded  188 mg (74%) of the (Z) isomer (132). (film):  dry  1640,  S n  (m,  -H "  1190, 5  1  •  5 Hz  This pale yellow o i l exhibited i r  780 cm" ; H nmr (400 MHz, CDCI3)  > • °-  1  2 0  X  <- > s  9H  - M§.3. ISn-H " Sn  2  6: 0.18  (s,  53.5 Hz),  IH), 1.51-1.72 (m, 3H), 1.88-2.06 (m, 3H), 2.21-2.38 (m,  3.63 (s, 3H, -OMe), 5.58-5.62 (m, 2H, v i n y l i c  protons);  1 3  C nmr  - 200 -  (75.6  Hz),  25.4 ( t ) ,  ^Sn-C  2  CDCI3)  MHz,  (s),  ~  6:  (q, ^ S n - C ~  28.3 ( t ) , 31.5 ( t ) ,  53 Hz, J 3  163.7 (s),  493.0212;  -6.6  S n  -C  =  6  4  33.9 (d,  Hz), *  0  3  J  S  .  n  6  -  ^Sn-C  5  - 6.6 Hz),  c  47.7  Exact Mass c a l c d . for C H 9 0 S n 1 6  2  2  88°C  -1  for  48  0.20 3H), (m,  This X  h.  Distillation  colorless  of  the  (s,  9H, -SnMe.3,  1.90-2.05  2  3j  (d), c  -Sn-C  J  S n  of  7  S n  2  (E)  isomer  2  J  S n  - H = 52.5 Hz),  3H, -OMe),  5.55-5.65  C nmr (75.6 MHz, CDCI3) 5: -6.2 (q, ^ s n - C "  1 3  3  4  Hz), 47.8 (t,  (W^-O^):  the  - H " 54 Hz), 1.07-1.20 (m, IH), 1.58-1.71 (m,  (m, 3H), 2.36-2.53 (m, 2H), 3.65 (s,  127.1 (d), 144.7 (s),  16 29°2 H  =  stirring  pale yellow o i l (air-bath  H nmr (400 MHz, CDCI3) 6: 0.10 (s, 9H, -SnMe.3,  342 Hz), -5.5 (q, ^ s n - C " d  (t,  o i l exhibited i r ( f i l m ) : 1685, 1640, 1220, 775  2H, v i n y l i c protons);  <>  1  general procedure 3, the ester (132) (170 mg, 0.335 mmol)  temperature 1 5 0 ° C / 0 . 0 5 Torr) afforded 150 mg (88%)  cm ;  3  (M+'C^):  2  was converted into the bis(trimethylstannyl) ester (154) after  (154).  3  found: 493.0209.  Following  at  =  Hz), 50.9 (q), 126.5 (d), 126.8 (d), 149.9  5  172.4 (s).  3  0  Hz  3  >•  J  S n  2  5  4  < >• c  2  - C = 52 Hz -  171.7 (s),  493.0212;  -  8  2  4  •  J -c). S n  184.2 (s).  found: 493.0206.  3  1  -  7  ^ •  3  4  -  2  51.7 (q), 126.3  Exact Mass c a l c d .  for  - 201 Preparation of methyl (Z)- and CE)-2.3-bis(trimethylstannyl)-2.6-heptadienoate (133)  and (155)  1 55 Following  general  procedure  2,  to  a  s t i r r e d solution of methyl  6-hepten-2-ynoate (111)  (350 mg, 2.53 mmol) i n 39  added  (2.53  hexamethylditin  mmol)  by  gel (20  dry  THF was  and (PPt^^Pd (52 mg, 0.045 mmol).  The reaction mixture was s t i r r e d at followed  mL of  reflux  for  4  h.  Concentration,  column chromatography of the resultant black o i l on s i l i c a  g,  elution  with  petroleum  ether-diethyl  ether;  17:3)  and  subjection of the o i l thus obtained to vacuum (0.05 Torr, 1 h ) , afforded 1.003  g (85%) of the (Z) isomer (135).  (film): 9H,  1708,  -SnMe.3, J qd, 2  Hz),  5.01  10, 7 Hz);  (s),  (s,  3  S n  -H =  2  3  J  S n  5  2  H z  ) • °-  2  2  (s,  2  ( .  2 4 5  CH CHCH CH -,  3.69  s  J  2  -  7,  3H, -OMe), 4.95  1.5  1 3  C nmr (75.6 MHz, CDCI3) 6: 3  3  2  H z  >.  3  4  -  3  3  (s).  S n  Hz),  -H =  B  -6.8  1 3  2 5  -  > •  2  -  n  (m, 2H,  10,  ^Sn-C ~  (t), 2  Hz  2,  1.5  c  i S n - C - 8 Hz), 40.3  Exact Mass c a l c d . for C H 0 S n  4  (ddt, IH, H , J - 17,  (q,  (d), 137.6  5  2.38-2.45  (ddt, IH, H , J  A  - C - 66 Hz), 50.9 (q), 114.7  172.1  9H, -SnMe.3, J  (ddt, IH, H , J - 17, 2, 1.5 Hz), 5.80  (q, ^ s n - c -  -6.7 Hz,  1641, 1191, 770 cm" ; ^-H nmr (400 MHz, CDC1 ) 6: 0.24  2H,  CH CHCH CH -), 2  ir  1  2  (broad  This colorless o i l exhibited  (t,  2  J  149.6 2  S  3  3  9  n  .  C  (s),  Hz  >>  - 55 164.5  (M+-CH ): 452.9899; 3  found: 452.9896. Following general procedure 3, the ester (135) was  (155 mg,  0.33  mmol)  converted into the bis(trimethylstannyl) ester (155) after s t i r r i n g  - 202 at 80°C for 14 h. silica  gel  (5  Flash column chromatography g,  elution  with  of  oil  thus  (400  9H,  MHz, CDC1 ) 6: 0.16 .  2  2.53-2.61  S  n  H  - 54 Hz), 2.05 2  2  J  S  n  .  c  172.1  (s),  -  551  c  13 25°2 H  55  S n  2  2  (s,  -  2  (s);  -51.62 (M "-^): 4  J  S n  1 3  -c).  1 1 9  (s,  5  770 3  Hz  17:3)  Torr)  of  51.8  cm" ;  > >°-  3H, -OMe), 5.00  n  452.9898;  X  6  <> s  (ddt, IH, H ,  Hz),  (q),  (t,  115.0  3  J  S n  (d),  -C  c  B  5.69  =  551  Hz).  (ddt,  (q, -"-Jsn-C  8 Hz), 40.8  137.0  (t),  (t,  144.6  S n nmr (111.8MHz, CDCI3) 6: -50.96 (s, J_s -Sn  2  H  1  2  C nmr (75.6 MHz, CDCI3) 6: -6.5  Preparation of methvl (Z)- and 2.8-nonadienoate (134)  2  A  3  183.7  Hz),  on  (qd, 2H, CH CHCH CH -, J - 7, 1.5 Hz),  (q, ^ s n . c - 40 Hz), 34.4 Hz  1229,  2  2  c  344 Hz), -6.0  1641,  (ddt, IH, H , J = 17, 2, 1.5  IH, H , J - 17, 10, 7 Hz);  3  95-100°C/0.05  9H, -SnMe.3, ^Sn-H "  (m, 2H, CH CHCH CH -), 3.70  J - 10, 2, 1.5 Hz), 5.04  -  (s,  3  -SnMe.3, J  oil  obtained, afforded 125 mg (81%) of the (E) isomer (155).  This c o l o r l e s s o i l exhibited i r (film): 1692, nmr  yellow  petroleum ether-diethyl ether;  followed by d i s t i l l a t i o n (air-bath temperature the  the  (s),  I n-Sn S  Exact Mass c a l c d .  for  found: 452.9907.  (E)-2.3-bis(trimethylstannyl)-8-bromo-  and (156)  To a s t i r r e d solution of palladium(II)acetate  (2.7 mg, 3 mol%) i n  1  - 203 -  mL of dry THF was added triphenylphosphine (6.4 mg, 6 mol%) and t r i e t h y lamine (114 jiL, 0.816 mmol). for  1  After the mixture had been s t i r r e d at 60°C  h hexamethylditin (0.408 mmol) and a solution of methyl 8-bromo-  non-8-en-2-ynoate (108)  (100 mg, 0.408 mmol) i n 1  added to the red s o l u t i o n . reflux for 2 h. resultant  (0.05  Torr,  (400  9H,  -SnMe.3,  o i l on s i l i c a gel (10 g, e l u t i o n with petroleum ether-  9:1) 45  and subjection of the o i l thus  min),  afforded  MHz, CDC1 ) 6: 0.23 -Sn-H  "  5  5  Hz  )>  CH CBrCH CH -, J - 8 Hz), 2.35 2  (t,  2  proton,  1-22-1.32  J  2  -  2  Hz),  (75.4  MHz, CDCI3) 6:  Hz),  27.6  3j  2  2H, CH CBrCH -, J = 8 Hz), 3.70 2  -Sn-C "  164.9  6  (t), 6  (s),  Hz  >-  5.56  -6.75  28.8 4 i  172.2  -l  3  J  S n  (m,  2  (s,  1191,  -H  _  5  2H) ,  770  3  Hz  cm* ; 1  )>  °-  1.55  2  3  2  5  338 Hz),  (d, IH,  =7.6  (q),  116.5  -6.67  Hz), 40.6 (d),  (t,  134.2  2  J  2 8  7 9 2  S  H  (> s  n  .  c  1 3  C nmr -  2  330  -= 55 Hz,  149.2  BrSn  2.42  vinylic  ^s^c  (d),  Exact Mass c a l c d . for C H 0 1 5  (q,  X  (quintet,  2  3H, -OMe), 5.39  -C  S n  vacuum  2H, C H C B r ( C H ) C H - , J - 8 Hz),  ^sn-C -  ( O , 51.0 (s).  to  (d, IH, v i n y l i c proton, J - 2 Hz);  (q,  (t,  1630,  9H, -SnMe.3, J  (t,  2  obtained  149 mg (64%) of the (Z) isomer (134).  (s,  3  2j  THF was  The r e s u l t i n g yellow solution was s t i r r e d at  This c o l o r l e s s o i l exhibited i r ( f i l m ) : 1708, nmr  dry  Concentration, followed by column chromatography of the  black  d i e t h y l ether;  mL of  (s),  (M+-CH ): 3  558.9317; found: 558.9312.  Following general procedure 3, the ester (134) was  converted into the bis(trimethylstannyl)  at 83°C for 36 h. silica  gel  (10  (80 mg,  ester (156)  0.139  mmol)  after s t i r r i n g  Flash column chromatography of the pale yellow o i l on g,  elution  with  petroleum e t h e r - d i e t h y l ether;  followed by d i s t i l l a t i o n (air-bath temperature 1 4 5 ° C / 0 . 0 5 Torr)  of  9:1) the  - 204 -  oil  thus  obtained, afforded 53 mg (66%) of the (E) isomer (156).  c o l o r l e s s o i l exhibited i r (film): 1691, 1630, 1226, 770 (400  MHz, CDC1 ) 5: 0.17 (s, 9H, -SnMe.3,  -SnMe ,  2  3  I  -H  S n  CH CBrCH CH , 2  3H,  2  J  proton,  -Sn-C "  <t.  2  "  5  4  -  H z  ).  1-26-1.37  3j  3  4  1  H z  ).  6  -  -Sn-C - 55 Hz -  3  1.5 Hz);  1 3  <q. -Sn-C ~  0  lj  J -C>>  5  Sn  172.1 ( s ) , 183.8 ( s ) . 560.9298;  2H),  5  2  Hz  ^-H nmr  - 1  > • ° -  1.60  2  7  <> s  (quintet,  9H  >  2H,  8 Hz), 2.39-2.53 (m, 4H, a l l y l i c protons), 3.70 (s,  J -  -Sn-H "  (m,  -OMe), 5.41 (d, IH, v i n y l i c proton,  vinylic lj  2j  3  cm ;  This  1  -  7  5.57  (d, IH,  C nmr (75.4 MHz, CDCI3) 6:  -6.5 (q,  3  4  0  (O-  J  H z  1  -  ) 1  6  Exact Mass c a l c d .  2  -  7  7  1.5  -  <> •  8  fc  ( >• d  for C  Hz),  1 5  1  H  2  3  4  2 8  0  -  9  2  8 1 2  -  2  <*> .  ( >d  BrSn  1  4  4  1-  4  -  3  ( ).  2  s  (M -CH ): +  2  3  found: 560.9306.  Preparation of ethvl  (Z)-2.3-bis(trimethylstannyl)-5-chloro-2-  pentenoate (135)  Cl  Following  general  5-chloro-2-pentynoate added  hexamethylditin  procedure  2,  to  chromatography  stirred  (122) (742 mg, 4.64 mmol) i n (4.64  mmol)  of  60  solution of ethyl mL of  THF was  and (PPI^^Pd (65 mg, 0.056 mmol).  The mixture was s t i r r e d at reflux for 6 h. column  a  Concentration,  followed  the resultant crude o i l on s i l i c a gel (35 g,  e l u t i o n with petroleum ether-diethyl ether; 23:2) and subjection of oil  by  the  thus obtained to vacuum (0.05 Torr; 1.5 h ) , afforded 2.02 g (89%) of  - 205 the (Z) isomer (135). 1186,  773 c m ; - 1  56 Hz), 0.28 7  Hz), 2  2  H nmr (400 MHz, CDC1 ) 6: 0.27 9H, -SnMe.3,  (t,  2  3 5 2  ClSn  Preparation of ethvl  S  n  .  - 54 Hz), 1.31  H  2  S  .  n  ir  (film): 2  (t,  3H, -OCH CH , J 2  (M+-CH ): 474.9509;  found: 474.9530.  2  3  3  7  Hz).  (t, 2H,  -  2  3  - 54 Hz), 3.52  H  1702,  9H, -SnMe.3, ^Sn-H "  (q, 2H, -0CH CH , J  Exact  (136)  SnMe,  3  C0 Et 2  Br Following  general  5-bromo-2-pentynoate hexamethylditin  procedure  (104)  (1.69  2,  to  a  stirred  and  (PPh ) Pd  mixture was s t i r r e d at reflux  for  8  chromatography  solution of ethyl  (347 mg, 1.69 mmol) i n 20 mL of THF was added  mmol)  of  3  h.  4  (39 mg, 0.034 mmol).  Concentration,  thus  770 c m ; - 1  56 Hz), 0.28 7  C  (s,  Hz), 2.84 (t,  Hz), 1 2  H  4.15 2 4  0  8 1 2  by  the resultant black o i l on s i l i c a gel (20 g, of  the  obtained to vacuum (0.05 Torr; 1 h ) , afforded 600 mg (66%) of  the (Z) isomer (136). 1186,  The  followed  e l u t i o n with petroleum ether-diethyl ether; 9:1) and subjection oil  Mass  (Z)-2.3-bis(trimethvlstannvl)-5-bromo-2-  Me Sn  column  (s,  3  2  c a l c d . for C H 4 0 1 2  J  2  2H, C1CH CH -, J - 8 Hz, I  J - 8 Hz), 4.19  pentenoate  exhibited  3  (s,  2.79  C1CH CH -,  X  This colorless o i l  X  9H, -SnMe ,  2  3  (s,  J _ s - H " 54 Hz), 1.28 n  2H, B r C H C H - , J - 8 Hz), 3.32 (t, 2  2  -0CH CH , 2  3  J  ( M - C H ) : 520.8985; +  2  exhibited  H nmr (270 MHz, CDCI3) 6: 0.26  (q, 2H, BrSn  This colorless o i l  3  -  7  Hz).  ir  (film):  9H, -SnMe.3, (t,  2  J  1698, S n  -H  -  3H, -0CH CH , J 2  3  2H, B r C H C H - , J - 8  Exact  found: 520.8982.  2  Mass  2  calcd.  for  - 206 Preparation of methyl (Z)- and (E)-2.3-bis(trimethylstannyl)-6-chloro-2hexenoate (137) and (146)  Following  general  6-chloro-2-hexynoate added  procedure  2,  to  a  (100) (1.00 mg, 6.25 mmol) i n  hexamethylditin  (6.25  mmol)  chromatography  of  80  mL of  THF was  and (PPl^^Pd (72 mg, 0.062 mmol).  The mixture was s t i r r e d at reflux for 5 h. column  s t i r r e d solution of methyl  Concentration,  followed  by  the resultant black o i l on s i l i c a gel (40 g,  e l u t i o n with petroleum ether-diethyl ether; 19:1) and subjection of oil  thus  obtained to vacuum (0.05 Torr; 2 h ) , afforded 2.62 g (86%) of  the (Z) isomer (137). 1195,  This colorless o i l  exhibited  ir  (film):  1698,  770 cm" ; H nmr (400 MHz, CDCI3) 6: 0.25 (s, 9H, -SnMe.3, J 1  X  2  54 Hz), 0.26 (s, 9H, C1CH CH CH -, 2  2  J  2  -SnMe.3,  2j  -Sn-H  ~  5  Hz) •  1  1  >  8  S  n  (quintet,  5  - 8 Hz), 2.47 (t, 2H, C1CH CH CH -, J = 8 Hz, J 3  2  2  2  2  difference  2  experiment,  S n  "  38.2 (t, 163.2 J C  S  n  1 2  .  S  H  2  J  (s),  3  S  n  7  .  Hz  )>  " 6  6  9  (s);  C nmr (75.6 MHz, CDCI3) 6: -6.74  lj  3  172.1  1 3  <q- -Sn-C "  - 55 Hz, J  C  S n  0  3 5 2  ClSn  2  -H " a  i r r a d i a t i o n at 6 3.70 (-OMe) caused signal  -C "  1 1 9  6  3  S n nmr  (M+-CH3): 474.9509;  3  3  Hz),  3  2  -  8  3j  -Sn-C "  7  (q,  Hz),  Hz), 44.4 ( t ) , 51.1 (q), 150.8 (s),  6  - 317 Hz), -35.46 (Isn-Sn "  n  2 4  3  =  H  In  2  enhancement at 5 0.25 (aSnMe.3); ^Sn-C  .  2H,  55 Hz), 3.51 (t, 2H, C1CH CH CH -, J - 8 Hz), 3.70 (s, 3H, -OMe); nOe  the  3  1  (111.8 MHz, CDCI3) 6: 7  Hz  >•  Exact  found: 474.9518.  Mass  -35.26 (s, calcd.  for  - 207 Following  general procedure 3, the ester (137)  was converted into the bis(trimethylstannyl) at  75°C  for  24  h.  Distillation  of  ester (146)  the  temperature 1 0 5 ° C / 0 . 1 Torr) afforded 457 mg (146).  (s,  3  (m,  -SnMe ,  2  3  J  S n  _  Hz),  3.71  5 3.71  (s,  2  2  3  J_s -H "  2  6  0  Hz  n  3H, OMe):  >>  3  -  5  S n  ^Sn-c)-  4 4  -  3  (t,  (t>  5  3  J  S  n  .  c  -6.4  Exact  stirring  (E)  1220,  - H - 54  2  1  Hz), 2  2.60-2.66  2  2  2  H  2 4  0  3 5 2  7  2  i r r a d i a t i o n at  (-SnMe.3) and  6  0.26  (q, ^ s ^ c - 346 Hz),  -6.0  2  J  S  n  .  c  -  55 1 1 9  S n  1 2  (s,  H , C1CH CH CH -, J -  = B Hz), 39.0 (t,  c a l c d . for C  X  0.26  -49.29 (s, J - S n " 527 Hz), -50.17 (s, J  Mass  isomer  775 cm" ; H  51.8 (q), 145.5 (s) , 172.0 (s), 182.3 (s);  (111.8 MHz, CDCI3) 5: Hz).  the  In a nOe difference experiment,  C nmr (75.6 MHz, CDCI3) 6:  1 3  lj  found:  of  2  ( -Sn-C ~ 341 Hz), 33.0  527  9H, -SnMe.3, J  (-OMe) caused signal enhancement at 6 0.17  (-SnMe.3);  3  (96%)  - 55 Hz), 1.73-1.82 (m, 2H, C1CH CH CH -),  H  2H, C1CH CH CH -, 2  after  pale yellow o i l (air-bath  This colorless o i l exhibited i r (film): 1685,  nmr (400 MHz, CDC1 ) S 0.17 9H,  (477 mg, 0.973 mmol)  ClSn  2  (M+-CH3):  Hz  =  S n nmr S  n  .  S  n  "  474.9509;  474.9510.  Preparation of methyl hexenoate  (Z)-2.3-bis(trimethylstannvl)-6-bromo-2-  (138)  Br Following general procedure 2, 6-bromo-2-hexynoate  (101)  to  a  stirred  solution  of  methyl  (644 mg, 3.14 mmol) i n 40 mL of THF was added  - 208 hexamethylditin (3.14 mmol) and (PPl^^Pd mixture  was  stirred  at  reflux  for  (50  6 h.  mg,  0.043  oil  with petroleum ether-diethyl ether; 19:1)  (Z)  1200,  isomer  (138).  (30  g,  and subjection of the  780 cm" ;  nmr (400 MHz, CDC1 ) 6: 0.25  1  Hz),  0.26  This colorless o i l exhibited i r (film):  2  2  (s,  3  (s,  9H,  -SnMe.3,  BrCH CH CH -, J - 7.5 Hz), 2.47 -  gel  thus obtained to vacuum (0.05 Torr; 1.5 h ) , afforded 1.41 g (84%) of  the  55  The  Concentration, followed by  column chromatography of the resultant crude o i l on s i l i c a elution  mmol).  (t,  2  55  Hz),  3.38  (t,  Exact  Mass  calcd.  2  J  S  n  .  -  H  9H, -SnMe.3, -Sn-H " 2j  54 Hz), 1.93  (quintet, 2H,  2H, BrCH CH CH -, J - 7.5 Hz, 2  2  for  2  C H 40 1 2  2  8 1 2  2  BrSn  (M -CH ): +  2  3  2  2H, BrCH CH CH -, J - 7.5 Hz), 3.71 (s, 2  1700,  3  J  S n  -H  3H, -OMe).  520.8985;  found:  520.8988.  Preparation of methyl  (Z)-2.3-bis(trimethylstannyl)-6-iodo-2-hexenoate  (139)  Following  general  6-iodo-2-hexynoate (102) added  procedure  to  a  s t i r r e d solution of methyl  (756 mg, 3.0 mmol) i n 45  mL of  dry  THF was  hexamethylditin (3.0 mmol) and (PPl^^Pd (75 mg, 0.06 mmol).  mixture was s t i r r e d at reflux column  2,  chromatography  of  for  6  h.  Concentration,  followed  The by  the resultant black o i l on s i l i c a gel (50 g,  e l u t i o n with petroleum ether-diethyl ether; 23:2)  and subjection of  the  - 209 oil  thus obtained to vacuum (0.05 Torr; 1.5 h ) , afforded 1.37 g (79%) of  the (Z) isomer (139). 1190,  This colorless o i l  exhibited  771 cm" ; H nmr (400 MHz, CDC1 ) 6: 0.245 (s, 1  X  3  - 56 Hz), 0.25  (s,  9H, -SnMe , 3  2  J  S  .  H  -  54  Hz),  1 - 8 Hz), 2.42  Hz),  2H, I C H C H C H - , J - 8 Hz), 3.71  2  2  2  3.15  (t,  2  2  Mass c a l c d . for C H 0 I S n 1 2  2 4  2  (t,  n  ICH CH CH -,  heptenoate (140)  Following  2  general  procedure  (123)  hexamethylditin  2,  to  a  chromatography  1290, S n  3H,  S n  -H  2H,  - H - 56  -OMe).  Exact  found: 566.8882.  (600 mg, 2.74 mmol) i n 40 mL of dry  (2.74  mmol)  of  THF was  and (PPl^^Pd (50 mg, 0.043 mmol). Concentration,  followed  by  the resultant black o i l on s i l i c a gel (45 g, and subjection of  the  thus obtained to vacuum (0.05 Torr; 1.5 h ) , afforded 1.17 g (78%) of  the (Z) isomer (140).  J  S n  s t i r r e d solution of methyl  e l u t i o n with petroleum ether-diethyl ether; 19:1)  2  J  (quintet,  2  (s,  2  (E)-2.3-bis(trimethylstannyl)-7-bromo-2-  The mixture was s t i r r e d at reflux for 5 h. column  1.91  1705,  and (157)  7-bromo-2-heptynoate added  9H, -SnMe.3,  3  2  (M+-CH3): 566.8867;  2  (film):  2H, I C H C H C H - , J = 8 Hz, J  2  Preparation of methyl (Z)- and  oil  ir  770  cm' ; 1  X  This colorless o i l exhibited  H nmr (400 MHz, CDCI3) 6: 0.25  - H - 54 Hz), 1.48-1.57 (m, 2H), 1.86  (quintet,  ir (s,  (film):  1698,  18H, 2 x -SnMe.3,  2H, J - 7  Hz),  2.36  - 210 -  (t, J lj  2H, a l l y l i c protons, J - 7 Hz, I s n - H ~ 3  -  7  Hz), 3.70  -Sn-C "  3  4  2  H z  >.  (s,  - 6  32.3  (t),  33.6 ( t ) ,  149.7  (s),  164.4  (M -CH ):  (s),  534.9141;  +  3  Following  3H, -OMe); <q-  7  lj  1 3  172.1  J  2  S  n  .  (s).  found:  7  H z  ) •  -  3  4  0  2H  >  BrCH -, 2  C nmr (75.6 MHz, CDC1 ) 6: -6.8  (q,  3  -Sn-C "  39.8 (t,  5  3  2  7  H z  >.  2  8  -  3  - 55 Hz, J  (t,  3  c  S n  3  J-Sn-C  -C "  6  6  "  H z  Exact Mass calcd. for  8  ).  Hz  > •  51.0  C H 0 1 3  2 6  (q),  7 9 2  BrSn  2  534.9148.  general procedure 3, the ester (140)  (101 mg, 0.184 mmol)  was converted into the bis(trimethylstannyl) ester (157), after s t i r r i n g 40  h  at  85°C.  Flash column chromatography of the pale yellow o i l on  s i l i c a gel (10 g, e l u t i o n followed  by  with  petroleum  ether-diethyl  ether;  d i s t i l l a t i o n (air-bath temperature 1 3 0 ° C / 0 . 0 5 Torr) of the  o i l thus obtained, afforded 81 mg (80%) of the (E) isomer colorless  oil  exhibited  MHz, CDC1 ) 6: 0.17  (s,  3  -SnMe ,  2  3  J  S n  -H  ir  (film): 1692,  9H, -SnMe ,  2  3  J  S n  2  2  J . - 7 Hz), 3.71 (s,  -6.5  (q, i j g n . c = 341 Hz), -6.0  7.1  Hz),  (q),  144.6  C H 0 1 3  32.7  2 6  7 9 2  (s),  BrSn  2  .  1224,  -  H  (t),  33.3 ( t ) ,  172.0 (M+-CH ): 3  (s),  3  J  S n  52.5  -H  3H, -OMe); (q, l j 40.7 183.5  532.9161;  S n  _  (t,  1 3  =  (157).  This  770 c m ' ; H nmr (400  ~ 53.5 Hz), 1.42-1.52 (m, 2H), 1.91  Hz), 2.47-2.54 (m, 2H, a l l y l i c protons, BrCH CH -,  17:1)  1  Hz),  X  0.26  (quintet,  59 Hz),  (s,  9H,  2H, J •= 7  3.42  (t,  2H,  C nmr (75.6 MHz, CDC1 ) 8: 3  = 340 Hz), 28.9  c  2  J  S n  (s). found:  - C - 54 Hz Exact  Mass  532.9164.  (t, 3  J  S n  3  J  S  -c).  calcd.  n  .  c  =  51.8 for  - 211 Preparation of methyl (Z)- and (E)-2 . 3-bis (trimethylstannyl')-8-bromo-2octenoate (141)  and (158)  Following general procedure 2, 8-bromo-2-octynoate  (95)  (931  to  a  stirred  solution  mixture was s t i r r e d at reflux for 16 h.  mg,  0.063  oil  with  petroleum ether-diethyl ether; 9:1)  (Z) isomer  1191, 52  (141).  771 cm" ; H nmr (400 MHz, CDCI3) 8: 0.24 1  Hz),  0.25  9H, -SnMe.3, J 2  3.40  (t,  2H,  BrCH -, 2  MHz, CDCI3) 6: -6.8 27.8  (t),  54 Hz,  J  S  Sn n  .  3  J  29.1 (t, S  n  .  c  J  S n  (t,  -C "  8  -  3  4  2  149.2  n  - 330 Hz).  546.9317;  found:  Exact  Mass  546.9321.  calcd.  (q,  33.6  (s),  for  S  n  .  ^sn-C (t),  40.6  164.8  (s),  S  n  •= 1 3  of  1707,  2  3H, -OMe);  Hz), -6.7  Hz), 32.5 ( t ) ,  - 66 Hz), 51.0 (q),  9H, -SnMe.3, J  2H, a l l y l i c protons, J  nmr (111.8 MHz, CDCI3) *: -36.05 (s, J S  g (83%)  S n  _H  - H = 54 Hz) , 1.34-1.49 (m, 4H),  J - 7.5 Hz), 3.70 (s,  (q, ^sn.c 3  S n  g,  and subjection of the  (s,  X  (s,  (30  This colorless o i l exhibited i r (film):  (quintet, 2H, J - 7.5 Hz), 2.34  1 1 9  gel  thus obtained to vacuum (0.05 Torr; 2 h ) , afforded 1.852  the  mmol).  Concentration, followed by  column chromatography of the resultant black o i l on s i l i c a elution  methyl  mg, 3.978 mmol) i n 55 mL of dry THF was  added hexamethylditin (3.978 mmol) and (PPl^^Pd (73 The  of  7.5  -  1.85 Hz),  C nmr (75.6  -  326  (t,  2  J  S n  Hz), -C  172.1  - 330 Hz), -36.95  C^H^O^BrS^  -  (s). (s,  (M+-CH3):  - 212 Following  general  procedure 3, the ester (141)  (120 mg, 0.21 mmol)  was converted into the bis(trimethylstannyl) ester (158), after s t i r r i n g at 86°C for 21 h.  Flash column chromatography of the pale yellow o i l on  s i l i c a gel (10 g,  elution  followed oil  by  petroleum  MHz,  2H,  oil  exhibited (s,  3  2  3  J_ _ S n  H  -  5  J - 7 Hz), 1.88  protons,  4  H z  ir  1  9H, -SnMe , ).  !-  (quintet,  J - 7 Hz), 3.41 (t,  342 Hz), 28.2  (t.  S  2  ^Sn-C " 54 Hz -  Sn n  .  (t),  29.6 3  2  3  3 2  (t,  J  S n  .  (quintet,  2H, J  -  7  -  H  5  6  H z  ).  °-  This  Hz),  2.48  (t,  J  S n  I - c ) > 51.8 Sn  2  (q, ^ S n - C -  3  4  3  Hz  (s),  s  172.1  6  9 H  allylic  3H, -OMe); ^Sn-C  33.5 ( t ) , (s),  183.9  S  n  - 558 Hz).  546.9317;  found:  Exact  Mass  S n  calcd.  for  C^^gC^^rS^  41.4 (s);  nmr (111.8 MHz, CDC1 ) 6: -50.47 (s, J - S n " 558 Hz), -51.49 3  -  (quintet,  > > " - ° (<1.  - c - 7.6 Hz), 32.6 ( t ) , (q), 144.1  ( .  5  2H, (s,  2  3  l  2H, J - 7 Hz), 1.49  2H, B r C H - , J = 7 Hz), 3.70  3  J  9:1)  (film): 1691, 1230, 772 cm" ; E nmr (400  C nmr (75.6 MHz, CDC1 ) 6: -6.5  1 1 9  ether;  d i s t i l l a t i o n (air-bath temperature 1 3 0 ° C / 0 . 0 5 Torr) of the  CDC1 ) 6: 0.15  -SnMe ,  -  ether-diethyl  thus obtained, afforded 106 mg (88%) of the (E) isomer (158).  colorless  1 3  with  (s,  (M -CH ): +  3  546.9321.  Preparation of methyl (Z)-2.3-bis(trimethylstannyl)-8-iodo-2-octenoate (142)  Following  general  procedure  2,  to  a  s t i r r e d solution of methyl  - 213 8-iodo-2-octynoate (99) (1.071 g, 3.825 mmol) i n 60 mL of THF was hexamethylditin  (3.825  mmol)  and  mixture was s t i r r e d at reflux column  chromatography  of  for  added  (PPh ) Pd (55 mg, 0.048 mmol). 3  6  h.  The  4  Concentration,  followed  by  the resultant black o i l on s i l i c a gel (40 g,  e l u t i o n with petroleum ether-diethyl ether; 97:3) and subjection of each of  the two o i l s thus obtained to vacuum (0.05 Torr; 2 h ) , afforded 1.54  g (76%) of the (Z) isomer (142) and 139 mg of methyl (99).  The colorless  oil  8-iodo-2-octynoate  (142) exhibited i r (film):  1707, 1191, 770  cm" ; ^-H nmr (400 MHz, CDC1 ) 6: 0.23 (s, 9H, -SnMe.3, J 1  2  3  0.24  (s, 9H, -SnMe ,  2  3  J  S n  _  H  -  5  5  H z  S n  ) . 1.32-1.45 (m, 4H), 1.82  2H, I C H C H - , J - 7 Hz), 2.30-2.37 (m, 2H, I ( C H ) C H - ) , 2  ICH -, 2  C  1 4  H  2 8  2  J O I  2  » 1 1 8  2  Sn  7 1 2 0  Hz), Sn  3.69  (s,  (M+-CH ):  3H,  -OMe).  592.9174;  3  -H "  found:  4  2  Exact  3  Hz  >>  (quintet,  3.18  Mass  5  (t,  2H,  calcd.  for  592.9170.  Preparation of compound (165)  C0 Et 2  <  SnMe  2  C0 Et 2  To a s t i r r e d solution of d i e t h y l 2,7-nonadiyndioate 0.1186  4  h.  (28 mg,  mmol) i n 5 mL of dry THF was added hexamethylditin (0.1186 mmol)  and (PPh3) Pd (5 mg, 0.004 mmol). 9  (112)  Concentration,  crude o i l on s i l i c a gel  followed (5  g,  The mixture was s t i r r e d at reflux for by  flash column chromatography of the  elution  with  petroleum  ether-diethyl  - 214 -  ether;  9:1)  and d i s t i l l a t i o n (air-bath temperature 115°C/0.05 Torr) of  the o i l thus obtained afforded 26 mg (56%) of colorless cm" ; 1  X  oil  exhibited  ir  (film):  1698,  H nmr (400 MHz, C D C 1 ) 8: 0.51 (s, (t,  -0CH CH , 2  25.7  J  3  (t),  172.8  -  (s).  found:  4H, allylic  7 Hz);  32.0 (t,  3  J  Exact  S  1611,  J - 7 Hz), 2 . 0 2 (quintet,  6 H , -OCH2CH3,  J - 8 Hz), 2.87 (t,  diene  1 3  .  n  c  C nmr  protons, (75.6  calcd.  for  -  8  (t), 2 2  Isn-H ~  >>  -7.8  129.7 4  (q),  (s),  (q, 14.4  169.5  (M+-CH3):  4H, (q),  (s),  386.0540;  (170)  Me Sn  CONMe  3  2  To a s t i r r e d s o l u t i o n of the appropriate acetylenic dry  THF was added hexamethylditin (1 equiv),  (0.0095-0.016 equiv). or  under  reflux  amide (1  afforded  equiv)  followed by Pd(PPh3)  4  The reaction mixture was s t i r r e d at room temperafor  26-72  h.  Concentration  of the mixture,  followed by column chromatography of the resultant crude o i l gel,  Hz  Preparation of ( E ) - N . N - d i m e t h v l - 2 . 3 - b i s ( t r i -  methylstannyl) -2-alkenamides  ture  0  386.0530.  General Procedure 4 :  in  6  4.17  Hz),  8:  C H 0 Sn 1 5  This  2 H , methylene protons,  CDCI3)  MHz,  - 46 Hz), 60.1  Mass  J  2  (165).  (br), 1 1 0 0 , 771  1216  6 H , -SnMe 2 .  3  1.28  the  on  silica  i n one case (Me-C»C-CONMe ) a mixture of the (Z) and (E) 2  isomers,  and i n a l l other cases studied,  gave exclusively  the (E) isomer  (170).  The (Z) isomer (167) was subjected to a vacuum of 0.05 Torr for  - 215 1 h at room temperature and the (E) isomers  were  distilled  (receiving  bulb cooled to - 1 0 ° C ) , affording i n a l l cases clear o i l s .  Preparation of (Z)- and (E)-N.N-dimethvl-2.3-bis(trimethylstannyl)-2butenamides (167)  Me Sn 3  Me Following  and (168)  W  SnMe  The  3  CONMe  167  general  hexamethylditin  CONMe  H  Me  2  procedure  methyl-2-butynamide (166) added  Me Sn  3  4,  to  168  by  flash  s i l i c a gel (25 g, afforded  two  3  a s t i r r e d solution of N,N-di-  (269 mg, 2.43 mmol) i n 20 mL of  (2.43  mmol)  dry  THF was  and (PPt^^Pd (27 mg, 0.023 mmol).  mixture was s t i r r e d at room temperature for  followed  SnMe  2  44  h.  Concentration,  column chromatography of the resultant crude o i l on elution  oils,  A  with and  petroleum  B.  ether-ethyl  Distillation  acetate;  (air-bath  1:1)  temperature  1 0 5 ° C / 0 . 1 Torr) of the o i l B provided 140 mg (13%) of  (E)-N,N-dimethyl-  2,3-bis(trimethylstannyl)-2-butenamide  subjection of the  oil  (168),  A to vacuum (0.1 Torr; 1.5 h) afforded  while  540  mg  dimethyl-2,3-bis(trimethylstannyl)-2-butenamide oil  (167)  MHz,  exhibited i r (film): 1620,  CDC1 )  -SnMe.3, J 2  4j  -Sn-H  6:  3  ~  S n  0.20  (s,  _ H - 54 Hz), 1.94 1  1  Hz  >>  2  -  c a l c d . for C H 4 0 N S n 11  2  2  9  1  <' s  1390,  (s,  3H, v i n y l  (M+-CH3):  2  9  The 1  -SnMe.3,  - -NMe)'  (167).  of  (Z)-N,Ncolorless  1160, 770 cm" ; H nmr  9H,  3 H  (50%)  2  5  425.9902;  J  S  n  .  H  X  - 54 Hz), 0.22  methyl,  3  J  S  n  (s. H , -NMe). 3  found:  .  H  -  (270  (s, 9H, 45  Hz,  Exact Mass  425.9909.  - 216 The c o l o r l e s s o i l (168) cm ; -1  0.25 c  X  exhibited i r (film): 1620,  H nmr (80 MHz, CDC1 ) 6:  0.12  3  (s,  46  9H, -SnMe.3, J  Hz,  ll 24 H  .  2  O N S n  4  J_sn-H "  1  1  n  -  2  9  2  425.9902;  (> s  6H  >  2j  (s,  5  3  775 Hz  3H, v i n y l methyl,  -NMe ).  3  >>  J  S n  -H  Exact Mass calcd. for  2  found:  1170,  9H, -SnMe.3, -Sn-H "  - 53 Hz), 2.05  H  )»  H z  2 (M+-CH3):  Preparation of  S  (s,  1390,  425.9906.  (E)-N.N-dimethyl-2.3-bis(trimethylstannyl)-2-pentenamide  (174)  Me Sn  CONMe  3  Et  SnMe  2  3  Following general procedure 4, to a s t i r r e d solution of N,N-dimethyl2-pentynamide  (171)  (565  mg, 4.42 mmol) i n 70 mL of dry THF was added  hexamethylditin (4.52 mmol) and (PPh ) Pd 3  mixture  was  stirred  at  reflux  (50  4  for 72 h.  mg,  0.045  mmol).  The  Concentration, followed by  column chromatography of the resultant black o i l on s i l i c a  gel  elution  distillation  with  petroleum  ether-diethyl  ether;  (air-bath temperature 1 0 5 - 1 0 8 ° C / 0 . 1 Torr) afforded  960 mg (48%) of the amide (174).  i r (film): (s,  9H,  1.00 (t, (s,  2j  1620,  -Sn-C  1385,  1160,  -SnMe.3, -Sn-H " 2j  5  3  the  and  oil  thus  2  1 3  2  65  Hz  ).  H z  0  2  <»  5  s  9 H  - -SnMe.3, -Sn-H " 2j  3  2  3  C nmr (75.4 MHz, CDCI3) 6: -8.01 (q, ^sn-c  -  3  J  S n  -c).  0.15  i  3  (q, ^ s n . c - 327 Hz), 14.6 (q, =  obtained,  775 cm" ; H nmr (80 MHz, CDC1 ) 6: 1  3  8  3  J  - ° (q).  S n  1  5  4  Hz  >>  Hz), "  3  1  9  - C - 8 Hz), 34.0 (q), 36.0 5  1  g,  This c o l o r l e s s o i l exhibited  3H, - C H C H , J - 7 Hz), 2.32 (q, 2H, - C H C H , J - 7  6H, -NMe );  -7.56  of  1:1)  (30  -  4  ( ). s  1 6  2 . 0 (s),  173.4  2.92 Hz  >. (t,  (s);  - 217 -  i i y  S n nmr (111.8 MHz, CDC1 ) 6:  -47.8 (s, J  3  J-Sn-Sn  ™  440.0058;  6  4  4  H z  )-  found:  Preparation of hexenamide  Exact  Mass  calcd.  S  n  .  = S  6  4  4  H z  n  for  C  H 1 2  26  ).  O N S n  -50.5 2  (s,  (M "-^): 4  440.0052.  (E)-N.N-dimethyl-2.3-bis(trimethylstannyl)-6-bromo-2-  (175)  Br  Following general procedure 4, to a s t i r r e d solution of N,N-dimethyl6-bromo-2-hexynamide  (172) (359 mg, 1.647 mmol) i n 25 mL of dry THF was  added hexamethylditin (1.647 mmol) and (PPl^^Pd (30 The  mixture was s t i r r e d at reflux for 26 h.  mg,  0.026  mmol).  Concentration, followed by  column chromatography of the resultant brown o i l on s i l i c a  gel  elution  distillation  with  petroleum  ether-ethyl  acetate;  1:1)  and  ( a i r - b a t h temperature 1 2 5 ° C / 0 . 1 Torr) of the o i l thus obtained, 679  mg  1619,  (75%) of the amide (175).  -SnMe.3,  2j  (quintet,  -Sn-H 2H,  BrCH CH CH -), 2  Hz).  2  2  "  5  3  Hz  X  > •  °-  BrCH CH CH -, 2  2.91  2  2  6  J  2  <> s  -  9H  >  2  3  533.9304.  5:  0.16  (s,  9H,  2j  Hz),  2.39-2.52  (m,  2H,  -42 (t, 2H, BrCH CH CH -, J - 7.5  Exact Mass c a l c d . for C H 7 0 N B r S n  2  81  2  afforded  -SnMe.3, -Sn-H " 55 Hz), 1.91  7.5  (s, 6H, -NMe ), 13  g,  This yellow o i l exhibited i r (film):  1491, 1162, 769 cm" ; H nmr (400 MHz, CDCI3) 1  (20  2  (M" "-^): 533.9300; 1  2  2  found:  - 218 Preparation of (E)-N.N-dimethyl-2.3-bis(trimethylstannyl)-6-tert-butyldimethylsiloxy-2-hexenamide  (176)  Me Sn  CONMe  3  2  t  Bu Me SiO 2  Following  general  procedure  4,  to  a s t i r r e d solution of N,N-di-  methyl-6-tert-butyldimethylsiloxy-2-hexynamide in  (173)  (159 mg, 0.59 mmol)  20 mL of dry THF was added hexamethylditin (0.59 mmol) and (PPl^^Pd  (10 mg, 0.008 mmol). Concentration,  The mixture  was  and  at  reflux  with  petroleum  ether-ethyl  exhibited  ir  MHz, CDC1 ) 8: 0.06 3  54  Hz), 0.25  1.57  (s,  (quintet,  (s,  (s,  6H, ButMe^SiO-), 0.16  9H, -SnMe.3, ^Sn-H 2  =  5  2  2  2.92  2  (s,  c  19 42°2 H  (t),  (t),  1 3  2  2  7  )>  ' -  34.2  (q),  Hz  152.5  N S i S n  2  > •  0  9  <>  1  3H, -NMe), 2.94  t  3  Hz  s  2  2H, Bu Me SiOCH2CH CH2-, J - 6.0 Hz);  63.0  4  9H, -SnMe.3,  t  2  This colorless 1  2H, Bu Me Si0CH CH CH2-, J = 6 . 0 H z ) ,  2  (q), 33.5  acetate;  840, 780 c m ' ; ^-H nmr (400  t  -  h.  (film): 1620, 1380, 1100,  Bu Me SiOCH2CH CH2-),  (^ISn-C  48  d i s t i l l a t i o n (air-bath temperature 1 7 0 ° C / 0 . 1 Torr) of the o i l  thus obtained, afforded 222 mg (63%) of the amide (176). oil  for  followed by column chromatography of the resultant crude  o i l on s i l i c a gel (20 g, e l u t i o n 4:1)  stirred  7  (s),  6  <<1. ^iSn-C "  3  2  160.5  (s),  ^Sn-H  8  Hz  173.7  > • ' 5  3  J  S  n  .  (s).  C  =  - £11^62810-),  2.33-2.42  (m,  2H,  3H, -NMe), 3.64  C nmr (75.4 MHz, CDCI3) 6:  38.3 (q), 40.3 (t,  (M -CH ): 584.1029; +  3  (s,  9 H  2  •  7  - 63  1  8  •  Hz  <> •  3  s  -  2  2  (t, -8.0  5  -  9  i n-c)• S  Exact Mass c a l c d . for  found: 584.1031.  - 219 -  V.  Chemistry o f a l k y l ( Z ) - and ( E ) - 2 , 3 - b i s ( t r i m e t h y l s t a n n y l ) - 2 alkenoates  General Procedure 5:  Transmetalation of a l k v l ( Z ) - and  (E)-2.3-bis(tri-  methylstannyl') -2-alkenoates and reaction of the resultant with  intermediates  electrophiles  To a cold ( - 9 8 ° C ) ,  s t i r r e d solution of the appropriate a l k y l ( Z ) - or  (E)-2,3-bis(trimethylstannyl)-2-alkenoate (1 (-20  equiv)  in  anhydrous THF  mL per mmol) was added methyllithium (1.1-1.2 equiv) as a solution  i n ether. 10-35  The r e s u l t i n g dark yellow solution was s t i r r e d at  min.  The  appropriate  electrophile  for  30  min  and  at  -78°C for 45 min-2.5 h.  stirred  was allowed to warm to room temperature.  magnesium  sulfate,  and concentrated.  either d i s t i l l e d d i r e c t l y or was flash  the  The organic layer was  washed three times with saturated aqueous ammonium chloride anhydrous  at  Saturated aqueous  ammonium chloride (2 mL/mmol) and ether (20 mL/mmol) were added and mixture  for  (3-20 equiv) which had been  passed through basic alumina, was added and the mixture was -98°C  -98°C  dried  over  The r e s u l t i n g o i l was  chromatographed  on  silica  gel  (elution with petroleum ether-diethyl ether or petroleum ether-dichloromethane) p r i o r to d i s t i l l a t i o n .  - 220 Preparation of ethvl butenoate  (Z)-2-(3-chloropropyl)-3-trimethylstannvl-2-  (180)  Cl Following general procedure 5, to a cold ( - 9 8 ° C ) , of  ethyl  (E)-2,3-bis(trimethylstannyl)-2-butenoate  mmol) i n 6 mL of dry THF was added a solution mmol) i n ether.  of  stirred (77)  solution  (288 mg,  methyllithium  0.515 (0.593  After the mixture had been s t i r r e d at -98°C for 10 min,  l-chloro-3-iodopropane (-20 mmol) was added and the solution was s t i r r e d at  -98°C for 30 min and at -78°C for 1.5 h.  Normal workup, followed by  flash column chromatography of the residual o i l on elution  with  (air-bath  petroleum  temperature,  ether-diethyl 85°C/0.05  ether;  Torr)  of  afforded 98 mg (54%) of the chloride (180) polymeric gum). cm- ; 1  i  1.31  H  (t,  Hz),  3H, -OCH CH , J - 7 Hz), 1.89 2  2  (s,  3H,  vinyl  methyl,  2H, -0CH CH , J - 7 Hz);  44.8  1 3  3  359 Hz), 14.2 (t),  (t,  (q), 22.0 (q,  (t),  60.9 ( t ) ,  c a l c d . for C H O 1 1  2 0  3 5 2  3  J  S n  oil  thus  obtained,  S  n  .  137.6  5  5  -H  774  Hz  > •  2H, C1CH CH CH -, J = 8 2  "  5  1  Hz  >•  2  2  •  2  ( '  6 0  C  2H  2H, C1CH CH CH -, J - 8 Hz), 4.21 2  2  C  "  4  4  (s),  C l S n (M+'C^):  Hz  >-  164.5  2  5  -  ( ^Sn-C "  2  3  (s),  339.0174;  168.9  > (q,  2  (q, ^ S n - C "  3  J  1263,  3  C nmr (75.6 MHz, CDC1 ) 6: -6.7 2  g,  and d i s t i l l a t i o n  9H, -SnMe , "SIsn-H "  (quintet,  3  2  2  the  (15  (the s t i l l pot contained some  (s,  3  C1CH CH CH -, J - 8 Hz), 3.53 2  17:1)  gel  This colorless o i l exhibited i r (film): 1693,  nmr (400 MHz, CDC1 ) 6: 0.13  2.10  silica  4  (s).  1  Hz  >•  3  2  -  2  Exact Mass  found: 339.0167.  - 221 Preparation of ethyl  (E)-2-trimethvlsilvl-3-trimethylstannvl-2-butenbate  (181)  Me Sn  C0 Et  Me  SiMe  3  Following  general  2  3  procedure 5, to a cold ( - 9 8 ° C ) ,  of ethyl (E)-2,3-bis(trimethylstannyl)-2-butenoate mmol)  in  (77) (178  mmol) i n ether.  (-10 mmol) was added and the solution was s t i r r e d  at -98°C for 30 min and at -78°C for 2 h. distillation  (air-bath  Normal  workup,  ir  (film): 1695,  9H, -SnMe , 3  -  J  S n  -H ~  5  -OCH CH ,  4.12  (q, 2H, -OCH CH , J - 7 Hz).  3  J  2  1240,  3H,  2  2  (M -CH ): +  3  335.0489;  7 Hz), 2.22 3  followed  by  temperature 8 0 ° C / 0 . 0 5 Torr) of the residual o i l  afforded 99 mg (70%) of the stannyl silane (181).  (s,  0.402  After the mixture had been s t i r r e d at -98°C for 10 min,  chlorotrimethylsilane  5: 0.15  mg,  mL of dry THF was added a solution of methyllithium (0.433  6  exhibited  s t i r r e d solution  This  850, 775 c m ; ^ - 1  3  Hz  >> ° -  (s,  2  5  <> s  9 H  -  colorless  nmr (80 MHz, CDC1 ) 3  - S i M e ) , 1.30 3  calcd.  (t,  3  3H, v i n y l methyl, J_sn-H ~  Exact Mass  oil  for  5  1  Hz  >>  C H 0 SiSn n  2 3  2  found: 335.0487.  Preparation of ethvl (Z)-2-(2-methyl-2-propenvl)-3-trimethvlstannvl-2butenoate  (182)  - 222 Following  general  procedure 5, to a cold ( - 9 8 ° C ) ,  of ethyl (E)-2,3-bis(trimethylstannyl)-2-butenoate mmol)  in  5  column  chromatography  of  Normal  ether-dichloromethane;  (air-bath  ~80°C/0.05  temperature  Torr)  (s, 9H, -SnMe.3, 3H,  vinyl  2  I  S n  44:1)  of  afforded 58 mg (69%) of the alkene (182). 1680,  workup,  followed  by  the residual o i l on s i l i c a gel (10 g,  e l u t i o n with petroleum  (s,  0.254  (-5 mmol) was added and the solution was s t i r r e d  at -98°C for 30 min and at -78°C for 2 h.  (film):  mg,  After the mixture had been s t i r r e d at -98°C for 10 min,  3-iodo-2-methylpropene  ir  (77) (112  mL of dry THF was added a solution of methyllithium (0.319  mmol) i n ether.  flash  s t i r r e d solution  the  and  oil  distillation  thus  obtained,  This colorless o i l  exhibited  1580, 1280, 770 cm" ; H nmr (80 MHz, CDC1 ) 6: 0.11 1  X  3  -H "  methyl),  5  4  Hz  >>  2.01  1  -  2  3  3H  (s,  >  -OCH CH , J - 7 Hz), 2  1.62  3  3H, v i n y l methyl, J_s -H " 3  4  8  Hz  n  >»  3.03-3.18 (br s, 2H, b i s - a l l y l i c protons), 4.13 (q, 2H, -0CH CH , J = 7 2  Hz),  4.41-4.56  proton).  (br  s,  3  IH, v i n y l proton), 4.58-4.65 (br s, IH, v i n y l  Exact Mass calcd. for C H 0 S n (M -CH ): +  1 2  2 1  2  3  317.0564;  found:  317.0559.  Preparation of ethyl butenoate (183)  (Z)-2-(4-iodo-4-pentenyl)-3-trimethylstannyl-2-  - 223 Following  general  procedure 5, to a cold ( - 9 8 ° C ) ,  of ethyl (E)-2,3-bis(trimethylstannyl)-2-butenoate mmol)  in  5  (-40  column  e l u t i o n with  chromatography petroleum  of  1695,  120°C/0.05  J  2  3  S  (quintet, 3j  -Sn-H  =  .  Torr)  5  3  2  H z  J  1  1.31  -  -  4  2  7  2  ( ' c  2  4H  >  Hz),  thus  obtained,  oil  exhibited  This colorless  3H,  J  -OCH CH , 2  - 8 Hz), 2.07  J  3  (s,  -  7  2  2  2  (s, 9H,  Hz),  1.75  3H, v i n y l methyl,  2  (q,  2H,  (IH, v i n y l proton, J - 1.5 Hz), 6.04 (IH,  Exact Mass calcd. for C H 0 I S n 1 3  2 2  2  (M -CH ): +  found: 456.9685.  Preparation of ethyl butenoate  oil  -CH CH CH CICH , J = 8 Hz), 4.19  5.66  v i n y l proton, J •= 1.5 Hz). 456.9689;  (t, 2  by  distillation  3  2  2  the  and  X  -CH CH CH CICH ,  >'  of  97:3)  775 cm" ; H nmr (270 MHz, CDC1 ) 5: 0.13  = 54 Hz),  H  2H,  -OCH CH , 2  n  1220,  Normal workup, followed  ether;  afforded 41 mg (42%) of the alkene (183).  -SnMe ,  0.209  the residual o i l on s i l i c a gel (10 g,  ether-diethyl  temperature  (film):  mg,  mmol) was added and the solution was s t i r r e d  at -98°C for 30 min and at -78°C for 2.5 h.  ir  (92  After the mixture had been s t i r r e d at -98°C for 30 min,  2,5-diiodo-l-pentene  (air-bath  (77)  mL of dry THF was added a solution of methyllithium (0.262  mmol) i n ether.  flash  s t i r r e d solution  (184)  (Z)-2-(3-methyl-2-butenvl)-3-trimethylstannyl-2-  3  - 224 Following  general  procedure 5, to a cold ( - 9 8 ° C ) , s t i r r e d solution  of ethyl (E)-2,3-bis(trimethylstannyl)-2-butenoate mmol)  in  5  (-5 mmol) was added and the  s o l u t i o n was s t i r r e d at -98°C for 30 min and at -78°C for 3 followed  oil  exhibited  of  3  J  -  2  3  7  Hz),  the  alkene  (184).  This  1  3  2  Normal  i r (film): 1680, 1580, 1270, 770 cm" ; E nmr  (400 MHz, CDC1 ) 8: 0.13 (s, 9H, -SnMe , -0CH CH ,  h.  by d i s t i l l a t i o n (air-bath temperature 8 0 ° C / 0 . 0 5 Torr)  of the r e s i d u a l o i l afforded 58 mg (66%) colorless  0.254  After the mixture had been s t i r r e d at -98°C for 30 min,  d i s t i l l e d 1-bromo-3-methyl-2-butene  workup,  mg,  mL of dry THF was added a solution of methyllithium (0.317  mmol) i n ether. freshly  (77) (112  J n-H "  5  5  Hz  S  > > 1  3  0  l  ->  (  t  3H  >  1.69 (s, 3H, v i n y l methyl), 1.71 (s, 3H, v i n y l  methyl), 2.08 (s, 3H, v i n y l methyl,  3  J_s -H n  "  5  1  Hz  > •  3  -  1  4  ( d  2H  >  b i s - a l l y l i c protons, J - 7.5 Hz), 4.19 (q, 2H, -OCH CH , J - 7 Hz), 5.00 2  (t, IH, v i n y l proton, J = 7.5 Hz). (M -CH ): +  3  331.0720;  Preparation  of  Exact  Mass  3  calcd.  for  C^ H 0 Sn 3  23  2  found: 331.0724.  ethvl  (Z)-2-(3-trimethvlsilvl-2-propvnyl)-3-trimethyl-  stannyl -2-butenoate (185)  Following general procedure 5, to a cold ( - 9 8 ° C ) , of  ethyl  (E)-2,3-bis(trimethylstannyl)-2-butenoate  mmol) i n 5 mL of dry THF was added a  solution  of  stirred  solution  (77) (88 mg, 0.200 methyllithium  (0.25  - 225 mmol) i n ether.  After the mixture had been s t i r r e d at -98°C for 30 min,  3-bromo-l-trimethylsilylpropyne was  (-4.0  mmol) was added and  s t i r r e d at -98°C for 30 min and at -78°C for 2.5 h.  the  solution  Normal workup,  followed by column chromatography of the residual o i l on s i l i c a g,  e l u t i o n with petroleum ether-dichloromethane;  97:3)  gel  and d i s t i l l a t i o n  (air-bath temperature 1 0 5 ° C / 0 . 5 Torr) of the o i l thus obtained, 30  mg  (40%)  of  the  exhibited i r ( f i l m ) : 5:  CDC1 ) 3  1.31  (t,  Hz),  0.14  trimethylsilylalkyne  2160,  (s,  1685,  1270,  9H, - S i M e ) , 0.15 3  3H, -OCH CH , J - 7 Hz), 2.14  3.36  2  (s,  3  2H, a l l y l i c protons),  840, (s, (s, 4.14  (185). 765 c m ; - 1  2 5  afforded  This c o l o r l e s s o i l X  H nmr  9H, -SnMe.3, J 2  S n  (400  -H ~  3H, v i n y l methyl,  3  J  S n  5  MHz, 5  H z  ) •  -H "  5  0  (q, 2H, -OCH CH , J = 7 Hz).  Exact Mass calcd. for C H 0 S i S n (M+-CH3): 373.0640; 1 4  (5  2  2  3  found: 373.0643.  Preparation of methyl  (Z)-2-methyl-3-trimethvlstannvl-5-(2-cvclo-  pentenvl)-2-pentenoate  (186)  Following general procedure 5, to a cold ( - 9 8 ° C ) ,  stirred  solution  of methyl (E)-2,3-bis(trimethylstannyl)-5-(2-cyclopentenyl)-2-pentenoate (153)  (75.7 mg, 0.149 mmol) i n 5 mL of dry THF was added a  methyllithium (0.178 mmo 1) i n ether. at -98°C for 15 min, iodomethane  (-3.0  solution  of  After the mixture had been s t i r r e d mmol) was added and the  solution  - 226 was  stirred  at  -98°C for 30 min and at -78°C for 1 h.  Normal workup,  followed by column chromatography of the residual o i l on s i l i c a gel g,  elution  with  (10  petroleum ether-diethyl ether; 99:1) and d i s t i l l a t i o n  ( a i r - b a t h temperature 1 0 0 ° C / 0 . 5 Torr) of the o i l thus obtained, afforded 39 mg (72%) of the ester (186). 1697, 2j  -Sn-H  1280, 770 cm" ; H nmr (400 MHz, CDCI3) 6: 0.13 1  -  5  5  H z  v i n y l methyl,  4  J  >. S n  (t, 2H, a l l y l i c -OMe). c  S n  (s,  1  1-17-1.38  9H,  -SnMe , 3  (m, 2H), 1.41-1.51 (m, IH) , 1.94 (s, 3H,  - H - 9 Hz), 2.02-2.12 (m, IH), 2.23-2.42 (m, 2H), 2.46 protons, J = 7 Hz),  5.64-5.78  14 23°2 H  This colorless o i l exhibited i r (film):  (m,  (M -CH ): +  3  2H, v i n y l  343.0720;  Preparation of methvl  2.62-2.73  protons).  (m,  IH), 3.74  Exact  Mass  (s, 3H,  calcd.  for  found: 343.0723.  (Z)-2-(2-methvl-2-propenyl)-3-trimethvlstannvl-  5-(2-cvclopentenyl)-2-pentenoate (187)  C0 Me  Me Sn 3  Following of methyl (153)  (140  general  2  procedure 5, to a cold ( - 9 8 ° C ) ,  s t i r r e d solution  (E)-2,3-bis(trimethylstannyl)-5-(2-cyclopentenyl)-2-pentenoate mg,  0.275 mmol) i n 5 mL of dry THF was added a s o l u t i o n of  methyllithium (0.330 mmol) i n ether.  After the mixture had been s t i r r e d  at -98°C for 15 min, 3-iodo-2-methylpropene  (-30 mmol) was added and the  s o l u t i o n was s t i r r e d at -98°C for 35 min and at -78°C for 1.5 h.  Normal  - 227 workup,  followed by d i s t i l l a t i o n (air-bath temperature 1 2 5 ° C / 0 . 0 5 Torr)  of the r e s i d u a l o i l afforded 75 mg (68%) colorless  oil  exhibited  alkene  (187). - 1  3  1.76  the  This  i r (film): 1700, 1290, 1210, 780 c m ; H nmr  (400 MHz, CDC1 ) 6: 0.14 (s, 9H, -SnMe , 3H),  of  3  2  J  S n  -H °  5  4  Hz  )>  X  1-17-1.49  (m,  (s, 3H, v i n y l methyl), 2.00-2.10 (m, IH), 2.21-2.45 (m, 4H),  2.61-2.71 (m, IH), 3.11 (s,  2H, b i s - a l l y l i c  protons),  3.70  (s,  3H,  -OMe), 4.53 (s, IH, v i n y l proton), 4.71 (s, IH, v i n y l proton), 5.64-5.77 (m,  2H, v i n y l protons).  383.1033;  Exact  Mass  calcd.  for  C H270 Sn 17  2  (M -CH ): +  3  found: 383.1030.  Preparation of methyl (Z)-2-(3-methyl-2-butenvl)- 3-trimethylstannyl5-(2-cvclopentenyl)-2-pentenoate (188)  Following of methyl (153)  (151  general  procedure 5, to a cold ( - 9 8 ° C ) ,  (E)-2,3-bis(trimethylstannyl)-5-(2-cyclopentenyl)-2-pentenoate mg,  0.297 mmol) i n 6 mL of dry THF was added a solution of  methyllithium (0.348 mmol) i n ether. at  -98°C  s t i r r e d solution  After the mixture had been s t i r r e d  for 10 min, freshly d i s t i l l e d 1-bromo-3-methyl-2-butene  (-5.0  mmol) was added and the solution was s t i r r e d at -98°C for 30 min and at -78°C  for  1.5  h.  Normal  workup, followed by d i s t i l l a t i o n (air-bath  temperature 1 1 5 - 1 2 0 ° C / 0 . 0 5 Torr) of the  residual  oil  afforded  87 mg  - 228 (71%) of the alkene  (188).  This colorless o i l exhibited i r (film):  1698, 1580, 1285, 1230, 775 cm" ; H nmr (AOO MHz, CDC1 ) 6: 1  X  3  9H,  -SnMe.3, J 2  S n  .  H  - 55 Hz), 1.17-1.40 (m, 2H), 1.40-1.51 (m, IH), 1.59  (s, 3H, vinyl methyl), 1.61 (s, 3H, vinyl methyl), 2.22-2.57  0.13 (s,  2.01-2.12  (m, IH),  (m, 4H), 2.64-2.74 (m, IH), 3.11 (d, 2H, b i s - a l l y l i c protons,  J - 7 Hz), 3.73 (s, 3H, -OMe), 4.99 (broad t, IH, vinyl proton, Hz), 5.66-5.78 (m, 2H, vinyl protons).  J - 7  Exact Mass calcd. for C ^ g ^ ^ S n  (M+-CH3): 397.1190; found: 397.1188.  Preparation of ethyl  (Z)-2-(2-methvl-2-propenvl)-3-trimethylstannyl-4-  tert-butyldimethylsiloxy-2-butenoate (189)  Following general procedure 5, to a cold (-98°C), of  ethyl  stirred  solution  (E)-2,3-bis(trimethylstannyl)-4-tert-butyldimethylsiloxy-2-  butenoate (152) (386 mg, 0.675 mmol) i n 15 mL of dry THF was solution  of methyllithium (0.843 mmol) i n ether.  After the mixture had  been stirred at -98°C for 25 min, 3-iodo-2-methylpropene (-7 added  135 C/0.1 (189). 845,  mmol) was  and the solution was stirred at -98°C for 30 min and at -78°C for  1.5 h. Normal workup, followed by d i s t i l l a t i o n o  added a  (air-bath temperature  Torr) of the residual o i l afforded 240 mg (74%) of the alkene  This colorless o i l exhibited i r (film): 1700, 1645, 1270, 1050, 780 cm" ; H nmr (400 MHz, 1  X  CDCI3)  S: 0.04 (s, 6H, B^M^Si-), 0.16  - 229 -  (s, 9H, -SnMe ,  J  2  3  -OCH CH , 2  J  3  -  S  n  .  7  - 55 Hz), 0.89 (s, 9H, B i ^ M e ^ i - ) , 1.27  H  Hz),  1.74  (s,  3H,  vinyl  methyl),  b i s - a l l y l i c protons), 4.17 (q, 2H, -OCH CH , J - 7 2  -CH OSiBu Me , t  2  2  3  J_Sn-H "  v i n y l proton) .  4  8  Hz  > •  4  -  5  6  3  (t,  3.10  Hz),  3H,  (s, 2H,  4.38  (s,  2H,  (s, IH, v i n y l proton), 4.73 (s, IH,  Exact Mass c a l c d . for C H 0 S i S n l g  3 5  3  (M+-CH;}):  447.1378;  found: 447.1379.  Preparation of ethvl  (Z)-2-methyl-3-trimethvlstannvl-4-tert-butvl-  dimethylsiloxv-2-butenoate  Following of  ethyl  general  (190)  procedure 5, to a cold ( - 9 8 ° C ) , s t i r r e d solution  (E)-2.3-bis(trimethylstannyl)-4-tert-butvldimethvlsiloxv  butenoate  (152)  (93  mg,  0.1625  mmol) i n 5 mL of dry THF was added a  s o l u t i o n of methyllithium (0.1788 mmol) i n ether. been  stirred  After the mixture had  at -98°C for 15 min, iodomethane (-20 mmol) was added and  the s o l u t i o n was s t i r r e d at -98°C for 30 min and at Normal  2-  -78"C for  1.5  h.  workup, followed by d i s t i l l a t i o n (air-bath temperature 9 5 - 1 0 0 ° C /  0.1 Torr) of the residual o i l afforded 51 mg (74%) of the alkene  (190).  This c o l o r l e s s o i l exhibited i r (film): 1698, 1640, 1270, 1050, 840, 770 cm" ; 1  l  tt nmr (270 MHz, CDC1 ) 6: 0.04 (s, 6H, B ^ M e ^ S i - ) , 0.13 3  -SnMe , 3  2  J  S n  -H ~  5  6  Hz  >> ° -  8  8  <» s  9H  (s,  9H,  > B u M e S i - ) , 1.28 (t, 3H, -OCH CH , t  2  2  3  J - 7 Hz), 1.94 (s, 3H, v i n y l methyl), 4.17 (q, 2H, -OCH CH , J - 7 Hz), 2  3  - 230 -  4.41  (s,  CDC1 ) 5: 3  (s),  26.0  169.5  2H,  allylic  -6.0  (q, ^ s n . c - 365 Hz), -5.2  (q),  (s).  61.0  Exact  (t), Mass  protons,  64.3  ^Isn-H  (t,  calcd.  2  J  "  -C "  S n  for  4  8  H z  >:  c  (q), 14.3 2  7  H z  >.  1  3  3 1  m  (q), 4  C H 0 SiSn 1 5  n  -  5  <  r  7 5  14.6  <) > i s  6  m z  (q), 6  (M+-CH ):  3  -  -  3  1  >  18.3 <) > s  407.1065;  3  found: 407.1062.  Preparation of ethyl  (Z)-2-(3-methyl-2-butenyl)-3-trimethylstannyl-  4-tert-butyldimethylsiloxy-2-butenoate  C0 Et  Me Sn  2  3  BJ  Following of ethyl noate  (191)  Me SiO 2  general  procedure 5, to a cold ( - 9 8 ° C ) ,  (E)-2,3-bis(trimethylstannyl)-4-tert-butyldimethylsiloxy-2-bute-  (152)  (813  mg,  1.421  mmol)  in  40  mL of dry THF was added a  s o l u t i o n of methyllithium (1.70 mmol) i n ether. been  After the  mmol) was added and the solution was s t i r r e d at  min and at -78°C for 1.5 h.  (81%)  1698, (s,  had  of the alkene (191).  1640, 6H,  1280,  2  (t,  afforded  This c o l o r l e s s o i l exhibited i r  840, 780 cm" ; H nmr (400 MHz, CDC1 )  B ^ M e ^ S i - ) , 0.15  B u M e S i - ) , 1.27 t  1080,  -98°C  1  9H, -SnMe ,  2  3  3H, -OCH CH , 2  3  J  -  7  J  S n  -H "  Hz),  5  6  H z  1.68  ) • °(s,  9  0  546  (film):  5:  X  3  (s,  for  Normal workup, followed by d i s t i l l a t i o n  ( a i r - b a t h temperature 1 1 0 ° C / 0 . 1 Torr) of the r e s i d u a l o i l mg  mixture  s t i r r e d at -98°C for 25 min, freshly d i s t i l l e d l-bromo-3-methyl-2-  butene (-5.0 30  s t i r r e d solution  <>  6H,  s  0.05 9H  >  vinyl  - 231 methyls),  3.10  (d,  2H,  bis-allylic  -OCH CH , J - 7 Hz), 4.43 2  (broad  t,  IH,  vinyl  3 7  propenoate  t  2  J  461.1534;  3  Preparation of methyl  2H, -CH OSiBu Me ,  proton,  C H 0 S i S n (M+'CH^: 1 9  (s,  3  protons, J - 7 Hz), 4.19  -  2  7  Hz).  3  J.Sn-H  =  Exact  4  8  Hz  Mass  (q, 2H,  )>  4  c a l c d . for  (192)  C0 Me 2  Following general procedure 5, to a cold ( - 9 8 ° C ) ,  stirred  solution  of methyl (E)-2,3-bis(trimethylstannyl)-3-cyclopropyl-2-propenoate (43.3 mg, 0.09 mmol) In 5 mL of dry THF was added a solution of (0.140  mmol)  i n ether.  at  -98°C  for  30  min and at -78°C for 1.5 h.  followed by d i s t i l l a t i o n (air-bath temperature  exhibited i r (film): 1695,  5:  0.13  (m,  2H), 1.44-1.54 (m, IH), 2.06  -OMe). 289.0240.  80°C/0.1  o i l afforded 21.6 mg (79%) of the ester (192).  oil  (s,  Exact  9H, -SnMe , 3  Mass  2  J  S n  1270, _  H  (149)  methyl-  After the mixture had been s t i r r e d at  -98°C for 15 min, iodomethane (-2 mmol) was added and the  residual  7  (Z)-2-methvl-3-trimethylstannyl-3-cvclopropvl-2-  3  stirred  9  found: 461.1536.  Me Sn  lithium  -  770 c m ; - 1  X  H nmr (270  solution  was  Normal workup, Torr)  of  the  This colorless MHz,  CDC1 ) 3  - 54 Hz), 0.32-0.41 (m, 2H), 0.83-0.94 (s,  3H, v i n y l  methyl),  c a l c d . for C H O S n (M+-CH5): 1 0  1 7  2  3.70  289.0250;  (s,  3H,  found:  - 232 Preparation of methyl  (Z)-2-(2-methyl-2-propenvl)-3-trimethvlstannvl-  3-cvclopropvl-2-propenoate (193)  Following general procedure 5, to a cold ( - 9 8 ° C ) ,  stirred  solution  of methyl (E)-2,3-bis(trimethylstannyl)-3-cyclopropyl-2-propenoate (354 mg, 0.779 mmol) i n 8 mL of dry THF was added a solution of lithium  (0.896  mmol)  i n ether.  (149)  methyl-  After the mixture had been s t i r r e d at  -98°C for 10 min, 3-iodo-2-methylpropene  (-7 mmol)  was  added  and the  solution was s t i r r e d at -98"C for 30 min and at -78°C for 1.5 h.  Normal  workup, followed by d i s t i l l a t i o n (air-bath temperature 9 5 ° C / 0 . 1 Torr) of the  residual  oil  afforded  204  mg  (76%)  of the alkene (193).  c o l o r l e s s o i l exhibited i r (film): 1700, 1290, 1205, 780 cm (270 2H), 3.28  MHz, CDC1 ) 6: 0.15 (s, 9H, -SnMe.3, J 2  3  (s,  13 21°2 H  n  .  2H, b i s - a l l y l i c  S n  (M" "-^): 1  protons),  IH, v i n y l  329.0564;  ;  X  H nmr  - 56 Hz), 0.40-0.48 (m,  H  0.80-0.90 (m, 2H), 1.46-1.58 (m, IH), 1.75 (s, 3H, v i n y l  v i n y l proton), 4.68 (s, c  S  _ 1  This  methyl),  3.67 (s, 3H, -OMe), 4.46 (s, IH,  proton).  Exact  found: 329.0566.  Mass  calcd.  for  - 233 Preparation of methyl pentenoate  (Z)-2-(2-propenvl)-3-trimethylstannyl-2-  (179)  Following  general  procedure 5, to a cold ( - 9 8 ° C ) , s t i r r e d solution  of methyl (Z)-2,3-bis(trimethylstannyl)-2-pentenoate mmol)  in  3-iodopropene  8.46  After the mixture had been s t i r r e d at -98°C for 15 min, (12.69  mmol)  was  added and the solution was s t i r r e d at  -98°C for 30 min and at -78°C for 45 min. distillation  (air-bath  temperature  afforded 2.295 g (85%) of the  MHz, CDC1 ) 6: 0.15  (s,  3  Normal  alkene  (179).  1284,  9H, -SnMe.3, J.Sn-H 2  - C H C H , J - 7.5 Hz), 2.45 3  workup,  followed  This  1213, =  5  4  2  colorless 1  H z  ) > °J  3  3  S  X  9  n  Hz),  5.84  B  1 Hz), 4.98  (ddt, IH, H , J = 17, 10, 6 Hz). c  (>  3  .  3.19 (dt, 2H, b i s - a l l y l i c protons, J » 6, 1.5 Hz), 3.73 (s, (ddt, IH, H , J - 10, 1.5,  oil  773 cm" ; H nmr (270  (q, 2H, - C H C H , J •= 7.5 Hz,  4.96  by  8 2 - 8 6 ° C / 0 . 0 5 Torr) of the residual  exhibited i r (film): 3080, 1700, 1639,  2  (3.47 g,  120 mL of dry THF was added a solution of methyllithium (9.73  mmol) i n ether.  oil  (125)  t  H  3 H  '  - 48 Hz),  3H,  -OMe),  (ddt, IH, H , J - 17, 1.5, A  In a nOe difference  1  experi-  ment, i r r a d i a t i o n of the singlet at 6 3.73 (-OMe), caused enhancement of the s i n g l e t at 6 0.15 (-CH CH ) 2  3  caused  signal  (-CH CH ) and S 0.15 2  0.15  3  (-SnMe ) 3  (-SnMe.3).  enhancement  (-SnMe.3).  caused  I r r a d i a t i o n of the  signal  at  6  signal  at  6  2.45  3.19 (-CH CH=CH ), 6 0.93 2  2  F i n a l l y , i r r a d i a t i o n of the singlet at 6 enhancement  at 6 0.93  (-CH CH3), S 2.45 2  - 234 and  (-CH2CH3),  (M+-CH3):  6  3.73  303.0407;  (-OMe).  Exact  Mass  calcd.  for  C H 0 Sn 1 1  1 9  2  found: 303.0406.  Preparation of methyl (Z)-4-methvl-l-(2-propenyl)-3-trimethvlstannvl2-pentenoate  (194)  Following  general  procedure 5, to a cold ( - 9 8 ° C ) , s t i r r e d solution  of methyl (Z)-2,3-bis(trimethylstannyl)-4-methyl-pentenoate g,  (126)  (1.608  3.52 mmol) i n 70 mL of dry THF was added a solution of methyllithium  (3.88 mmol) i n ether. 10  min,  After the mixture had been s t i r r e d at  3-iodopropene  column  e l u t i o n with  for  (10 mmol) was added and the solution was s t i r r e d  at -98°C for 30 min and at -78°C for 45 min. flash  -78°C  chromatography petroleum  of  Normal workup, followed by  the residual o i l on s i l i c a gel (45 g,  ether-diethyl  ether;  49:1)  and  distillation  (air-bath temperature 7 0 ° C / 0 . 0 5 Torr) of the residual o i l thus obtained, afforded 849 mg (73%) of the ester (194). ir  (film):  6: 0.20  CDCI3)  J  -  3081,  7  Hz),  (s, 3.07  1703,  1639,  1277,  9H, -SnMe , J_s -H " 2  3  (septet,  1208, 5  A  J  -  17,  2,  4  H z  n  IH,  1.5 Hz), 4.98  774cm- ; 1  ).  1  (CH ) CH-, 3  b i s - a l l y l i c protons, J = 6, 1.5 Hz), 3.71 H ,  This colorless  0  7  ( . d  exhibited  H nmr (400 MHz,  6H  >  (CH ) CH-, 3  J - 7 Hz), 3.21  2  (s,  -  A  oil  3H, -OMe), 4.97  2  (dt, 2H,  (ddt,  IH,  (ddt, IH, H , J - 10, 2, 1.5 Hz), 5.87 B  - 235 (ddt,  IH, H , J - 17, 10, 1 Hz).  Exact Mass calcd. for C H i 0 S n  c  CH ):  317.0563;  3  1 2  2  (M""1  2  found: 317.0556.  Preparation of methyl  (Z)-2-(2-propenvl)-3-trimethylstannyl-2.6-  heptadienoate (195)  Following  general  procedure 5, to a cold (-98 C),  s t i r r e d solution  D  of methyl (Z)-2,3-bis(trimethylstannyl)-2,6-heptadienoate  (133)  (2.049  g, 4.378 mmol) i n 70 mL of dry THF was added a solution of methyllithium (4.816 mmol) i n ether.  After the mixture had been s t i r r e d at -98°C  10 min, 3-iodopropene  (8.75 mmol) was added and the solution was s t i r r e d  at -98°C for 30 min and at -78°C for 1.5 h. distillation  (air-bath  temperature  011 afforded 1.129 mg (75%) of the exhibited  ir  (film):  Normal workup, followed  ester  (195).  This  3  S n  -H ~  (m,  2H,  Hz),  3.20 (dt, 2H, b i s - a l l y l i c protons, J - 6, 1.5  -  5  4  Hz  >> 3  2  2  4.95-5.08 (m, 4H, v i n y l protons),  2  2  Hz),  S n  3.74  -H " (s,  +  2 1  2  3  6  2  3H,  5.81 (ddt, IH, v i n y l proton, J  17, 10, 6 Hz), 5.84 (ddt, IH, v i n y l proton, J - 17, 10, 6 Hz).  Mass c a l c d . for C H 0 S n (M -CH ):  X  1.99-2.07  CH CHCH CH -), 2.53 (t, 2H, CH CHCH CH , J - 8 Hz, J  1 3  oil 1  2  -OMe),  colorless  3079, 1700, 1640, 1437, 1284, 1214, 770 cm" ; H  3  2  by  8 0 - 8 5 ° C / 0 . 0 5 Torr) of the residual  nmr (400 MHz, CDC1 ) 6: 0.15 (s, 9H, -SnMe , J 2  for  329.0564;  found: 329.0566,  Exact  - 236 -  General Procedure 6:  Preparation of c y c l i c  fl-trimethylstannyl  a.B-  unsaturated esters and N.N-dimethylamides  To a cold ( - 9 8 ° C ) , or  s t i r r e d solution of the  appropriate  (Z)-w-halo-2,3-bis(trimethylstannyl)-2-alkenoates  (1  alkyl  (E) -  equiv) or the  (E) -N,N.-dimethyl- 2,3-bis(trimethylstannyl) - w-bromo-2-alkenamide (1 equiv) in  dry  THF was  added  a solution of methyllithium (1.1-1.2 equiv)  ether and hexamethylphosphoramide (2-3  equiv).  solution  1  example). (20  was  stirred  -98°C  for  h  temperature.  were  added  concentrated.  The  yellow  mL/mmole)  and  ether  and the mixture was allowed to warm to room  The organic layer was washed three  ammonium  resulting  (with the exception of one  Saturated aqueous ammonium chloride (2  mL/mmole)  aqueous  at  The  in  chloride, remaining  times  with  saturated  dried over anhydrous magnesium sulfate and material  was  flash  chromatographed  on  s i l i c a gel ( e l u t i o n with petroleum ether-diethyl ether) and the o i l thus obtained was d i s t i l l e d (receiving bulb cooled to -78°C) to  afford  pure  product.  Preparation of methyl 2-trimethylstannvl-l-cvclopentenecarboxvlate  205  (a)  Following  (205)  139  general procedure 6, to a cold (-98 C), C  s t i r r e d solution  - 237 of the bis(trimethylstannyl)  ester (139)  (570 mg, 1.065 mmol) i n  12 mL  of dry THF was added 0.35 mL (2 equiv) of HMPA and a solution of methyllithium (1.268 mmol) i n ether. -98°C  for  50  min,  After the mixture had  gel (25  by g,  flash  obtained, colorless  with  (air-bath  afforded 231 oil  3.70  275.0094;  temperature mg  0.16  3  Hz),  petroleum  exhibited  (80 MHz, CDC1 ) 6: methylene  protons, (s,  at  temperature.  Normal  workup,  column chromatography of the residual o i l on s i l i c a  elution  distillation  stirred  saturated aqueous ammonium chloride and ether were  added and the mixture was warmed to room followed  been  2H,  3H, -OMe).  (74%)  of  i r (film): (s,  ether-diethyl 65°C/0.1 the  9H, -SnMe.3,  2  J = 7 Hz), 2.60 Exact  Mass  Torr)  cyclic  1700, J  1595, S n  -H ~  (t,  calcd.  ether; of  5  the  ester 1260, 5  Hz  14:1)  and  o i l thus  (205).  This  770 c m ; ^-H nmr - 1  )>  !-  8  7  (quintet,  4H, a l l y l i c protons, J = 7 for  C H 0 Sn 9  1 5  2  (M+-CH3):  found: 275.0086.  Br 1 38 (b)  Following  general procedure 6, to a cold ( - 9 8 ° C ) ,  of the bis(trimethylstannyl) of  ester (138)  s t i r r e d solution  (4.692 g, 8.06 mmol) i n 100  mL  dry THF was added 4.3 mL (3 equiv) of HMPA and a solution of methyl-  l i t h i u m (9.43 chromatography  mmol) and  c y c l i c ester (205). and s p e c t r a l l y  in  ether.  Normal  workup,  followed  d i s t i l l a t i o n as i n (a) afforded 1.73  by  column  g (73%) of the  This material was chromatographically (glc and t i c )  ( i r , ^H nmr) i d e n t i c a l with the material prepared i n  (a).  - 238 -  C0 Me  Me Sn  2  3  SnMe  3  Cl (c) Following general procedure 6, the bis(trimethylstannyl) (73 mg, 0.148 mmol) was converted into mixture  the  cyclic  ester  ester  (146)  (205).  The  was s t i r r e d at -98°C for 30 min and at -78°C for 1.5 h.  workup, followed by column chromatography and afforded  29  mg  (69%)  of  the  c y c l i c ester (205).  chromatographically (glc and t i c ) with the material prepared i n  distillation  and s p e c t r a l l y  (ir,  Normal  as  in  This material was nmr)  identical  (a).  Preparation of methyl 2-trimethvlstannvl-l-cvclohexenecarboxvlate  Me Sn 3  general  procedure 6, to a cold ( - 9 8 ° C ) ,  of the bis(trimethylstannyl) of  dry  ester (140)  3  (728 mg, 1.326  s t i r r e d solution mmol) i n  15 mL  THF was added a solution of methyllithium (1.591 mmol) i n ether  and 0.43 mL (2 equiv) of HMPA. -98°C  SnMe  (206)  Br  206 Following  (a)  for  50  min,  After the mixture had  by  stirred  at  saturated aqueous ammonium chloride and ether were  added and the mixture was warmed to room followed  been  temperature.  Normal  workup,  flash column chromatography of the resultant yellow o i l on  - 239  s i l i c a gel  (30 g , e l u t i o n w i t h petroleum e t h e r - d i e t h y l  distillation obtained,  (air-bath  oil  mg  exhibited  MHz, CDC1 ) 6:  0.14  3  -OMe).  temperature  a f f o r d e d 289  colorless  methylene  -  (s,  protons),  (72%) ir  70°C/0.05  of  the  (film):  Torr)  cyclic  1695,  1240,  9H, -SnMe.3, J _ s - H " 2  5  5  Hz  n  2.24-2.46  E x a c t Mass c a l c d .  (m,  ether; of  H  S n  and  the o i l  ester  (206).  770 c m " ; ^  thus This  nmr  1  > > 1 - 5 2 - 1 . 7 0 (m,  4H, a l l y l i c p r o t o n s ) ,  for C i o 1 7 ° 2  17:1)  (M+-CH3):  3.73  4H,  (s,  289.0251;  (270  3H,  found:  289.0251.  P r e p a r a t i o n o f methyl 2 - t r i m e t h y l s t a n n v l - l - c v c l o h e p t e n e c a r b o x y l a t e  Me Sn  C0 Me  3  Me Sn  2  SnMe  3  (207)  3  207 Following  general  procedure 6,  o f the b i s ( t r i m e t h y l s t a n n y l ) of  d r y THF was added 1.1  lithium -98°C  ester  (142)  mL (3 e q u i v )  (2.538 mmol) i n e t h e r . for 1 h,  to a c o l d ( - 9 8 " C ) , s t i r r e d s o l u t i o n (1.308 g , 2.14 mmol) i n  A f t e r the mixture had  been  stirred  at  s a t u r a t e d aqueous ammonium c h l o r i d e and e t h e r were added Normal workup,  followed  f l a s h column chromatography o f the r e s u l t a n t crude o i l on s i l i c a g e l  (45 g , e l u t i o n w i t h p e t r o l e u m e t h e r - d i e t h y l tion  mL  o f HMPA and a s o l u t i o n o f m e t h y l -  and the m i x t u r e was warmed t o room temperature. by  30  (air-bath  temperature  a f f o r d e d 394 mg (58%)  65°C/0.05  o f the c y c l i c e s t e r  ether;  Torr)  97:3)  and  distilla-  o f the o i l thus o b t a i n e d ,  (207).  This  colorless  oil  - 240 -  exhibited  i r ( f i l m ) : 1694,  CDC1 ) 6:  0.10  methylene  protons),  3  (s,  1583,  9H, -SnMe.3,  2j  1281, -Sn-H  1260, "  5  771 cm' ; H nmr (270 MHz, 1  4  Hz  > •  X  1-35-1.47  1.72-1.84 (m, 2H, methylene protons),  2H, a l l y l i c protons),  2.57-2.65 (m, 2H, a l l y l i c protons),  -OMe).  c a l c d . for C H 0 S n ( M - C H ) :  Exact  Mass  +  1 1  1 9  2  3  (m,  4H,  2.50-2.57 (m, 3.70  (s,  303.0407;  3H,  found:  303.0407.  Preparation of  N.N-dimethyl-2-trimethylstannyl-1-cyclopentenecarboxamide  (208)  208 Following  general  procedure 6, to a cold ( - 9 8 ° C ) ,  of the bis(trimethylstannyl)  amide (175)  s t i r r e d solution  (146 mg, 0.267 mmol) i n 5 mL of  dry THF was added 0.1 mL (2 equiv) of HMPA and a solution of methyllithium (0.32 mmol) i n ether. for  1  h,  After the mixture had been s t i r r e d  distillation  (air-bath  exhibited i r ( f i l m ) : 1636,  protons,  (s,  Normal workup, followed  1499,  9H, -SnMe.3, J_Sn-H ~ 2  amide  1392, 5  5  Hz  (208).  This  colorless  2.96  (s,  3H,  oil  772 cm" ; H nmr (400 MHz, CDCI3) 1  >>  X  -  9  3  X  (quintet,  2H,  J - 7.5 Hz), 2.51-2.58 (m, 2H, a l l y l i c protons),  2H, a l l y l i c protons),  by  temperature 1 1 0 ° C / 0 . 5 Torr) of the r e s i d u a l o i l  afforded 57 mg (70%) of the c y c l i c  0.14  -98°C  saturated aqueous ammonium chloride and ether were added and  the mixture was warmed to room temperature.  6:  at  -OMe).  Exact  Mass  methylene  2.60-2.68 (m, calcd.  for  - 241 C H N O S n (M+-CH3): 10  288.0410;  18  VII.  found: 288.0409.  Synthesis of stereochemically defined t r i s u b s t i t u t e d v i n y l  Preparation of  (Z)-2-(2-methvl-2-propenyl)-3-trimethylstannyl-3-cyclo-  propyl-2-propen-l-ol  To  a  cold  (214)  (-20°C),  stirred  solution of the ester (193)  0.593 mmol) i n 15 mL of dry d i e t h y l ether was added mmol).  The  mixture  was  stirred  decahydrate (-50 mg) was added temperature.  at  and  -20°C  the  mg,  0.30  Sodium sulfate warmed  to  room  E l u t i o n of the r e s u l t i n g s l u r r y through a short column of followed by concentration of  thus obtained, afforded 127 mg (68%) of  colorless  oil  exhibited  1  X  3  Hz),  0.29-0.35  (m,  2H),  1.40-1.50 (m, IH), 1.76 protons), 4.02 J - 1 Hz), 4.79 H i0 2  1 1 8  the  alcohol  0.73-0.81  (s,  0.21 (m,  (s,  9H, -SnMe.3, J_s -H 2  n  2H), 1.28  3H, v i n y l methyl), 3.18  (dd, 2H, -CH 0H, J - 6, 1 Hz), 4.69  This  (d, IH, v i n y l proton, J - 1 Hz). 298.0530;  (t,  (s,  1024, ~  5  2  IH, J - 6 Hz),  2H,  bis-allylic  (d, IH, v i n y l proton,  2  S n (M+-CH3):  (214).  i r (film): 3373 (br), 3076, 1649, 1606,  769 cm" ; H nmr (400 MHz, CDC1 ) 6:  1 2  was  (204 mg,  eluate and d i s t i l l a t i o n (air-bath temperature 9 0 ° C / 0 . 1 Torr) of the  oil  C  LAH (12  for 4 h.  mixture  F l o r i s i l (3 g, e l u t i o n with d i e t h y l ether), the  iodides  Exact Mass c a l c d .  found: 298.0526.  for  - 242 Preparation of  (Z)-2-(2-methvl-2-propenyl)-3-trimethylstannyl-4-tert-  butvldimethylsiloxv-2-buten-1-ol  To  (213)  a s t i r r e d solution of the ester (189)  (221 mg, 0.478 mmol) i n 10  mL of dry d i e t h y l ether was added LAH (16 mg, 0.42 mmol). was  stirred  at  room temperature for 18 h.  (-50 mg) was added. column  of  concentration of 110°C/0.05  the  g,  elution  eluate  and  1080,  845,  780 (s,  Bu Me Si-),  (t,  1.26  t  2  cm" ; 1  X  d i e t h y l ether),  distillation  a  short  followed by  (air-bath  bis-allylic  -SnMe.3,  9H,  temperature  t  2  3  J_s -H "  proton).  found: 405.1280.  n  2  iSn-H  ~  5  4  H z  ) > °-  0.04 8  9  (s, 6H, (> s  9H  >  IH, -OH, J — 6 Hz; addition of D 0 resulted i n the 2  protons),  Bu Me SiOCH -,  H nmr (400 MHz, CDC1 ) 6: 3  disappearance of t h i s s i g n a l ) ,  vinyl  through  This colorless o i l exhibited i r (film): 3350 (br), 3060,  B ^ M e ^ S i - ) , 0.21  2  with  slurry  Torr) of the o i l thus obtained, afforded 130 mg (65%) of the  alcohol (213). 1640,  (3  mixture  Sodium sulfate decahydrate  Elution of the r e s u l t i n g  Florisil  The  3.04 4  8  Hz  > •  1.73 (s, (d, 4  -  2H, 7  0  <> s  3H, v i n y l methyl), 2.92 -CH 0H, 2  1H  >  v  J - 6 Hz), 3.32  i y l proton), 4.78 n  Exact Mass c a l c d . for CigH330 SiSn (M+-CH3): 2  (s,  2H,  (s, 2H,  (s, IH, 405.1272;  - 243 Preparation of penten-l-ol  (Z)-4-methyl-2-(2-propenvl)-3-trimethylstannyl-2-  (212)  To a cold ( - 7 8 ° C ) , s t i r r e d solution of the ester (194) mmol)  in  70  at  0 C  for  C  1 h.  The mixture was s t i r r e d at -78°C for  warm  to  room  ether).  mg  (film):  (97%)  of  the  alcohol (212).  3336 (br), 1637,  9H, -SnMe ,  (t,  IH, -CH 0H, J - 7 Hz), 2.96  2  3  J  S n  -H "  1031,  (s,  5  2  H z  )•  2  772 c m ; - 1  1  -  0  0  <> d  X  3  6H  >  ( C H ) C H - , J - 7 Hz), 3  (septet, IH, ( C H ) C H - , J - 7 Hz), 3  (ddt, IH, H , J - 10, 2, 1.5 Hz), 5.03 B  H  0 S n  (M  4 -  -^):  IH, H , J - 17, 10, 6 Hz). c  289.0615; found: 289.0613.  0.24 1.17  2  3.02  2  5.00  (ddt,  afforded  H nmr (400 MHz, CDC1 ) 6:  Hz),  2, 1.5 Hz), 5.83  oil  This c o l o r l e s s o i l exhibited i r  2H, b i s - a l l y l i c protons, J - 6, 1.5 Hz), 4.04  ll 21  The  (20 g, e l u t i o n with  residual  (dt,  c  temperature.  Concentration of the combined eluate and d i s t i l l a t i o n  (air-bath temperature 7 0 - 7 5 ° C / 0 . 0 5 Torr) of the 747  h  white s l u r r y was treated with anhydrous magnesium sulfate and  then was f i l t e r e d through a short column of F l o r i s i l diethyl  1  Saturated aqueous ammonium chloride (-1 mL) was  added and the mixture was allowed to resulting  2.53  mL of d i e t h y l ether was added 6.32 mL (6.32 mmol) of a IM  s o l u t i o n of DIBAL i n hexane. and  (840 mg,  (d, 2H, -CH 0H, J - 7 2  (ddt, IH, H , J A  -  17,  Exact Mass c a l c d . for  - 244 Preparation of (Z)-2-(2-propenyl)-3-trimethylstannyl-2-penten-l-ol  To a cold ( - 7 8 ° C ) , s t i r r e d solution of the  ester  (179)  (211)  (1.469  g,  4.63 mmol) i n 100 mL of d i e t h y l ether was added 11.58 mL (11.58 mmol) of a 1M s o l u t i o n of DIBAL i n hexane. 1  h  and at 0°C for 1.5 h.  workup (see p. 243),  allowed  to  warm  to  room  temperature.  followed by d i s t i l l a t i o n (air-bath tempera-  ture 8 5 - 9 0 ° C / 0 . 0 5 Torr) of the residual o i l afforded 1.262 the  alcohol  3079, 1637, -SnMe , 3  2  J  (211). 1614,  S n  -H  =  5  2  Hz  -OH, J = 6 Hz), 2.30  769 cm- ; 1  > • °-  9  1  1  (> fc  3H  >  - 2 - 3 . J_ = 8 Hz) , 1.20 CH  3  2  3  Hz),  5.0  1.5  Hz),  IH, H , J = 10, 2, 1.5 Hz), 5.05 B  1 0  1 9  c  275.0458; found: 275.0456.  S n  -H =  6  9  Hz  >>  2  •  9  9  (d, 2H, -CH 0H, J - 6 2  (ddt,  (ddt, IH, H , J = 17, 10, 6 Hz).  C H O S n (M+-CH3):  (s, 9H, (t, IH,  CH  (q, 2H, - C H C H , J = 8 Hz, J  of  3348 (br),  3  2H, b i s - a l l y l i c protons, J = 6, 1.5 Hz), 4.05  5.81  (94%)  H nmr (400 MHz, CDC1 ) 5: 0.18  (dt,  (ddt,  g  This colorless o i l exhibited i r (film):  997,  for  Saturated aqueous ammonium chloride (~1 mL)  was added and the mixture was Normal  The mixture was s t i r r e d at -78°C  IH, H , J - 17, A  Exact Mass c a l c d .  2, for  - 245 -  Preparation of (Z) -l-methoxymethoxv-2- (2-propenvl') -3-trimethvlstannyl-2pentene  (215)  To a cold ( - 7 8 ° C ) ,  s t i r r e d solution of the  alcohol  (211)  0.307 mmol) i n 2 mL of dry dichloromethane was added 320 of N,N-diisopropylethylamine and 69 J J L (0.913 chloride.  The  mixture  temperature for 3 h. mL)  was  added  three times anhydrous  the  magnesium  at  0"C  for  of  methoxymethyl  10 min and at room  oil  product.  material on s i l i c a gel  sodium  bicarbonate,  and concentrated.  consisted  of  Flash  (15  g,  ether  (15  The organic solution was then washed  aqueous  sulfate  protodestannylated  ether; 9:1),  residue.  saturated  that the resultant  stirred  mg,  (5.481 mmol)  It was then concentrated and petroleum  to  with  was  mmol)  (89  92%  elution  Glc analysis  of  (215)  column  dried  and  indicated  7% of  chromatography  with  petroluem  over  of  the this  ether-diethyl  followed by d i s t i l l a t i o n (air-bath temperature  80-85°C/0.05  Torr) of the o i l thus obtained, afforded 81 mg (79%) of the ether (215). This  colorless  769 c m ' ; 1  Hz),  0.92  X  oil  exhibited i r (film): 3079, 1638,  H nmr (400 MHz, CDC1 ) 6: 0.18 3  (t,  3H,  (s,  1614,  9H, -SnMe ,  2  3  J  1152, S n  -H  1037, -  5  4  - C H C H , J - 8 Hz), 2.31(q, 2H, - C H C H , J • 8 Hz, 2  3  2  3  J-Sn-H - 66 Hz), 2.98  (dt, 2H, b i s - a l l y l i c protons, J - 6, 1.5 Hz), 3.38  (s,  (s,  3  3H,  -OMe), 3.96  -CH OCH OMe), 5.00 2  J  -  2  17,  2H, -CH OCH OMe, 2  2  4  J  S  n  .  H  - 10 Hz), 4.62  (ddt, IH, H , J - 10, 2, 1.5 Hz), 5.04  2, 1.5 Hz), 5.80  B  (ddt, IH, H ,  (ddt, IH, H , J -= 17, 10, 6 Hz). c  (s, 2H, A  Exact Mass  - 246 c a l c d . for C H 3 0 S n (M+-CH ): 12  2  2  319.0720; found: 319.0721.  3  Preparation of (Z)-3-iodo-2-(2-propenvl)-2-penten-l-ol  (220)  To a s t i r r e d s o l u t i o n of the v i n y l stannane (211) mmol)  in  (1.063  g,  3.665  40 mL of dry dichloromethane was added 931 mg (3.665 mmol) of  s o l i d iodine.  The mixture was s t i r r e d at room temperature u n t i l a  yellow  persisted.  color  Concentration  of  the s o l u t i o n , followed by  f l a s h column chromatography of the residual o i l on elution  with  petroleum  ether-diethyl  ( a i r - b a t h temperature 7 0 - 7 5 ° C / 0 . 0 5 afforded  575  mg  (63%)  ether;  Torr)  of  X  H  nmr  silica  7:3) the  (400 MHz, CDCI3) 6: 1.07  (t,  1455,  and  oil  of the iodo alcohol (220).  exhibited i r ( f i l m ) : 3319 (br), 3079, 1638,  pale  gel  (30  distillation  thus  obtained,  This colorless  1087,  1010,  828  3  bis-allylic  (d, 2H, -CH 0H, J - 6 Hz),  5.06  protons,  -  6, 1.5 Hz), 4.24  (ddt, IH, H , J - 10, 2, 1.5 Hz), 5.08 B  Hz),  5.76  (ddt,  C H I O (M+): 8  J  1 3  IH,  H , c  J  -  2H,  2  (ddt, IH, H , J - 17, 2,  17, 10, 6 Hz).  252.0013; found: 252.0007.  (dt,  (t,  7.5  3  3.09  1  IH, -OH, J - 6 Hz), 2.61(q, 2H, - C H C H , J 2  Hz),  oil  cm" ;  3H, - C H C H , J - 7.5 Hz), 1.64 2  g,  A  1.5  Exact Mass c a l c d . for  - 247 Preparation of 2-pentene  (Z)-3-iodo-1-(2-methoxvethoxv)methoxy-2-(2-propenyl)-  (221)  o  To a s t i r r e d s o l u t i o n of the iodo alcohol (220) in  15  mL of  dry  dichloromethane  was  chloride.  The  mmol)  organic  Petroleum ether (50 mL)  solution  and  2-methoxyethoxy  concentrated.  was  Distillation  anhydrous  (air-bath  1 1 5 - 1 2 0 ° C / 0 . 0 5 Torr) of the residual o i l afforded 666 mg ether (221).  This colorless o i l exhibited i r (film):  1199-1040 (br), 916 cm" ; ^-H nmr 1  -CH CH , 2  J  3  -  6  Hz),  2.61  (400  MHz, CDC1 )  3.72-3.77  -CH OCH 0-), 2  -  17,  5.03  2  2,  (m,  1.5  2H),  2  2H,  3  (s,  3H, -OMe),  -CH OCH 0-), 2  3  ?  2  of  2  (t  the 1456, 3H,  (dt, 2H,  3.55-3.61  (m,  4.75  2H,  (s,  (ddt, IH, H , J  c  +  1 4  1.09  (ddt, IH, H , J - 17, 10, 6 Hz).  c a l c d . for C H I 0 ( M - C H 0 ) : 9  (s,  B  5.75  (88%)  3079, 1639,  (ddt, IH, H , J - 10, 2, 1.5 Hz), 5.05 Hz),  the  magnesium  (q, 2H, - C H C H , J - 6 Hz), 3.05  4.22  to  temperature  6:  3  b i s - a l l y l i c protons, J - 6, 1.5 Hz), 3.41 2H),  added  was washed three times with saturated  aqueous sodium bicarbonate and then was dried over sulfate  of  The solution was s t i r r e d for 15 h at room temperature  and then was concentrated. residue.  mmol)  added 1.17 mL (6.705 mmol) of  N,N-diisopropylethylamine and 0.76 mL (6.705 methyl  (563 mg, 2.23  265.0091; found: 265.0082.  A  Exact Mass  - 248 Preparation of (Z)-3-iodo-4-methvl-2-(2-propenyl)-2-penten-l-ol  To a s t i r r e d solution of the v i n y l stannane mmol)  in  30  (212)  (736  mg,  2.421  mL of dry dichloromethane was added s o l i d iodine (615 mg,  2.421 mmol).  The mixture was s t i r r e d at room temperature u n t i l  yellow color p e r s i s t e d .  petroleum  a  pale  Concentration of the solvent, followed by flash  column chromatography of the residual o i l on s i l i c a gel (35 with  (222)  ether-diethyl  ether;  7:3)  g,  and d i s t i l l a t i o n  elution (air-bath  temperature 7 0 - 7 5 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 459 mg (71%)  of  (film): 6:  iodo  alcohol  3078 (br), 1638,  0.99  2.37  the  1617,  (222). 1038,  3  1  2  3  J  -  2  -  7  colorless  o i l exhibited i r  990, cm* ; H nmr (400 MHz,  (d, 6H, ( C H ) C H - , J - 7 Hz), 1.68  (septet, IH, ( C H ) C H - , J  protons,  This  Hz),  (t, 3.16  X  CDC1 ) 3  IH, -CH 0H, J = 7.5 Hz), 2  (dt,  2H,  bis-allylic  6, 1.5 Hz), 4.27  (d, 2H, -CH 0H, J - 7.5 Hz), 5.06  (ddt,  IH, H , J - 10, 2, 1.5 Hz), 5.07  (ddt, IH, H , J - 17, 2, 1.5 Hz),  5.80  B  (ddt,  IH,  H , c  2  J - 17, 10, 6 Hz).  266.0169; found: 266.0167.  A  Exact Mass calcd. for C H O I (M+) : 9  15  - 249 Preparation of  (Z)-3-iodo-l-(2-roethoxyethoxv)methoxv-4-methyl-2-(2-  propenyl)-2-pentene  (223)  o—  To a s t i r r e d solution of the alcohol (222) of  dry  mmol)  (266 mg, 1 mmol) i n 15 mL  dichloromethane was added N,N-diisopropylethylamine (0.35 mL, 2  and  solution  2-methoxyethoxymethyl  chloride  (0.24  mL,  2  mmol).  was s t i r r e d at room temperature for 13 h, and then was concen-  trated.  Petroleum ether (20 mL) was added to the residue.  solution  was  The  organic  washed three times with saturated aqueous sodium bicarbo-  nate, d r i e d over anhydrous magnesium sulfate and concentrated. lation  (air-bath  temperature  100 C/0.05  Torr)  6  afforded 331 mg (93%) of the ether (223). ir  (film):  3079, 1638,  CDC1 ) 5: 0.97  (d,  3  1620,  6H,  ( C H ) C H - , J - 7 Hz), 3.12 3  3.31  2  (s,  of  the  - 1  (CH ) CH-, 3  (dt,  2  J  residual o i l  This colorless o i l  1197-992 (br), 850 c m ; -  7  Hz),  X  Distil-  exhibited  H nmr (400 MHz,  2.38  (septet,  2  Hz),  5.04  10,  6  (s,  2H, -CH OCH 0-), 5.03 2  2  B  A  Exact  found: 265.0088.  Mass  calcd.  (ddt, IH, H , J c  for C H 0 I ( M - C H 0 ) : +  9  (s,  (ddt, IH, H , J - 10, 2,  (ddt, IH, H , J - 17, 2, 1.5 Hz), 5.75  Hz).  IH,  2H, b i s - a l l y l i c protons, J - 6, 1.5 Hz),  3H, -OMe), 3.56-3.64 (m, 2H), 3.72-3.79 (m, 2H), 4.26  -CH 0CH 0-), 4.75 2  The  1 4  3  4  9  2  -  2H, 1.5 17,  265.0091;  - 250 Preparation of (Z)-3-iodo-2-(2-propenvl)-2-pentenal  (226)  H  To a s t i r r e d solution of mmol)  in  4  mL of  pyridinium  chlorochromate  for  dichloromethane.  was  passed  (air-bath  afforded 196 mg  through  1.18  Hz),  (t,  3.12  temperature (82%)  of  2  120-125°C/20 the  aldehyde 1681,  IH, H , J - . 1 7 , i;L  The  elution  of  the  This  residual o i l colorless  1  X  3  (q, 2H,  B  10, 6 Hz), 9.64  oil  1274 cm" ; H nmr (80 MHz, CDC1 )  (ddt, IH, H , J -  for C H 0 I (M+): 249.9856; found: 8  (15 g,  -CH CH , 2  3  2H, b i s - a l l y l i c protons, J - 6, 1.5 Hz), 4.80  A  c  Torr) (226).  3  H , J - 17, 2, 1.5 Hz), 5.00 (ddt,  ether.  Concentration of the eluate, followed by d i s t i l l a -  3H, - C H C H , J - 7.5 Hz), 2.88 (dt,  diethyl  a short column of F l o r i s i l  exhibited i r ( f i l m ) : 2859, 1729, 6:  (0.47  The brown mixture was s t i r r e d at room temperature  with d i e t h y l ether). tion  1.9  (241 mg, 0.95 mmol) i n 2 mL of  1 h 45 min and was then poured into 50 mL of  mixture  mg,  dry dichloromethane was added sodium acetate  mmol) and a solution of the alcohol (220) dry  (412  (s,  10,  IH, -CHO).  249.9858.  2,  1.5  J  =  7.5  (ddt, IH, Hz),  5.70  Exact Mass c a l c d .  - 251 Preparation of (E)-5-iodo-4-vinyl-l.4-heptadiene  (227)  To a s t i r r e d solution of methylenetriphenylphosphorane (1.9 mmol) i n 8 mL of dry THF was added a solution of the aldehyde (226) mmol) i n 2 mL of dry THF. temperature.  It  was  (189 mg, 0.75  The red solution was s t i r r e d for 2 h at  then  added  to 30 mL of petroleum ether and the  resultant s l u r r y was passed through a short column e l u t i o n with petroleum ether).  of  Florisil  afforded 146 mg (78%) of the iodo triene (227).  exhibited i r (film): 3080, 1677, 6: 1.12 3.15 =  (t,  (dt,  10,  2,  E  6  Hz),  C H I  (M+):  9  1 3  920 c m ; - 1  3  1.5 Hz), 5.04  6.69  X  248.0064;  residual  H nmr (400 MHz, CDC1 ) 3  2  3  (ddt, IH, H , B  (ddt, IH, H , J - 17, 2, 1.5 Hz), 5.16 A  IH, H , J = 17, 11 Hz). D  found: 248.0057.  oil  (q, 2H, - C H C H , J •= 7.5 Hz),  (d, IH, Hp, J = 17 Hz), 5.76 (dd,  g,  This colorless  2H, b i s - a l l y l i c protons, J = 6, 1.5 Hz), 5.02  H , J - 11 Hz), 5.29 10,  1638,  3H, - C H C H , J = 7.5 Hz), 2.72 2  (5  Concentration of the eluate, followed by  d i s t i l l a t i o n (air-bath temperature 1 1 0 - 1 1 5 ° C / 0 . 0 5 Torr) of the oil,  room  (d, IH,  (ddt, IH, H , J = c  J  17,  Exact Mass c a l c d . for  - 252 Preparation of (Z)-3-iodo-2-(2-propenyl)-2.6-heptadien-l-ol  To a cold ( - 7 8 ° C ) , 3.28  mL)  s t i r r e d solution of the  ester  (228)  (195)  (1.129  i n 100 mL of dry diethyl ether was added 6.56 mL (6.56  of a 1 M s o l u t i o n of DIBAL i n  hexane.  at  0°C  -78°C  for  1  h  and  at  The  resulting  white  mmol)  The reaction mixture was s t i r r e d  for 2 h.  Saturated aqueous ammonium  chloride (-2 mL) was added and the mixture was allowed to warm temperature.  g,  slurry  was  to  room  treated with anhydrous  magnesium s u l f a t e ,  and the mixture was passed through a short column  Florisil  elution with diethyl ether).  (10  g,  concentrated, affording a colorless o i l . oil  The combined eluate was  To a s t i r r e d solution of  this  i n 70 mL of dry dichloromethane was added s o l i d iodine u n t i l a pale  purple color p e r s i s t e d . phy  of  the  residual  ether-diethyl  ether;  84-88°C/0.05  Torr)  Concentration, followed by column oil 3:1)  of  the iodo alcohol (228). (br), (t,  of  3078,  1640,  1H,-CH 0H,  2H,  2  2  0.5 Hz), 4.25 (ddt,  2  on s i l i c a gel (20 g, e l u t i o n with petroleum and  2  distillation  (air-bath  temperature  the o i l thus obtained, afforded 610 mg (67%) of This colorless o i l exhibited  1445,  995, 915 c m ;  ir  (film):  1.64  (q, 2H, CH CHCH CH -, J - 6 Hz) 2.65  (t,  X  3  2  J - 6 Hz), 3.10 (dt,  2  2  2H, b i s - a l l y l i c protons, J - 6,  (d, 2H, -CH 0H, J - 6 Hz), 4.97-5.15 (diffuse m, 4H), 2  IH, v i n y l proton, J - 17, 10, 6 Hz), 5.80  J -= 17, 10, 6 Hz).  Exact  Mass  3332  H nmr (400 MHz, CDC1 ) 6:  - 1  J - 6 Hz), 2.30  CH CHCH CH -,  chromatogra-  calcd.  for  (ddt, IH, v i n y l proton,  C H OI 1 0  5.78  1 5  (M+):  278.0165;  - 253 found: 278.0167.  Preparation of (Z)-3-iodo-2-(2-propenyl)-2.6-heptadienal  (229)  H  To  a  stirred  solution of pyridinium chlorochromate (620  mmol) i n 12 mL of dry dichloromethane was added mmol) and a solution of the alcohol (228) of dry dichloromethane. ture  for  1.5  (400  temperature  afforded  mg  360  (91%)  70-75°C/0.05 of  2.40  Hz), Hz), Hz), Hz),  2  5.00 5.04 5.68  2  9.65  2  (ddt, IH, J - 9.5,  (s,  1589,  2  g,  1.5,  1 Hz), 5.11  the  residual  oil  This pale yellow o i l 917 c m ; - 1  X  H nmr (300 (t, 2H,  J  -  (ddt, IH, J - 9.5, (ddt, IH, J - 15,  6 Hz), 5.80  The  elution  2  1 Hz), 5.02  IH, J - 15, 9.5,  IH, -CHO).  found: 276.0009.  of  (dt, 2H, b i s - a l l y l i c protons,  (ddt, IH, J - 15, 1.5,  (ddt,  Torr)  1640,  (15  (qd, 2H, CH CHCH CH -, J •= 6, 1 Hz), 2.99  CH CHCH CH -, J - 6 Hz), 3.16 2  mmol) i n 8 mL  followed by d i s t i l l a -  the aldehyde (229).  exhibited i r (film): 3079, 2737, 1680, 6:  Florisil  Concentration of the eluate,  t i o n (air-bath  3  mg, 1.438  (0.719  h and then was poured into 100 mL of d i e t h y l ether.  with d i e t h y l ether).  CDC1 )  acetate  The brown solution was s t i r r e d at room tempera-  mixture was passed through a short column of  MHz,  sodium  mg, 2.87  6,  1  1.5,  1  1.5,  1  (ddt, IH, J - 15, 9.5, 6  Exact Mass c a l c d . for C H O I 1 0  1 3  (M+) :  276.0012;  - 254 Preparation of (Z)-5-iodo-4-vinvl-l.4.8-nonatriene  (230)  To a s t i r r e d solution of methylenetriphenylphosphorane in  (3.17  20 mL of dry THF was added a solution of the aldehyde (229)  mmol)  (339 mg,  1.228 mmol) i n 2 mL of dry THF, and the red solution was s t i r r e d at room temperature for 1 h.  The solution was added to 50 mL of petroleum ether  and the resultant s l u r r y was passed through a short column (5  g,  elution  with  petroleum  ether).  of  Florisil  Concentration of the eluate,  followed by d i s t i l l a t i o n {.air-bath temperature 6 5 - 7 0 ° C / 0 . 0 5 Torr) of the residual  oil,  afforded 300  mg (89%) of the iodo tetraene (230).  c o l o r l e s s o i l exhibited i r (film): 3079, 1640, nmr (t,  (400 MHz, CDC1 ) 3  6: 2.33  2  6, 1 Hz), 5.00  (ddt, IH, J - 10, 1.5,  (ddt, IH, J - 17, 1.5,  Hz),  (dd,  Hz), 6.70  2  2  1 Hz), 5.03 5.18 5.75 (dd,  2  1 Hz), 5.02  1 Hz), 5.08  E  (ddt, IH, J = 17, 10, 6 Hz), 5.81 IH, H , J - 17, 11 Hz).  274.0220; found: 274.0222.  cm' ; 1  X  H  2  (dt, 2H, b i s - a l l y l i c protons, J  IH, H , J - 11, 0.5 Hz), 5.30  D  987, 911  (qd, 2H, CH CHCH CH -, J = 6, 1 Hz), 2.77  2H, CH CHCH CH -, J = 6 Hz), 3.14 2  1613,  This  (ddt, IH, J - 10,  =  1.5,  (ddt, IH, J = 17, 1.5, (dd, IH, Hp, J = 17,  1 0.5  (ddt, IH, J - 17, 10, 6 Hz),  Exact Mass c a l c d . for C ^ H ^ I (M ) : +  - 255 Preparation of (Z)-l-chloro-4-methvl-2-(2-propenvl)-3-trimethylstannyl2-pentene  To  (233)  a  stirred  solution of the alcohol (212)  (380 mg, 1.25 mmol) i n  6 mL of dry carbon tetrachloride was added triphenylphosphine (656 2.51  mmol)  and  triethylamine  (191 fil,  1.375 mmol).  The solution was  refluxed for 12 h. Petroleum ether (20 mL) was added and s l u r r y was passed through a short column of F l o r i s i l petroleum ether). (air-bath  temperature  3080,  9H, -SnMe , 3  (septet,  2  1638,  J_s -H "  85-90°C/0.05  914, 5  2  H z  n  IH,  H ,  for  C H  Hg),  A  1 1  3 5 2 0  ClSn  Preparation of (234)  resulting  (10 g, e l u t i o n with  Torr) of the residual o i l afforded  3  5.80  1  colorless  oil  (s,  X  9  •=  5  ->  ( d  7  6H  >  (CH ) CH-, J 3  Hz),  2  3.02  8  H z  n  ) •  c  4 -  307.0276;  7  6: 0.27 Hz),  ir (s,  2.95  (broad d, 2H, b i s - a l l y l i c  2H, -CH C1, J_s -H ~ 2  -  (ddt, IH, H , J <= 17, 10, 6 Hz).  (M -^):  exhibited 3  J  2  This  774 cm" ; H nmr (80 MHz, CDC1 )  ) >°-  (CH ) CH-,  protons, J = 6 Hz), 4.03 2H,  the  Concentration of the eluate, followed by d i s t i l l a t i o n  368 mg (91%) of the chloride (233). (film):  mg,  4.85-5.17  (m,  Exact Mass calcd.  found: 307.0275.  (Z)-l-chloro-3-iodo-4-methyl-2-(2-propenyl)-2-pentene  - 256 To a s t i r r e d solution of mmol)  in  15  1.096 mmol). purple  the  vinylstannane  (353 mg,  1.096  mL of dry dichloromethane was added s o l i d iodine (278 mg, The solution was s t i r r e d at room temperature u n t i l a  color  persisted.  pale  It was then passed through a short column of  basic alumina (10 g, e l u t i o n with petroleum the  (233)  ether).  Concentration  of  eluate, followed by d i s t i l l a t i o n (air-bath temperature 5 5 - 6 0 ° C / 0 . 0 5  Torr) of the residual o i l afforded 306 mg (98%) This  colorless  o i l exhibited i r ( f i l m ) : 3081,  nmr (80 MHz, CDC1 ) 3  (septet,  0.95  IH, (CH )2CH-, 3  - 6, 1.5 Hz), 4.30 Hz),  5:  5.10  10, 6 Hz).  (s,  (d,  6H,  2  1638,  3  9  •=  7  (234).  919 cm" ; ^-H 1  Hz),  2.35  (dt, 2H, b i s - a l l y l i c protons, J  5.05  C H  iodide  1613,  J  2  (ddt, IH, H , J — 17,  2,  A  (ddt, IH, Hg, J - 10, 2, 1.5 Hz), 5.77 Exact Mass calcd. for  the  (CH ) CH-,  J = 7 Hz), 3.15  2H, -CH C1),  of  3 5 1 4  C1I  1.5  (ddt, IH, H , J - 17,  (M+) :  c  283.9831;  found:  283.9827.  Preparation of ethvl (Z)-2-iodo-3-trimethvlstannvl-2-butenoate  (235)  C0 Et 2  To  a  cold  (-78°C),  stirred  solution of the ester (124)  (338 mg,  0.765 mmol) i n 5 mL of dry dichloromethane was added 194 mg (0.765 mmol) of iodine as a solution i n 10 mL of dry dichloromethane. purple mixture had been s t i r r e d at -78°C for 30 warmed  to  room  temperature.  min  the  After the pale solution  was  Concentration, followed by d i s t i l l a t i o n  - 257 (air-bath temperature ~40°C/0.05 Torr) of Me3SnI and (air-bath  temperature  1718,  distillation  80°C/0.05 Torr) of the residual o i l afforded 280  mg (91%) of the stannyl iodide (235). (film):  then  1578,  1220,  0.32 (s, 9H, SnMe , J_s -H " 2  3  This colorless o i l  exhibited  ir  1033, 775 cm" ; H nmr (300 MHz, CDC1 ) 6: 1  X  3  5  6  H z  n  ) > 1  2.10 (s, 3H, vinyl methyl, J_s -H " 3  4  5  n  3  Hz  2  3H  > • 4  >  2  5  -OCH CH , J = 2  7 Hz),  3  <<1> >  -OCH CH , J = 7  2H  2  3  Hz). In a nOe difference experiment irradiation of the signal at 6  4.25  (-OCH CH3) caused signal enhancement at S 2.10 (vinyl methyl) and 6 1.32 2  (-OCH CH ); 2  1 3  3  C nmr (75.6  14.1 (q), 26.0 (q, (s).  2  J  S n  .  MHz, CDCI3) 6:  -6.9  (q,  X  ±sn-C  =  3  4  - 6 Hz), 61.7 (t), 93.6 (s), 163.7 (s), 3  H  Exact Mass calcd.  9  for  C H 0 ISn g  14  (M+-CH3) :  2  388.9064;  Hz  )>  164.4 found:  388.9064.  Preparation of methyl (Z)-2-iodo-3-trimethylstannyl-2-pentenoate  (236)  C0 Me 2  To  a  cold  (-78°C),  stirred  solution of the ester (125) (620 mg,  0.403 mmol) in 20 mL of dry dichloromethane mmol)  of  iodine.  After  the  was  added  358  mg (1.403  pale purple mixture had been stirred at  -78°C for 3.5 h the solution was warmed to room temperature.  Concentra-  tion, followed by d i s t i l l a t i o n (air-bath temperature -40°C/0.05 Torr) of Me SnI and then d i s t i l l a t i o n (air-bath temperature 80-85°C/0.05 Torr) of 3  the  residual  oil  afforded  550  mg (97%) of the stannyl iodide (236).  - 258 This c o l o r l e s s o i l exhibited i r (film): 1719, 1225, nmr 3H,  (300  MHz, CDC1 ) 6: 0.32  (s,  3  - C H C H , J - 7.5 Hz), 2.48 2  Hz),  388.9063;  (s,  3H,  -OMe).  9H, -SnMe , J_s -H " 2  3  5  4  H z  n  cm" ;  ti  1  ) • °-  9  L  ->  6  (  t  (q, 2H, -CH CH , J - 7.5 Hz, J_s -H " 3  3  3.76  1031, 778  2  3  5  5  n  Exact Mass c a l c d . for CgH^O^Sn (M+-CH;}):  found: 388.9063.  Preparation of methyl pentenoate  (E)-3-iododimethvlstannvl-2-trimethylstannyl-2-  (241)  C0 Me 2  To a s t i r r e d solution of the ester (147) mL  of  (420 mg, 0.95 mmol)  dry dichloromethane was added 242 mg (0.95 mmol) of iodine.  yellow mixture was s t i r r e d at room temperature for tion,  followed  by  distillation  (air-bath  Torr) of the residual o i l afforded 446 This nmr  colorless  2H,  -SnMe I, Isn-H 2  6  6  - C H C H , J - 7 Hz, J  Hz  3  2  3  MHz, CDC1 )  6:  3  15.3 (q,  Hz),  54.0  C H 0 ISn 1 0  =  2  (75.6 Hz),  (s,  3  2 0  2  3  J  S n  _  -  1  -H -  -6.1  9H, -SnMe ,  (s),  2  3  0  9  3  0  3H  >>  Hz  3  >  (s),  J  - 1  S n  -H "  3  5  5  Hz  >•  °-  9  8  2  J  <>  4  s  3  4  S  193.0  n  9 Hz  .  c  3H  <  > > 4  - 64  (s).  -PMfe); l j  6  Hz,  1 3  s  (q,  C nmr  Sn-C ~ 3  J  S  n  .  c  1  <>  5  3  ( M - C H ) : 538.8554; found: 538.8550. +  (241).  1540, 1283, 776 c m ; H  2  -  The  Concentra-  - C H C H , J - 7 Hz), 2.85  (q, ^ s n - C ~  176.5  min.  mg (85%) of the stannane  - 7.4 Hz), 33.1 (t,  c  (q), 139.6 2  S n  > •  30  15  temperature 1 2 0 - 1 2 5 ° C / 0 . 0 5  o i l exhibited i r (film): 1636,  (300 MHz, CDC1 ) 6: 0.29  6H,  in  4  -  6  4  37  Exact Mass c a l c d . for  - 259 Preparation of (Z)-2-iodo-3-trimethylstannvl-2-penten-l-ol  Me Sn 3  |  W  ' To a cold ( - 7 8 ° C ) ,  (248)  >—OH  s t i r r e d solution of the ester (236)  (534 mg,  1.32  mmol) i n 20 mL of dry d i e t h y l ether was added 2.9 mL of a 1M solution of DIBAL i n hexane. for  1 h.  The mixture was s t i r r e d at -78°C for 1 h  and  at  0°C  Saturated aqueous ammonium chloride (-1 mL) was added and the  mixture was warmed to room temperature.  Normal  workup  (see  pg.  243)  followed by subjection of the residual o i l to vacuum (0.1 Torr, -45 min) afforded 415 exhibited  mg  ir  CDC1 ) 6: 0.90 3  7 Hz), 1.54 Hz),  4.26  (t,  (dt,  VII.  the  alcohol  3349 (br), 1577,  (S, 9H, -SnMe , 3  2  J  S n  -H =  (248).  1020, 5  5  Hz  IH, -CH 0H, J = 6 Hz), 2.23 2  2H, -CH 0H, J 2  +  14  of  (film):  C H OISn(M -CH ): 7  (84%)  3  360.9113;  6,  1.5  This  colorless  oil  773 c m ; ^-H nmr (300 MHz, - 1  >-  1  (qt,  Hz).  -  1 6  ( . t  3H, - C H C H , J 2  3  2H, - C H C H , J = 7, 2  Exact  3  Mass  calcd.  1.5 for  found: 360.9121.  Synthesis of stereochemically  defined tetrasubstituted  alkenes  General procedure 7 : Preparation of v i n v l - l i t h i u m reagents and t h e i r reaction with electrophiles  To  a cold ( - 7 8 ° C ) ,  s t i r r e d solution of the appropriate v i n y l iodide  (1 equiv) i n dry THF was added a  solution  of  n-butyllithium  (1.2-2.2  - 260 equiv) i n hexane. min.  The r e s u l t i n g solution was s t i r r e d at -78°C for 10-15  A large excess of the appropriate  freshly  distilled  or  electrophile,  had  been  had been passed through basic alumina was added,  and the mixture was s t i r r e d at -78°C for 10 min-2 h. solution  which  In some cases  was then s t i r r e d at room temperature for up to 7 h.  aqueous ammonium chloride (-2 mL/mmol) and d i e t h y l ether  (-30  Saturated mL/mmol)  were added and the mixture was allowed to warm to room temperature. organic s o l u t i o n was then washed ammonium trated.  chloride,  dried  three  times  with  saturated  on  silica  The  aqueous  over anhydrous magnesium sulfate and concen-  The r e s u l t i n g o i l was either d i s t i l l e d d i r e c t l y or was  tographed  the  gel  chroma-  (elution with petroleum ether-diethyl  ether)  p r i o r to d i s t i l l a t i o n , thus affording pure product.  Preparation of heptadiene  (E)-4-(2-methoxyethoxy)methoxymethyl-5-methvl-l.4-  (257)  Following general procedure 7, to a cold ( - 7 8 ° C ) , of  the iodide (221)  been  stirred  by  After  the  mixture  at -78°C for 15 min, iodomethane (-3 mmol) was added  and the s o l u t i o n was s t i r r e d followed  solution  (40 mg, 0.1176 mmol) i n 2 mL of dry THF was added a  s o l u t i o n of n-butylithium (0.2588 mmol) i n hexane. had  stirred  distillation  at  -78°C  for  10  min.  Normal  workup,  (air-bath temperature 9 0 ° C / 0 . 0 5 Torr) of the  - 261 r e s i d u a l o i l afforded 25 oil  exhibited  i r (film):  MHz, CDC1 ) 6: 1.00  (t,  3  methyl),  mg (93%) of the diene (257).  2.10  (q,  3077, 1637,  2H,  1  3  -CH CH , 2  3  J  -  b i s - a l l y l i c protons, J - 6.5 Hz), 3.40 3.69  - 3.75  4.97  (ddt,  Hz),  5.78  C  (m, 2H), 4.07  (s,  2  H , c  1.78  Hz),  X  (s,  2.89  3H,  vinyl  (broad d, 2H,  3H, -OMe), 3.55-3.60 (m, 2H),  2H, -CH OCH 0-), 4.71 2  B  IH,  7.5  (s,  IH, H , J - 10, 2, 1 Hz), 5.01 (ddt,  colorless  1201 - 950 (br) cm" ; H nmr (400  3H, - C H C H , J - 7.5 Hz), 2  This  (ddt,  (s,  2H, -CH OCH 0-), 2  IH, H , J A  J - 17, 10, 6.5 Hz).  -  2  17,  2,  Exact Mass c a l c d .  1 for  1 3 2 4 ° 3 ( *"> 228.1725; found: 228.1726. H  K  :  Preparation of (Z) -5-ethvl-41.4.7-nonatriene  (2-methoxyethoxv)methoxymethyl-8-methvl-  (256)  Following general procedure 7, to a cold ( - 7 8 ° C ) , of  the iodide (221)  been  After  the  mixture  s t i r r e d at -78°C for 15 min, 1-bromo-3-methyl-2-butene  mmol) was added and the solution Normal  solution  (52 mg, 0.1529 mmol) i n 5 mL of dry THF was added a  s o l u t i o n of n-butyllithium (0.458 mmol) i n hexane. had  stirred  was  stirred  at  -78°C  for  30  (-3.0 min.  workup, followed by column chromatography of the residual o i l on  s i l i c a gel (10 g, e l u t i o n with petroleum ether-diethyl ether; distillation  3:1)  and  (air-bath temperature 1 1 0 - 1 1 5 ° C / 0 . 0 5 Torr) of the o i l thus  - 262 obtained,  afforded 29 mg (67%) of the triene  exhibited i r (film):  3077, 1637,  (400 MHz, CDC1 ) 6: 1.00  (t,  3  (CH ) -C-CH-), 3  1-69  2  Hz),  2.83  2H,  bis-allylic  2H),  3.68-3.74  (s,  3H,  (256).  3H, - C H C H , J - 7.5 2  Hz),  3  (CH3) -C=CH-), 2  (m,  2H),  J  2.06  - 6 Hz), 3.40  4.07  (s,  2H,  2  10, 6 Hz).  Exact Mass calcd. for C  1 3  H  X  1  1.67  2 0  (s,  3H,  (q, 2H, - C H C H , J 2  (s,  7.5  3  (broad d, 2H, b i s - a l l y l i c protons, J - 7 Hz), 2.89 protons,  oil  1173 - 960 (br), 850 cm" ; U nmr  1407,  (broad  d,  3H, OMe), 3.53-3.59 (m,  -CH OCH -),  - C H O C H - ) , 4.95-5.05 (m, 3H, v i n y l protons), 2  This colorless  2  5.78  4.71  2  (s,  2H,  (ddt, IH, H , J c  (M+'C^Ho^):  176.1565;  17,  found:  176.1562.  Preparation of (Z)-5-ethyl-4-(2-methoxvethoxv)methoxvmethvl-l.4nonadiene  (255)  Following  general  of the iodide (221) solution  of  procedure 7, to a cold ( - 7 8 ° C ) ,  s t i r r e d solution  (58 mg, 0.1705 mmol) i n 5 mL of dry THF was added  n-butyllithium (0.205 mmol) i n hexane.  After the  a  reaction  mixture had been s t i r r e d at -78°C for 10 min, iodobutane  (-3.5  added  1 h and at room  and  the  solution  temperature for 7 h. of  the  was  stirred  at  -78°C  Normal workup, followed by  for column  mmol) was  chromatography  residual o i l on s i l i c a gel (10 g, e l u t i o n with petroleum ether-  d i e t h y l ether; 4:1)  and d i s t i l l a t i o n (air-bath temperature  90-93°C/0.05  - 263 Torr) of the o i l thus obtained, afforded 30 mg (65%) of the diene (255). This c o l o r l e s s o i l exhibited i r (film): 3076, 1636, 911 cm" ; H nmr (400 MHz, CDC1 ) 6: 0.91 1  X  3  Hz) 0.99 2.07  (t,  2  2  - 7.5 Hz), 2.88 -OMe)  (dt,  Hz),  2  5.00  6 Hz).  (broad t,  2H,  (s,  (m,  2H),  3.69-3.76  2H, -CH OCH 0-), 4.97 2  2  Exact Mass c a l c d .  for  C H iO 1 2  2  2  7.5  CH3CH2CH2CH2-),  Hz),  , J  2H),  3.40  (s,  (s,  2H,  4.05  (ddt, IH, Hg, J - 10,  (ddt, IH, H , J - 17, 2, 1 Hz), 5.78 A  (m,  2  CH3CH2CH2CH2-  2H, b i s - a l l y l i c protons, J - 6, 1  3.55-3.60  -CH OCH 0-), 4.71 2  2  3  3  1200-993 (br),  3H, CH3CH CH CH -, J -  3H, - C H C H , J - 7.5 Hz), 1.27-1.40 (m, 4H,  (q, 2H, - C H C H , J - 7.5 Hz), 2.12  3H,  (t,  1457,  2,  (ddt, IH, H , J - 17, c  (M+'C^Ho^):  181.1593;  1 10,  found:  181.1597.  Preparation of 1,4-decadiene  Following  (Z)-10-chloro-5-ethyl-4-(2-methoxyethoxy)methoxvmethyl(258)  general  of the iodide (221) solution  of  procedure 7, to a cold ( - 7 8 ° C ) , s t i r r e d solution  (56 mg, 0.1647 mmol) i n 5 mL of dry THF was added  n-butyllithium (0.362 mmol) i n hexane.  After the reaction  had been s t i r r e d at -78°C for 10 min, 5-chloro-l-iodopentane was  added  and  the  temperature for 6 h.  solution  a  (-3.5 mmol)  was s t i r r e d at -78°C for 2 h and at room  Glc analysis of an aliquot of the  crude  solution  - 264 indicated that i t contained a 9:1 mixture of (258) trisubstituted moiety. afforded  alkene  the place of the  (Cl^^Cl  Normal workup, followed by careful d i s t i l l a t i o n of the  mixture  38  mg  having  a  proton  (72%) of the chloro diene (258)  130-135°C/0.05 Torr).  This colorless  1637,  cm" ;  1200-960  in  and the corresponding  (br)  oil  3-H nmr  1  (air-bath temperature  exhibited  (400  ir  (film):  MHz, CDC1 ) 6: 0.99  2  3  E  Hz), 2.88 -OMe),  (dt,  3.53  2H), 4.04 Hg,  J  2  2H,  2  5.00  4.71  (s,  3 5  2 2  3.40  2  (s,  3H,  3.69-3.76 (m,  2H, -CH OCH 0-), 4.97  In a decoupling  (dd, J = 17,  ( M - C H 0 ) : 229.1359;  2  experiment  (ddt, IH, (ddt,  irradiation  I r r a d i a t i o n of the  +  4  9  2  10  general  signal  (dd, J - 10, 2 Hz), S 5.00 Hz).  of  Exact  Mass  at  S  (dd, J  calcd.  for  found: 229.1365.  Preparation of (Z)-5-ethvl-4-vinvl-l.4-nonadiene  Following  H  6 1.79 collapsed the t r i p l e t at S 3.53 to a s i n g l e t and  at  = 17, 2 Hz) and 5 5.78 1 3  2H, H , J - 7  A  s i m p l i f i e d the signals at S 4.97  C H 0 C1  Hz),  2H,  (ddt, IH, H , J - 17, 2, 1 Hz), 5.78  altered the multiplet at 6 1.24-1.40. 2.88  1  D  2  - 10, 2, 1 Hz),  6,  (t,  H , J = 7 Hz), 3.56-3.61 (m, 2H),  2H, -CH OCH 0-),  signal  3  2H, b i s - a l l y l i c protons, J •= (t,  (s,  (q, 2H, - C H C H , J - 7.5 Hz), 2.13  IH, E Q , J •= 17, 10, 6 Hz). the  (quintet,  G  H , J - 7 Hz), 2.07  (t, 3H,  3  - C H C H , J - 7.5 Hz), 1.24-1.40 (m, 4H, Hp and H ) , 1.79  3080,  (259)  procedure 7, to a cold ( - 7 8 ° C ) , s t i r r e d solution  - 265 of  the iodide (227)  (52 mg, 0.2096 mmol) i n 5 mL of dry THF was added a  solution of n-butyllithium (0.2516 mmol) i n hexane.  After the  mixture had been s t i r r e d at -78°C for 10 min, iodobutane added and the solution was  room  Normal workup, followed by d i s t i l l a t i o n  (air-  bath temperature 90°C/20 Torr) of the residual o i l afforded 20 mg  (54%)  of  the  1675,  for  30 min.  triene  1626,  (259).  1458,  -CH2CH2CH2CH3,  This  Hz), 1.5  2  4.96  1.00  J  -  17,  10  (t,  6:  2  3.01  (dt,  3  2, 1.5 Hz), 4.98  (ddt, IH, H , J - 17, 10, c  (t,  3H,  (t,  2H,  2H, b i s - a l l y l i c protons, J - 6, (dd, IH, H , J  A  Hz).  0.92  3083,  3  D  (ddt, IH, H , J — 17, 2, 1.5 Hz), 5.14  5.83  and  3H, - C H C H , J - 7.5 Hz), 1.26-1.44 2  B  17, 1.5 Hz),  h  (q, 2H, - C H C H , J - 7.5 Hz), 2.19  (ddt, IH, H , J - 10,  Hz),- 4.99  2  colorless o i l exhibited i r (film): 3  J - 7 Hz)  3  for  1  (m, 4H, -CH2CH2CH2CH3), 2.02 2  -78°C  895 c m ' ; *H nmr (400 MHz, CDC1 )  J - 7 Hz),  -CH CH CH2CH ,  at  mmol) was at  temperature  stirred  (-2.5  reaction  6 Hz),  =  1.5 10,  (dd, IH, H , J = E  6.73  (dd,  IH,  Hp,  Exact Mass calcd. for C H 2 (M+) : 178.1721; found: 13  2  178.1719.  Preparation of (Z)-5-(3-butenvl)-4-vinvl-l.4.9-decatriene  Following general procedure 7, to a cold ( - 7 8 ° C ) , of  the iodide (230)  (260)  stirred  solution  (99 mg, 0.3613 mmol) i n 8 mL of dry THF was added a  - 266 solution  of  n-butyllithium  (0.794 mmol) i n hexane.  had been s t i r r e d at -78°C for 10 min, added  and  the  solution  temperature for 4 h. aliquot  of  the  was  5-iodo-l-pentene  stirred  in  the  place  by  glc  analysis  of  and the  the 4-pentenyl moiety.  material  Careful  of the pentaene (260).  3078, 1640,  1465,  991,  911 c m ' ; tt nmr (400 MHz, CDC1 ) 1  5.91  3  (diffuse m, 3H),  Mass c a l c d . for C H 4 (M+) : 1 6  2  General procedure 8:  an  with  afforded,  6:  l  - 6, 1 Hz), 4.93-5.11 (diffuse m, 7H), -  of  This colorless o i l exhibited i r  (m, 2H), 2.03-2.37 (diffuse m, 8H), 3.02  5.76  was  6.71  (dt, 5.17  52  (film):  1.46-1.57  2H, b i s - a l l y l i c protons, J (dd, IH, H , J = 17, 1 Hz), E  (dd, IH, Hp, J - 17, 10 Hz).  216.1878;  a  distillation  (air-bath temperature 7 0 - 7 5 ° C / 0 . 0 5 Torr) of the crude o i l mg (67%)  mmol)  mixture indicated that the l a t t e r material con-  s i s t e d of a 9:1 mixture of the pentaene (260) proton  (-7  at -78°C for 10 min and at room  Normal workup, followed  crude  After the mixture  Exact  found: 216.1885.  Preparation of vinylcopper (I)  reagents and t h e i r  reaction with electrophiles  To a cold ( - 7 8 ° C ) , (1  equiv)  s t i r r e d solution of the appropriate v i n y l  i n dry THF (-30 mL per mmol) was added a solution of n - b u t y l -  l i t h i u m (2.1 equiv) i n hexane. -78°C  iodide  for 10-15 min.  The r e s u l t i n g solution  was  stirred  Cuprous(I) bromide*dimethyl sulphide complex  equiv) was added and the solution was s t i r r e d at -48°C An excess of the appropriate e l e c t r o p h i l e ,  for  20-30  at (1.1  min.  which had been passed through  basic alumina was added, and the mixture was s t i r r e d at -48°C for  45-60  -  267  -  min.  S a t u r a t e d aqueous ammonium c h l o r i d e (pH 8,  ether  (-20  2 mL/mmol) and  diethyl  mL/mmol) were added and the mixture was v i g o r o u s l y s t i r r e d  room temperature  until  a b l u e aqueous s o l u t i o n was e v i d e n t .  at  The o r g a n i c  s o l u t i o n was washed t h r e e times w i t h s a t u r a t e d aqueous ammonium c h l o r i d e (pH 8 ) , crude  d r i e d o v e r anhydrous magnesium s u l f a t e  and  concentrated.  The  p r o d u c t was chromatographed on s i l i c a g e l ( e l u t i o n w i t h p e t r o l e u m  ether-diethyl  e t h e r ) and the r e s u l t i n g o i l was d i s t i l l e d , a f f o r d i n g pure  product.  Preparation of  (E)-4-(2-methoxvethoxy)rnethoxvniethvl-5-isopropvl-7-  methvl-1.4.7-octatriene  Following o f the  general  i o d i d e (223)  solution  of  n butyllithium _  at  sulfide  (35  added  procedure 8,  complex  to a c o l d ( - 7 8 ° C ) ,  (54 mg, 0.1525 mmol)  had been s t i r r e d  s t i r r e d at  (264)  (0.38  -78°C  for  mg,  0.167  - 4 8 ° C f o r 30 m i n .  i n hexane.  min,  mmol)  After  cuprous(I)  the  bromide•dimethyl  (-1.5  - 4 8 ° C f o r 45 m i n .  mmol)  elution  with  petroleum  ether-diethyl  ether;  4:1)  was  Normal workup,  f o l l o w e d by column chromatography o f the r e s i d u a l o i l on s i l i c a g,  mixture  was added and the s o l u t i o n was  3-Iodo-2-methylpropene  and the s o l u t i o n was s t i r r e d a t  solution  i n 5 mL o f dry THF was added a  mmol)  10  stirred  gel  (5  and d i s t i l l a t i o n  - 268 (air-bath temperature 8 8 - 9 2 ° C / 0 . 0 5 afforded ir  Torr)  of  33 mg (77%) of the triene (264)^  the  oil  6:  3  0.93  (d,  6H,  (CH ) CH-, 3  J. -  2  methyl), 2.72 ( b r o a d s , 2H, b i s - a l l y l i c (CH ) CH-, 3  J  2  -  7  Hz),  obtained,  This colorless o i l exhibited  ( f i l m ) : 3080, 1651, 1637, 1171 - 1045 (br), 900;  CDC1 )  thus  X  H nmr  (400 MHz,  7 Hz), 1.75 (s, 3H, v i n y l  protons),  2.91  (septet,  IH,  2.97 (broad d, 2H, b i s - a l l y l i c protons, J_ - 6  Hz),  3.39 (s, 3H, -OMe), 3.53-3.58 (m, 2H), 3.66-3.73 (m, 2H), 3.93  2H,  -CH OCH 0-), 4.55 (d, IH, H , J - 0.5 Hz), 4.67 (s, 2H, -CH OCH 0-) 2  2  D  4.73 (d, IH, H , J - 0.5 Hz), D  (ddt,  IH,  2  B  H , J - 17, 2, 1 Hz), 5.83 (ddt, IH, H , J - 17, 10, 6 Hz). A  c  +  1 3  Preparation of  Following  2 1  4  9  2  193.1592;  found  general  (265)  procedure 8, to a cold ( - 7 8 ° C ) , s t i r r e d solution  of the Iodide (223) (62 mg, 0.175 mmol) i n 5 mL of dry THF was jj-butyllithium  had been s t i r r e d sulphide  193.1587.  (E)-7-bromo-4-(2-methoxvethoxy)methoxvmethvl-5-iso-  propyl-1.4.7-octatriene  of  2  4.99 (ddt, IH, H , J - 10, 2, 1 Hz), 5.05  Exact Mass c a l c d . for C H 0 ( M - C H 0 ) :  solution  (s,  complex  at (39  -78°C  (0.437 mmol) i n hexane. for  mg, 0.192  s t i r r e d at -48°C for 30 min.  10  min,  cuprous(I)  added  a  After the mixture bromide*dimethyl  mmol) was added and the solution was  2,3-Dibromopropene (-1.75 mmol) was  added  - 269 -  and the s o l u t i o n was s t i r r e d at -48°C for 1 h. by  column  elution  chromatography  with  (air-bath  petroleum  temperature  of  the  residual  ether-diethyl 96-100°C/0.05  (film):  CDC1 )  3078,  6: 0.98  3  1634,  (d,  6H,  Torr)  1200-1039 3  ( C H ) C H - , J - 7 Hz), 2.93 3  3.23  2H, b i s - a l l y l i c protons,  2  H , A  5.01  2  J  -  1 8  Preparation of  7  of  H nmr (400 MHz,  2.93  (septet,  -  1  Hz), (s,  3.41  D  -  (M -C H 0 ): +  4  9  2  17,  10,  257.0542;  (s, 2  5.06  6.5  Hz).  -OMe), 4.68  2  1 Hz), 5.50  1 Hz),  3H,  2H, -CH 0CH 0-),  IH,  (ddt, (dt,  (s, IH,  IH, H ,  Exact  D  Mass  found: 257.0543.  (266)  general  of the iodide (221) solution  Hz),  X  exhibited  (Z)-5-ethvl-4-(2-methoxyethoxy)methoxvmethyl-7-methyl-  1.4.7-octatriene  Following  1  (dt, IH, H , 1 - 2 , c  7 9  1 2  910 cm" ;  B  (ddt, IH, H , J  c a l c d . for C H 0 B r  the o i l thus obtained,  (ddt, IH, H , J - 10, 2, 1 Hz),  J - 17, 2, 1 Hz), 5.45  J - 2, 1 Hz), 5.79  distillation  This colorless o i l  3.55-3.61 (m, 2H), 3.68-3.74 (m, 2H), 3.97 2H, -CH OCH 0-),  and  (dt, 2H, b i s - a l l y l i c protons, J - 6.5,  2  (t,  J  2  followed  on s i l i c a gel (10 g,  4:1)  of  (br),  (CH ) CH-  oil  ether;  afforded 42 mg (70%) of the triene (265). ir  Normal workup,  procedure 8, to a cold ( - 7 8 ° C ) , s t i r r e d solution  (61 mg, 0.1794 mmol) i n 5 mL of dry THF was added  n-butyllithium  had been s t i r r e d  at  -78°C  (0.448 mmol) i n hexane. for  10  min,  cuprous(I)  a  After the mixture bromide.dimethyl  - 270 sulphide  complex  (40  mg,  0.1974 mmol) was added and the solution was  s o l u t i o n of n-butyllithium (0.448 mmol) i n hexane. had  been  stirred  at  -78°C  for  10  at  -48°C  for 25 min.  3-Iodopropene  the s o l u t i o n was s t i r r e d at -48°C for 1 h. column  chromatography  110°C/0.05  0.98 2H,  1637, (t,  1456,  ether;  Torr)  (69%) of the triene (266). 3078,  This  (ddt, 5.79  IH,  H , B  (s,  (s,  (s,  2  4  9  2  Preparation of  found:  3H, 2  (air-bath  ir  methyl),  (film):  -OMe),  2  2.07  2.94  (q,  (dt, 2H,  3.54-3.61  (m,  (d, IH, H , J -  (d, IH, H , J — 0.5 D  = 10, 2, 1 Hz), 5.03  179.1435;  3H, v i n y l  (s,  2  c  +  elution  X  2H, -CH OCH 0-), 4.64  (ddt, IH, H , J = 17, 10, 6 Hz).  (M -C H 0 ):  exhibited  2H, b i s - a l l y l i c protons),  2H, -CH 0CH 0-), 4.75 J  by  3  (m, 2H), 4.03  (s,  followed  distillation  oil 1  3  0.5 Hz), 4.70  was  (~3.5 mmol) was added and  and  colorless  3  3.69-3.75  solution  Normal workup,  7:3)  b i s - a l l y l i c protons, J = 6, 1 Hz), 3.40 2H),  the  1201-960 (br), 852 cm" ; H nmr (400 MHz, CDC1 ) 6:  - C H C H , J = 7 Hz), 2.85 2  and  of the o i l thus obtained, afforded 33 mg  3H, - C H C H , J = 7 Hz), 1.69 2  mixture  of the residual o i l on s i l i c a gel (10 g,  with petroleum ether-diethyl temperature  the  min, cuprous(I)• bromide dimethyl  sulphide complex (40 mg, 0.1974 mmol) was added stirred  After  D  Hz),  5.00  (ddt, IH, H , J - 17, 2, 1 Hz),  Exact  A  Mass  calcd.  for  C H 0 1 2  179.1435.  (Z)-7-bromo-5-ethyl-4-(2-methoxvethoxv)methoxymethyl-  1 9  - 271 Following general procedure 8, to a cold ( - 7 8 ° C ) , of  the  iodide (221)  at  -78°C  for  10  min,  After  cuprous(I)  the  mixture  for  30  min.  2,3-Dibromopropene  s o l u t i o n was s t i r r e d at -48°C for column  chromatography  1.00  1635, (t,  (dt,  ether;  1454,  This  2  Hz), 5.56 Exact  followed  distillation  2  5.07  1  3  X  exhibited  ir  Mass  243.0391.  by  elution  3  2  (broad s,  4.69  (s,  2H,-CH OCH 0-), 5.02 2  2  A  IH, H , J - 1.5, D  calcd.  for  1 Hz), 5.79  C H 0 Br 7 9  1 1  1 6  (film):  H nmr (400 MHz, CDC1 ) 6:  (q, 2H, - C H C H , J = 8  (ddt, IH, H , J •= 17, 2, 1 Hz), 5.45  (dt,  at  (air-bath  3  Hz),  2.94  2H, b i s - a l l y l i c protons),  3H, -OMe), 3.55-3.61 (m, 2H), 3.69-3.75 (m, 2H), 4.05  -CH 0CH 0-), 2  stirred  was added and the  workup,  oil  1200-960 (br), 914 c m ' ;  3H, - C H C H , J - 8 Hz), 2.12  (s,  and  colorless  2H, b i s - a l l y l i c protons), 3.31  3.41  mmol)  Normal  4:1)  been  9 4 - 9 7 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 44 mg  (78%) of the triene (267). 3077,  h.  (~4  was  of the residual o i l on s i l i c a gel (10 g,  with petroleum ether-diethyl temperature  1  had  bromide•dimethyl sulphide  complex (38 mg, 0.187 mmol) was added and the solution -48°C  solution  (58 mg, 0.170 mmol) -in 5 mL of dry THF was added a  s o l u t i o n of n-butyllithium (0.421 mmol). stirred  stirred  (s,  2H,  (ddt, IH, Hg, J - 10, 2, 1 (d, IH, H , J - 1.5 D  Hz),  (ddt, IH, H , J - 17, 10, 6 Hz). c  (M+'C^HoO^:  243.0384;  found:  - 272 Preparation of (Z)-7-bromo-5-ethyl-4-vinyl-l.4.7-octatriene  (268)  H  Following general procedure 8, to a cold ( - 7 8 ° C ) , of  the  (227)  iodide  had  been  stirred  dimethyl sulphide complex solution  was  stirred  at (38  at  -78°C mg,  -48°C  for  After the reaction  10 min, cuprous(I) bromide-  0.1859  mmol)  for 20 min.  was  added  temperature  petroleum  ether)  (film):  3084, 1676,  1458,  2  and  This 1  (air-bath  (q, 2H, -Cfi CH , J - 7.5 Hz), 2  1 Hz), 5.83  17, 10 Hz).  3  (t,  ir (t,  D  G  1 Hz), 5.54  (dt,  (ddt, IH, H , J_ - 17, 10, 6 Hz), 6.61 c  A  (dd, IH, H , J E  IH,  H , G  J  -  (dd, IH, Hp, J -  In a decoupling experiment i r r a d i a t i o n of the s i g n a l  s i m p l i f i e d the signals at 6 5.00  (dt,  (ddt, IH, H , J  (ddt, IH, H , J - 10, 1 Hz), 5.23 IH, H , J - 1.5,  3.07  2H, b j ^ - a l l y l i c proton,  B  (dt,  exhibited  X  (ddt, IH, H , J_ - 10, 2, 1.5 Hz), 5.05  17, 2, 1.5 Hz), 5.08 17, 1 Hz), 5.45  oil 3  3  J_ - 1.5 Hz), 5.00  3,07  distillation  colorless  b i s - a l l y l i c protons, J - 6, 1 Hz), 3.36  1.5,  Normal  909 cm" ; H nmr (400 MHz, CDC1 ) 6: 1.01  3H, - C H C H , J - 7.5 Hz), 2.18  -  h.  (-3.5  1 3 0 - 1 3 5 ° C / 2 0 Torr) of the o i l thus obtained, afforded 30 mg  (74%) of the bromo tetraene (268).  -  the  followed by column chromatography of the residual o i l on s i l i c a  gel (10 g, e l u t i o n with  2H,  and  2,3-Dibromopropene  mmol) was added and the solution was s t i r r e d at -48°C for 1 workup,  solution  (42 mg, 0.169 mmol) i n 5 mL of dry THF was added  n - b u t y l l i t h i u m (0.372 mmol) as a solution i n hexane. mixture  stirred  (dd, J - 10, 2 Hz), 6 5.05  at  6  (dd, J  - 273 -  -  17, 2 Hz), and 6 5.83  at  6  3.36  (dd, J - 17, 10 Hz).  I r r a d i a t i o n of the  s i m p l i f i e d the signals at 6 5.45  (d, J - 1.5 Hz).  Exact Mass c a l c d .  for  C  (d, J - 1.5 Hz) and S 5.54 H  1 2  signal  17°  '•  7 9 B r  240.0514;  found: 240.0516.  Preparation of the ketone  To  a  cold  (-78°C),  (270)  s t i r r e d solution of the iodide (221)  0.332 mmol) i n 4 mL of dry THF was added a (0.731  mmol) i n hexane.  solution  and  the  solution  n-butyllithium  After the reaction mixture had been s t i r r e d at  -78°C for 10 min, magnesium bromide etherate (103 mg, added  of  0.398  was s t i r r e d at -78°C for 10 min.  mmol)  -48°C  for  Copper(I) bromide.dimethyl sulphide complex (17 mg, 0.08 mmol),  2-cyclohexen-l-ene (34 pL, 0.349 mmol) and (46  was  Dry diethyl  ether (8 mL) was added and the white solution was s t i r r e d at 10 min.  (113 mg,  boron  trifluoride  etherate  ftL, 0.36 mmol) were added and the lime colored solution was s t i r r e d  at -78"C for 3 h .  Saturated aqueous ammonium chloride (pH 8,  -1.0  mL)  was added and the solution was allowed to warm to room temperature.  The  organic s o l u t i o n was washed three times with saturated aqueous chloride trated.  (pH  8),  dried  over  ammonium  anhydrous magnesium sulfate and concen-  Column chromatography of the residual o i l on s i l i c a gel (15  g,  - 274 elution  with  petroleum  ether-diethyl  ether;  (air-bath temperature 1 4 5 - 1 5 0 ° C / 0 . 0 5 Torr) of afforded  70  mg  (68%)  of  the  ketone  1:1) the  and  oil  (270).  distillation  thus  This  obtained,  pale yellow o i l  exhibited i r (film): 3076, 1714, 1636, 1106, 1045, 913 cm" ; H nmr (400 1  MHz,  CDC1 )  6:  3  1.04  X  (t, 3H, - C H C H , J *= 7.5 Hz), 1.64-1.78 (m, 3H), 2  3  2.11 (q, 2H, - C H C H , J = 7.5 Hz), 2.07-2.17 (m, IH), 2.22-2.32 (m, 2H), 2  2.35-2.44  (m,  3  2H),  2.91  (dt,  2H, b i s - a l l y l i c protons, J - 6, 1 Hz),  3.04-3.12 (m, IH), 3.38 (s, 3H, -OMe), 3.51-3.58 3.62-3.73  (m,  -CH OCH 0-), 2  for  2, C  1 8  2  2  2  O  4  (M+):  mmol)  in  (271)  10  the  iodide  (223)  (79 mg,  2 mL of dry THF was added a s o l u t i o n of n-butyllithium  (0.468 mmol) i n hexane. for  Exact Mass c a l c d .  310.2144; found: 310.2142.  To a cold ( - 7 8 ° C ) , s t i r r e d solution of  -78°C  2  A  Preparation of the ketone  0.223  2  2  c  3 0  -0CH CH 0-),  -OCH CH 0-), 4.04 (s, 2H, -CH OCH 0-), 4.68 (s, 2H,  1 Hz), 5.78 (ddt, IH, H , J <= 17, 10, 6 Hz). H  2H,  5.00 (ddt, IH, Hg, J = 10, 2, 1 Hz), 5.01 (ddt, IH, H , J =  2  17,  2H,  (m,  min,  After the reaction mixture had been s t i r r e d  at  magnesium bromide etherate (63 mg, 0.245 mmol) was  added and the s o l u t i o n was s t i r r e d  at  -48°C  for  10  min.  Copper(I)  - 275 bromide-dimethyl sulphide  complex  en-l-one  mmol)  (23  /iL,  0.234  (11  for 3 h.  colored  trated.  dried over  anhydrous  to  room  magnesium  with  petroleum  temperature  ether-diethyl 150°C/0.05  ether;  Torr)  of  afforded 22 mg (31%) of the ketone (271). (film):  3077,  CDC1 ) 6: 1.04  (t,  3  7  solution  was  stirred  at  temperature.  The  sulfate  and  concen-  Column chromatography of the residual o i l on s i l i c a gel (10 g,  (air-bath  ir  2-cyclohex-  solution was washed three times with saturated aqueous ammonium  chloride (pH 8),  elution  mmol),  Saturated aqueous ammonium chloride (pH 8, -1.0 mL) was  added and the solution was allowed to warm organic  0.055  and boron t r i f l u o r i d e etherate (30 /iL,  0.245 mmol) were added and the lime -78°C  mg,  1713,  1637,  1106,  3H, (CH ) CH-, 3  2  1:1) oil  distillation  thus  obtained,  This colorless o i l  exhibited  1045,  the  and  912 c m ; ti nmr (400 MHz, - 1  J = 7 Hz), 1.07  l  (d, 3H, ( C H ) C H - , J = 3  2  Hz), 1.60-1.93 (diffuse m , 3 H ) , 2.04-2.14 (m, IH), 2.26-2.37 (m, 2H),  2.37-2.45 (m, 2H), 2.57 2.96  (broad  (broad t,  IH, J - 12  4.17  2.69-2.82  d, 2H, b i s - a l l y l i c protons, J - 6 Hz), 3.38  3.52-3.58 (m, 2H), 3.66-3.74 (m, 2H), 4.06 Hz),  Hz),  (d,  IH,  -CH OCH 0-, 2  J  2  4.97-5.05 (m, 2H, H and H ) , 5.77 A  Exact Mass c a l c d . for C  1 5  H  2 3  0  •= 9 Hz), 4.71  (ddt,  B  IH, H , J c  (M -C H 0 ): +  2  (d, IH,  4  9  2  (s,  (m,  3H, -OMe),  -CH OCH 0-, 2  (s, -  2H),  J  2  =  9  2H, -CH OCH 0-), 2  17,  10,  2  6  Hz).  235.1697; found: 235.1697.  - 276 VIII.  Synthesis and chemistry of a l k y l  (E)-2-(tri-n-butylstannyl)-3-  trimethylgermyl-2-alkenoates and a l k y l ( Z ) - 3 - ( t r i - n - b u t y l stannyl) -2-trimethylgermyl-2-alkenoates  General Procedure 9:  Preparation of compounds (277)  Me Ge 3  H  R  (277)  C0 R'  Bu Sn  SnBu  R  2  277  3  3  and (278)  and (278)  GeMe  H 278  C0 R" 2  To a one necked, round bottomed flask attached to added  the  appropriate  trimethylgermane (276) The  mixture  was  3  a  condensor  was  acetylenic ester (1 equiv), t r i - n - b u t y l s t a n n y l (1.0-1.5 equiv) and (PPt^^Pd (0.02-0.06  heated  to  8 0 - 1 0 0 ° C for 5-24 h.  crude black o i l indicated the presence of  the  equiv).  T i c analysis of the  reagent  (276)  and  two  products which were r e a d i l y separated by column chromatography on s i l i c a gel (elution with petroleum ether-diethyl ether). of  the  After  concentration  appropriate f r a c t i o n s , the (E) and (Z) isomers (277)  and (278),  respectively and the recovered tri-n-butylstannyltrimethylgermane  (276)  were subjected to a vacuum of 0.05 Torr for 1-2 h at room temperature.  Preparation of tri-n-butvlstannvltrimethylgermane  D-Bu SnGeMe 3  (276)  3  To a c o l d ( 0 ° C ) , s t i r r e d solution of lithium diisopropylamide (20.16 mmol) i n 75 mL of dry THF was added a  solution  of  tri-n-butylstannane  - 277 (4.48 g, 19.2 mmol) i n 10 mL of dry THF. been s t i r r e d at 0°C for 15 min  After the reaction mixture had  bromo-trimethylgermane  (3.98  g,  20.16  mmol) was added and the colorless solution was s t i r r e d at 0°C for 15 min and at room temperature for 15 min. trated,  petroleum  ether  (100  After the solution had been concen-  mL)  was  added  to the residue and the  r e s u l t i n g suspension was passed through a short column of g, e l u t i o n with petroleum ether).  Florisil  Concentration of the eluate,  by d i s t i l l a t i o n (air-bath temperature 1 1 0 ° C / 0 . 0 5 Torr) of oil,  afforded  4.215  less o i l exhibited i r (film): 2960, 2930, 823 c m ; - 1  CDC1 )  6:  3  Hz),  0.90  0.32 (t,  (s,  2  2  8  7  6H, (CH CH CH CH ) Sn-, J 3  (CH CH CH CH ) Sn-, 3  9H, -GeMe.3), ° -  2  3  J  2  -  2  2  3  +  15  butenoate (279) 2-butenoate  -  H  residual  This color-  nmr  (270 MHz,  >  (CH CH CH CH ) Sn-, J = 8  8  Hz),  3  8 Hz), 1.40-1.53 (m, 6H,  Exact Mass c a l c d . for C H3gGeSn (M ):  Preparation of ethyl  9H  X  followed  the  g (89%) of the stannylgermane (276).  (20  408.1060;  2  2  2  1.28  3  (sextet,  6H,  (CH CH CH CH ) Sn-). 3  2  2  2  3  found: 408.1063.  (E)-2-(tri-n-butylstannyl)-3-trimethylgermvl-2-  and ethyl (Z)-3-(tri-n-butvlstannvl)-2-trimethylgermyl-  (280)  Me Ge  C0 Et  3  2  SnBu  Me  279  3  Bu Sn  GeMe  Me  C0 Et  3  3  2  280  Following general procedure 9, to a s t i r r e d mixture of ethyl 2-buty noate (276)  (70)  (71  mg, 0.634 mmol) and tri-s-butylstannyltrimethylgermane  (0.653 mmol) was added (PPb^^Pd (0.021 mmol) and the mixture  was  - 278 stirred  at  85"C for  24 h.  s i l i c a gel (20 g, e l u t i o n afforded  (276)  Column chromatography of the black o i l on  with  petroleum  ether-diethyl  ether;  17:1)  and the esters (279) and (280) as clear colorless  oils.  Subjection of each of the three o i l s to vacuum (0.1 Torr, -1 h) afforded 176 mg (61%) of (279), 53 mg (19%) of (280) and 60 mg (22%) of recovered (276). l  tt  Compound (279) exhibited i r (film): 1704, 1207, 1042, 829 c m ' ; 1  nmr  (270  MHz, CDC1 )  6:  3  0.24  (s,  9H,  -GeMe.3),  0.87 (t, 9H,  (CH (CH )3)3Sn-, J - 7 Hz), 0.92-1.02 (m, 6H, (CH CH CH CH ) Sn-) , 3  2  (t,  3  3H,  -OCH CH ), 2  1.40-1.58 -  10  6:  J  3  2  3  2  2  2  -0.5 (q), 11.6 (t, "  5  0  Hz  >>  2  3  2  2  2  60.1 ( t ) , 146.0 (s), 20 41°2 H  -  2  <t.  161.3  3j  1 3  3  -Sn-C "  (s),  6  0  H z  172.5  ( M - C H ) : 505.1350;  G e S n  3  J  4  3  >.  2  8  (s).  •  S n  -H  C nmr (75.6 MHz, CDCI3)  - 326 Hz), 13.6 (q), 14.2  7  1.27  3  (m, 6H, (CH CH CH CH ) Sn-), 1.95 (s, 3H, v i n y l methyl, 2  -Sn-C  2  (m, 6H, (CH CH CH CH ) Sn-),  Hz), 4.08 (q, 2H, -OCH CH , J - 7 Hz);  3j  c  - 7 Hz), 1.20-1.39  2  9  2j  (q) ,  26.6  -Sn-C "  Exact  Mass  2  0  Hz  (q,  >-  calcd.  for  found: 505.1357.  +  3  Compound (280) exhibited i r (film): 1709, 1560, 1206, 828, 735 c m ' ; 1  MHz, CDCI3)  H nmr (270  l  (CH (CH ) ) Sn-, 3  (t,  2  3  8:  9H,  3  1.23-1.40  (m,  3  2  2  2  2j  0.1  -Sn-C "  60.0  2  (q), 4  (t), 41  2  2  6H,  2  2  ( «  0  t  8  H z  >.  9H  11.3 2  149.8  7  -  4  (t, <t.  (s),  3j  -Sn-C "  155.6  6  3 2  2  (s),  1 3  >  1.29  3  (CH CH CH CH ) Sn-), 3  2  3  3  C H O G e S n (M+-CH3): 505.1349; 20  9  2  (m, 6H, (CH CH CH CH ) Sn-), 2.01 (s, 3H, v i n y l methyl,  - 40 Hz), 4.17 (q, 2H, -OCH CH , J - 7 Hz); 8:  °-  -GeMe.3), 3  3H, -OCH CH ), J - 7 Hz),  1.40-1.57  (s,  J - 7 Hz), 0.92-1.00 (m, 6H, (CH CH CH CH ) Sn-),  3  2  0.30  2  3  3  J  S  n  .  H  MHz, CDCI3)  C nmr (75.6  0 Hz), 13.6 (q), 14.5 (q), 26.7 (q, Hz  > > 29.1 (t, 171.8  (s).  found: 505.1342.  2  J  S  n  .  c  -  19 Hz),  Exact Mass c a l c d . for  - 279  Preparation  o f methvl  -  (E)-4-methyl-2-(tri-n-butylstannyl')-3-trimethvl-  germvl-2-pentenoate (281)  and methyl  (Z)-4-methyl-3-(tri-n-butvl-  stannvl)-2-trimethylgermvl-2-pentenoate  (282)  282 Following  g e n e r a l procedure  9,  to  4-methyl-2-pentynoate  (115)  t rime thy 1 germane (276)  (0.557 mmol) was  and  the m i x t u r e was  (65 mg,  ether;  49:1)  afforded  as c l e a r c o l o r l e s s o i l s . vacuum (282) ir  (0.1 and  of recovered  ( f i l m ) : 1711,  1555,  1203,  -GeMe ), 0.90  1.32  ( s e x t e t , 6H,  3  2  2  2  -OMe); a  2  2  2  of mg  cm ; -1  X  H  2  1.12  3  3  2  2  2.34  (d,  at  S  the  o f (281),  Compound  J  6H, -  8  -  41 mg  (281)  (400 MHz, 7  Hz),  4  J.Sn-H  ~  9  ((CH ) CH-) 3  2  and  S  Hz;  to  (15%)  of  0.33  3  Hz),  2  0.93-1.00  J  -  1.44-1.54 3.64  I n a nOe  (-OMe).  7 Hz), (m, (s, (5  6H, 3H, 2.34)  difference  (-GeMe.3) caused 3.64  oils  exhibited  (d) caused c o l l a p s e o f the s e p t e t that  (282)  CDC1 ) 6:  (CH ) CH-, 3  ether-  and  three  2  showed  1.12  petroleum  (48%)  experiment, i r r a d i a t i o n o f the s i n g l e t a t 6 0.33 enhancement  with  of  nmr  mmol)  Column chromatography  each  3  3  methyl  (0.026  ( s e p t e t , IH, Me CH-, J - 7 Hz),  I r r a d i a t i o n a t 6 1.12 and  2  of  the e s t e r s (281)  (276).  (CH CH CH CH ) Sn-, J  3  singlet  and  (CH3(CH )3) Sn-,  (CH CH CH CH ) Sn-),  (CH CH CH CH ) Sn-), 3  833  ( t , 9H,  3  6H,  to  Subjection  (27%)  (m,  (PPl^^Pd  elution  (276)  mixture  mmol) and t r i - n - b u t y l s t a n n y l added  g,  mg  (s, 9H,  0.515  T o r r , -1 h) a f f o r d e d 132  61.5  stirred  s t i r r e d a t 86-90°C f o r 24 h.  o f the b l a c k o i l on s i l i c a g e l (20 diethyl  a  signal  Similarly,  - 280 i r r a d i a t i o n of the s i n g l e t at S 3.64 6 -  0.33  (-GeMe );  325 Hz), 13.6  -  20  Hz),  173.1  (q),  44.6  (s).  found:  22.0  (d,  3  Exact Mass  MHz, CDCI3) 5:  (q), J  S  .  n  27.3  (t,  3  J  S n  2.6  -C "  - 52 Hz), 50.8  c  calcd.  for  (q),  6 2  Hz  (q),  2 1  4 3  >•  2 8  145.0  C H 0 GeSn  (t, ^ s n - c  11.6 -  9  2  (s),  166.9  (M+-CH3):  2  Isn-C (s),  519.1506;  519.1497.  Compound nmr  C nmr (75.6  1 3  3  (-OMe) caused signal enhancement at  (400  (282)  MHz,  exhibited i r (film): 1714,  CDCI3)  6:  0.32  (s,  1542,  9H,  1197,  830 c m ; - 1  -GeMe ),  X  0.91(t,  3  H  9H,  (CH (CH )3)3Sn-, J = 7 Hz), 1.00  (d, 6H, ( C H ) C H - , J - 7 Hz), 0.97-1.05  (m, 6H, (CH CH CH CH ) Sn), 1.34  (sextet, 6H, (CH CH CH CH ) Sn-, J -  3  2  3  Hz),  2  2  3  3  ((CH.3) )CH-)  (s,  3  showed that J_Sn-H 3  the  singlet  2  2  3H, -OMe);  caused  2  =  of  at S 0.32  6  1.00  (t,  29.1  (t,  (s),  168.0  519.1506;  -317 2  J  S  n  (s),  -  C  "  singlet  172.8  8  Hz  >.  (s).  found: 519.1495.  at  doublet  6  (-GeMe ) and 6 2.68  at  2  5  1.00  to a s i n g l e t and irradiation  1 3  2  4  0  -  (-OMe)  caused  Moreover,  2  caused signal enhancement at 5 C nmr (75.6  (q), 2  3.67  ((CH3) CH-).  3  Hz), 13.6 1  8  3  (-GeMe.3) caused signal enhancement at 5 3.67  ((CH ) CH-); 3  2  3  the septet (6 2.68)  i r r a d i a t i o n of the septet at S 2.68 and  2  In a nOe difference experiment,  s i g n a l enhancement at 5 0.32  (-OMe)  2  (septet, IH, ( C H ) C H - ,  3  I r r a d i a t i o n of the  collapse 80 Hz.  2  (-OMe), whereas i r r a d i a t i o n of the  13.1  2  1.43-1.53 (m, 6H, (CH CH CH CH ) Sn-), 2.68  J = 7 Hz), 3.67  of  2  3  (d.  22.5 2  MHz, CDCI3) 6:  (q),  ^Sn-C "  Exact Mass calcd.  4  27.5 4  -  5  H z  (t, >.  3  5  0  J -  S n  8  -  C  3.67  0.6  (q),  - 67 Hz),  <q).  1  4  6  -  4  for C H 0 G e S n (M+'C^): 2 1  4 3  2  - 281 Preparation of methyl  (E)-8-chloro-2-(tri-n-butylstannyl)-3-trimethyl-  germyl- 2-octenoate (283)  and methyl (Z)-8-chloro-3-(tri-n-butylstannvl) -  2-trimethylgermyl-2-octenoate  Following  general  8-chloro-2-octynoate  (284)  procedure  (98)  trimethylgermane (276)  9,  to  a  stirred  (107 mg, 0.569 mmol)  tri-n-butylstannyl-  (0.764 mmol) was added (PPl^^Pd (0.026 mmol) and  the mixture was s t i r r e d at 92-96°C for 5 h. the  and  mixture of methyl  Column  chromatography  black o i l on s i l i c a gel (20 g, e l u t i o n with petroleum ether-diethyl  ether; 17:1) afforded (276) colorless  oils.  and the esters  Subjection  of  (283)  and  (284)  as  mg  (33%) of recovered (276).  Compound (283)  1562, 1207, 830, 594 cm" ; H nmr (400 MHz, 1  -GeMe.3),  (t,  0.90  l  (CH (CH )3)3Sn-,  9H,  3  2  1.34-1.54 tet, 3.54  2  6:  CDC1 ) 3  3  (m,  3  2  2H, C 1 C H ( C H ) - , 2  (75.6 MHz, CDCI3) S:  (t),  27.3 (t, 41.9 (t,  (s,  0.28  9H,  2  2  2  J  3  -  8  Hz),  10H, (CH CH CH CH )3Sn- and two methylenes), 1.79 (quin2  2  2H, methylene, J - 7.5 Hz), 2.18-2.26 (t,  1708,  J « 7 Hz), 0.95-1.00 (m, 6H,  2  2  and 105  exhibited i r (film):  (CH CH CH CH )3Sn-), 1.32 (sextet, 6H, (CH CH CH CH ) Sn-, 3  clear  each of the three o i l s to vacuum (0.1  T o r r , -1 h) afforded 187 mg (55%) of (283), 51 mg (15%) of (284)  (t),  of  3  3  j  J S  S n  n  2  2H, a l l y l i c  J - 7.5 Hz), 3.66 (s,  protons),  3H, -OMe);  1 3  C nmr  0.4 (q), 11.7 (t, ^ s n . c - 328 Hz), 13.6 (q), 27.1  -C C  4  (m,  6  1  H z  >'  2  8  -  9  3j  -Sn-C "  „ 46.8 Hz), 44.7 ( t ) ,  2  0  Hz  51.1 (q),  > •  2  9  -  145.9  8  (*)> (s),  32.5 166.4  - 282 -  (s),  172.9  (s).  Exact  Mass  calcd.  for C H O 2 0  4 0  3 5 2  C4H9):  ClGeSn  539.0960; found: 539.0957. Compound (284) X  H  nmr  (400  exhibited i r (film): 1713, CDCI3)  MHz,  S:  0.31  (s,  1551, 9H,  1197,  829,  -GeMe ),  601 cm" ; 1  0.92  3  (t, 9H,  ( C H ( C H ) ) S n - , J - 7 Hz), 0.94-1.00 (m, 6H, (CH CH CH CH ) Sn-), 3  2  3  3  (sextet,  3  6H,  (CH CH CH CH ) Sn-, 3  2  2  2  J  3  -  8  (CH CH CH CH ) Sn- and two methylenes), 1.77 3  -  2  2  2  3  Hz),  11.6  (t,  29.1  (t,  Hz),  3H, -OMe);  1 3  3.53  (t,  (q),  26.8  (t),  27.5  (t,  J  (t),  32.3  (t),  40.8  (t,  2  S n  -C " (t),  1  8  5  50.9  for C H 0 2 0  -  4 0  3 5 2  Hz), 29.5 (q),  149.2  2  (s),  C l G e S n (M -C H ): +  4  9  160.8  (s),  1.34  3  (m, 1 0 H ,  2H, methylene,  J  2H, C 1 C H ( C H ) - , 2  C nmr (75.6 MHz, CDCI3) 5:  ^ s n . c " 320 Hz), 13.6  44.8  calcd.  (s,  2  1.39-1.54  (quintet,  8 Hz), 2.21-2.27 (m, 2H, a l l y l i c protons),  J - 7.5 Hz), 3.70  2  J  3  172.2  2  J  S  .  n  S  n  (s) .  .  0.1 "  C  2  6  2  -  c  4  (q), Hz), 45.6  Exact Mass  539.0960; found: 539.0949.  Preparation of methvl (E) -7- (tert-butyldimethylsiloxv) -2- ( t r i - n - b u t y l stannvl)-3-trimethvlgermyl-2-heptenoate  (285)  and methyl  (Z)-7-(tert-  butvldimethvlsiloxv)-3-(tri-n-butylstannvl)-3-trimethvlpermyl-2heptenoate  (286)  Bu* Me SIO 2  Following general procedure 9, to a s t i r r e d tert-butyldimethylsiloxy-2-heptynoate  (118)  mixture  (172  mg,  of  methyl  7-  0.637 mmol) and  - 283 tri-n-butylstannyltrimethylgermane (276) (0.76 mmol) was added (PPh ) Pd 3  (0.021  mmol)  and the mixture  was s t i r r e d at 95°C for 14 h .  chromatography of the black o i l  on s i l i c a  gel  (30  g,  4  Column  elution  with  petroleum ether-diethyl ether; 24:1) afforded (276) and the esters (285) and (286) as clear colorless o i l s . to  vacuum  of  Subjection of each of the three o i l s  (0.1 Torr, -1 h) afforded 242 mg (56%) of (285), 58 mg (14%)  (286) and 83 mg (27%) of recovered (276).  ir  (film):  1709,  CDC1 ) 5:  1562,  - 1  X  exhibited  H nmr (400 MHz,  t  2  (CH CH CH CH ) Sn-, 6H,  1100, 836, 775 c m ;  (285)  0.05 (s, 6H, Bu Me SiO-), 0.27 (s, 9H, -GeMe.3), 0.89 ( t , 9H,  3  3  1211,  Compound  2  2  2  J  3  - 7 Hz), 0.90 (s, 9H, Bu Me SiO-) , 0.93-1.01 (m, t  2  (CH CH CH CH )3Sn-), 1.31 (sextet, 6H, (CH CH CH CH ) Sn-, J 3  Hz),  2  2  2  1.35-1.59  (m,  3H, Bu Me SiOCH -, CDCI3) (s),  2  6":  (t,  -5.3 (q), 0.3 (q), 11.7 (t, ^ S n - C "  172.9  (s).  3  J  S n  _  2  2  2  J  S n  .  3  C  1 3  3  -  3  10H), 2.18-2.26 (m, 2H, a l l y l i c protons),  25.9 (q), 26.9 ( t ) , 27.3 ( t ) , 28.9 (t,  42.0  2  J - 7 Hz), 3.65 (s, 3H, -OMe);  t  2  3  7.5  3.61 (t,  C nmr (75.6 MHz,  1 H z  ) •  1  3  -  7  - 19 Hz),  <q) .  1  8  33.2  -  3  (t),  - 46.7 Hz), 51.1 (q), 62.9 ( t ) , 145.5 (s), 166.9 (s),  c  Exact Mass calcd. for C H 0 G e S i S n 25  53  3  (M+^Hg):  621.2007;  found: 621.2011. Compound cm ; -1  L  exhibited  0.06 (s, 6H, B^Me^SiO-), 0.31 (s, 9H,  2  2  2  2  (m,  3.68  J  3  a l l y l i c protons,  (q),  1713, 1557, 1206, 835, 775  t  (CH CH CH CH ) Sn-,  Hz),  (film):  0.90 (s, 9H, Bu Me SiO-), 0.91 (t, 9H, (CH CH CH CH ) Sn-, J -  Hz), 0.93-1.00 3  ir  H nmr (400 MHz, CDCI3) 6:  -GeMe.3), 7  (286)  (s,  3  3  6H,  (CH CH CH CH ) Sn-), 3  2  2  2  2  2  1.33  3  2  3  (sextet,  6H,  - 7.5 Hz), 1.43-1.55 (m, 10H), 2.20-2.28 (m, 2H,  J.s -H "  5  2  n  3H, -OMe);  Hz  >•  1 3  3  -  5  8  2H  > Bu Me SiOCH -,  J  t  2  2  C nmr (75.6 MHz, CDC1 ) 6: 3  -  6.5  -5.2 (q), 0.1  11.6 (t, ^ s n . c - 320 Hz), 13.6 (q), 18.3 ( s ) , 26.0 (q),  26.8  (t,  - 284 -  3  2  iSn-C J  S n  _  Exact  c  ~  6  4  Hz  >>  2  7  -  5  <t. ^Sn-C " 2  1  8  H z  ) . 29.1 <t>. 33.0 ( t ) , 41.1 (t,  - 44 Hz), 50.8 (q), 63.1 ( t ) , 148.9 (s), 161.2  (s),  Mass  621.2007;  calcd.  for  C 5H530 GeSiSn 2  3  (M+^Hg):  172.3  (s) . found:  621.2007.  Preparation of methvl (E)-6-tetrahvdropvranyloxv-2-(tri-n-butvlstannvl)3-trimethvlgermvl-2-hexenoate  (287) and methyl (Z)-6-tetrahvdropyranvl-  oxv-3-(tri-n-butvlstannyl)-2-trimethylgermvl-2-hexenoate  Following general procedure 9, to a s t i r r e d tetrahydropyranyloxy-2-hexynoate n-butylstannyltrimethylgermane  of  the  (276)  black  mixture  of  methyl  (0.382  oil  on  at  mmol) was added (PPl^^Pd 95°C  silica  for  5  h.  Column  gel (15 g, e l u t i o n with  petroleum e t h e r - d i e t h y l ether; 4:1) afforded (276) and the esters and  (288)  as  clear  colorless  oils.  of  (288)  and 86  exhibited i r ( f i l m ) : MHz,  CDC1 ) 3  6:  mg  (287)  Subjection of each of the three  o i l s to vacuum (0.1 Torr, -1 h) afforded 55 mg (50%) (15%)  6-  (119) (39 mg, 0.1725 mmol) and t r i -  (0.009 mmol) and the solution was s t i r r e d chromatography  (288)  of  (287),  (55%) of recovered (276).  1708, 1562, 1212, 1036, 830  17 mg  Compound (287)  cm" ; 1  X  H nmr  (400  0.27 (s, 9H, -GeMe ), 0.90 (t, 9H, ( C H ^ C ^ C ^ C ^ ^ S n - ,  J - 7 Hz), 0.96-1.02 (m,  3  6H,  (C^C^C^CH^Sn-),  1.32  (sextet,  6H,  - 285 (CH CH CH CH ) Sn-, 3  2  2  2  J  3  -  7.5  Hz),  1.44-1.76  2H), 2.25-2.40 (m, 2H, a l l y l i c protons), 3.48-3.55  (m,  IH),  3.65  (s,  3H,  3.39 (dt, IH, J  (q), 3j  (t.  11.7 ( t , ^ S n - C "  -Sn-C 3j  6  -Sn-C "  1  4  H z  7  >.  H z  28.9 (t.  >»  5  1  166.1 (s), 172.8 (s). 577.1561;  1  X  (288)  7  Hz  > •  1  -Sn-C "  - ° (q).  6  1  -  3  2  8  Exact Mass  exhibited  -  2  2  2  J  3  1.34 (sextet, 2.25-2.42  1 3  7 Hz),  0  6 7  >-  3  1  0  9  -  for  -  (*> , 25.4 ( t ) ,  3  <*> •  5  - ° (O.  calcd.  9  8  -  5  3  -  0  •  6  ( >d  1  4  6  3  -  8  <t.  =  s  (M -C H ): +  5  4  Hz),  ir  (film):  1713, 1552, 1200, 1123, 829 9H,  -GeMe.3) -  °-  3  2  2  6H, (CH CH CH CH ) Sn-, J - 7.5 Hz), 1.45-1.93 3  (m,  2H,  ^>  9 1  2  2  allylic  2  (m,  3  protons),  3.36  (dt,  IH,  2  -Sn-C =  3  29.1 (t,  2  0  2  H z  j  >. S  n  1  C  3  -  6  Exact  577.1551.  Mass  9H  >  J  3  14H),  - 9, 6 Hz),  <q)>  1 3  1  (m,  C nmr (75.6 MHz, CDCI3) 6: 0.0 (q), 11.6 9  -  4  ( t ) . 25.5 ( t ) , 27.4 (t,  3  = 20 Hz), 30.4 ( t ) , 30.6 ( t ) , 38.0 (t,  J 2  S  n  j  . S  = 64  C  n  C  Hz), 50.8 (q), 61.9 ( t ) , 66.9 ( t ) , 98.4 (d), 149.5 (s), 160.6 (s), (s).  9  7 Hz), 0.97-1.03 (m, 6H, (CH CH CH CH ) Sn-),  4.59 (t, IH, J - 4 Hz); lj  8  - ° <>>  C H4 04GeSn 23  27.2  3.45-3.54 (m, IH), 3.69 (s, 3H, -OMe), 3.67-3.75 (m, IH), 3.80-3.90 IH),  6:  3  •  Hz  7 Hz),  C nmr (75.6 MHz, CDC1 )  6  H nmr (400 MHz, CDCI3) 6: 0.32 (s,  (CH CH CH CH ) Sn-, 3  2j  2  9,  found: 577.1551.  Compound cm' ;  3  =  -OMe), 3.75 (dt, IH, J = 9 ,  3.83-3.89 (m, IH), 4.61 (t, IH, J - 4 Hz); 0.3  (m, 12H), 1.80-1.90 (m,  c a l c d . for C 3H4504GeSn 2  (M^C^HQ)  : 577.1561;  = 46 172.2 found:  - 286 Preparation of methyl  (E)-4-(3-cvclohexenyl)-2-(tri-n-butvlstannyl)-3-  trimethvlgermvl-2-butenoate  (289)  and methyl  (Z)-4-(3-cyclohexenvl)-3-  (tri-n-butylstannyl)-2-trimethylgermyl-2-butenoate  Following general procedure  mmol)  (0.024  and  the  to  a  stirred  (121) (141  4-(3-cyclohexenyl)-2-butynoate butylstannyltrimethylgermane  9,  (276)  (290)  mg,  mixture  of  methyl  0.792 mmol) and t r i - n -  (1.03 mmol)  was  added  (PPt^^Pd  solution was s t i r r e d at 100°C for 16 h.  chromatography of the black o i l  elution  with  petroleum ether-diethyl ether; 49:1) afforded (276)  and the esters  (289)  and (290)  as clear colorless o i l s .  each  three  oils  vacuum  to  (16%) of (290)  and 113 mg (27%)  Hz),  recovered  1561,  (30  of  g,  of  the  (276).  Compound  (289)  1209, 829, 764 c m ' ; H nmr (400 1  9H, -GeMe.3), 0.89  3  7  gel  Subjection  of  3023, 1708,  MHz, CDC1 ) 6: 0.27 (s, =  silica  (0.1 Torr, -1 h) afforded 246 mg (53%) of (289), 74 mg  exhibited i r ( f i l m ) :  J  on  Column  (t,  9H,  l  (CH^C^CT^C^^Sn-,  0.94-1.01 (m, 6H, (CH2CH3CH2CH2) Sn-), 1.09-1.20 (m, IH), 3  1.31 (sextet, 6H, (CH CH CH2CH )3Sn-, J 3  2  2  -  7  Hz),  1.42-1.53  (m,  6H,  (CH3CH CH CH2)3Sn-), 1.60-1.71 (m, IH), 1.72-1.81 (m, 2H), 1.98-2.09 (m, 2  2  3H), 2.14 (dd, IH, a l l y l i c protons, J - 13, 6 Hz), 3.66 (s, (m, 2H, v i n y l protons);  5.53-5.61 12.2 (t, 28.4  ^sn-C -  (t),  3 2  28.9 (t,  7 Hz), 13.6 ( t ) , 2  J  S  n  .  c  1 3  3H,  -OMe),  C nmr (75.6 MHz, CDCI3) 5: 0.6 (q), 25.5 ( t ) ,  = 19 Hz), 31.9 ( t ) ,  27.2 (t,  3  J  S  n  .  c  - 61 Hz),  33.5 (d), 48.4 (t,  3  J  S n  -  C  - 287 - 4 4 Hz), 51.1 (q), 126.4 (d), 127.1 (d), 147.0 (s), (s).  Exact  Mass  calcd.  for  C  2 2  H  0  4 1  7 2 2  Ge  1 1 8  Sn  166.8  (s),  172.6  (M+^Hg) : 529.1334;  found: 529.1328. Compound (290) exhibited i r (film): 735  3022, 1713,  1551,  1201,  828,  cm" ; H nmr (400 MHz, CDC1 ) 6: 0.32 (s, 9H, -GeMe ), 0.90 (t, 9H, 1  X  3  3  ( C H C H C H C H ) S n - , J - 7 Hz), 0.95-0.98 3  2  2  1.12-1.22  2  (m,  3  (m,  IH),  1.33  (sextet,  6H,  (CH CH CH CH ) Sn-), 3  2  2  2  6H, (CH CH CH CH ) Sn-, J - 7 Hz), 3  2  2  2  3  1.42-1.53 (m, 6H, (CH CH CH CH ) Sn-) , 1.64-1.78 (m, 3H), 1.94-2.07 3  3H),  2  2  2  3  (m,  2.21 (dd, IH, a l l y l i c protons, J - 12, 7 Hz), 2.31 (dd, IH, a l l y l i c  protons, J - 12, 7 Hz), 3.67 (s, 3H, protons); Hz), 2  3  1 3  C nmr  126.6  1  8  H z  >.  3  1  -  2 2  Preparation of  H  4 1  0  5  7 2 2  (t).  3  4  Ge  1 1 8  d  4  S n  7  -  - 65 Hz), 28.4  C  -  160.0  9  2  J-Sn-C =  (s),  4  4  172.3  (t), H z  29.1  (t,  > . 50.8 (q) ,  (s).  Exact  Mass  (291)  Me  stirred  mmol)  J  S n (M+^Hg): 529.1334; found: 529.1332.  3  0.873  3  - ° < >.  Me Ge  a  2H, v i n y l  (E)-(N).(N)-dimethyl-2-tri-n-butylstannvl-3-trimethvl-  germyl-2-butenamide  To  (m,  3  (d), 126.8 (d) , 149.8 (s),  c a l c d . for C  5.63-5.68  (75.6 MHz, CDC1 ) 8: 0.2 (q), 11.8 (t, ^ s n - c =320  13.6 ( t ) , 25.4 ( t ) , 27.5 (t,  ISn-C °  -OMe),  solution  CONMe  2  SnBiig of N,N-dimethyl-2-butynamide (166) (97 mg,  and tri-n.-butylstannyltrimethylgermane  (276)  (353  mg,  0.873 mmol) i n 0.5 mL of dry benzene was added (PPh ) Pd (18.3 mg, 0.016 3  4  - 288 mmol).  The mixture  chromatography  was stirred  at 80°C  for 31 h.  Flash  column  of the black solution on s i l i c a gel (25 g, elution with  petroleum ether-ethyl acetate; 3:2) afforded (276) and the ester (291) as  colorless  oils.  Subjection of each  o i l to vacuum (0.01 Torr, 1  h) afforded 87 mg (19%) of (291) and 253 mg (72%) of recovered The X  colorless  o i l (291) exhibited  (276).  i r (film): 1625, 1578, 826 cm" ; 1  H nmr (400 MHz, CDC1 ) 6: 0.21 (s, 9H, -GeMe ), 3  0.89 (t,  3  9H,  (CH CH CH CH ) Sn-, J - 7.5Hz), 0.98 (t, 6H, (CH CH CH CH ) Sn-, J - 7.5 3  2  Hz), 6H,  2  2  3  3  2  2  2  3  1.33 (sextet, 6H, (CH CH CH CH2) Sn- , J - 7.5 Hz), 3  2  2  1.45-1.56 (m,  3  (CH CH2CH CH2)3Sn-) , 1.92 (s, 3H, vinyl methyl, J_s -H " 4  3  1  2  n  2.90 (s, 3H, -NMe), 2.92 (2, 3H, -NMe). irradiation  In a nOe difference  1 H z  )•  experiment  of the singlet at 5 0.21 (-GeMe.3) caused enhancement of the  singlets at 6 1.92 (vinyl methyl), 6 2.90 (-NMe) and 6 2.92 (NMe). Irradiation  of the singlet  at 6 1.92 (vinyl methyl) caused signal  enhancement at 6 0.21 (-GeMe ) and S 0.98 ((CH CH CH CH2)3Sn-). Finally 3  irradiation  3  2  2  of the singlets at 5 2.90 (-NMe) and 5 2.92 (-NMe) caused  signal enhancement at 6 0.98 ((CH CH2CH CH ) Sn-) and 6 0.21 (GeMe ): 3  1 3  2  2  3  3  nmr (75.6 MHz, CDC1 ) 8: -1.1 (q), 11.0 (t, ^ s n . c - 320 Hz), 26.2  C  3  (q- -Sn-C " 3j  5  34.0  4 Hz  )» 2 7  3  (t.J.Sn-C 3  6  0 Hz  >•  2 9 0  < . ^Sn-C " c  2  2  0 Hz  >•  (q), 38.2 (q), 150.5 (s), 150.7 (s), 173.5 (s). Exact Mass calcd.  for C o H 4 2 2  O N G e S n  (MT^-C^): 504.1509; found: 504.1506.  - 289 -  Preparation of (Z) -1-phenyl-1-tri-n-butvlstannvl-2-trimethylgermylethene (292)  GeMe  Bu Sn 3  3  H  Ph  To a s t i r r e d mixture of phenylacetylene tri-n-butylstannyltrimethylgermane (PPh )4Pd (32 mg, 0.028 mmol). Flash  column  chromatography  s i l i c a gel (15 g, e l u t i o n with colorless  oils.  (276)  of  hexane)  Subjection  of  each  cm* ; 1  Compound X  (292)  exhibited  stirred  the  mmol)  oil  for  resultant  afforded  ir  H nmr (400 MHz, CDCI3) 5: 0.31  1.156  and  (506 mg, 1.24 mmol) was added  afforded 157 mg (27%) of the alkene (292) (276).  mg,  The mixture was  3  120°C.  (118  (276)  to  24  and  (292)  vacuum ( 0 . 1 Torr,  (film): 9H,  2957, -GeMe ), 3  at  black o i l on  and 338 mg (67%) of  (s,  h  as 1 h)  recovered  1597,  824,  0.85  (t,  769 9H,  (CH CH2CH CH2)3Sn-, J - 7.5 Hz), 0.87-0.94 (m, 6H, (CH3CH2CH2CH2)3Sn - ) , 3  1.26  2  (sextet, 6H, (CH3CH2CH2CH2)3Sn-, J - 7.5  (CH CH2CH CH )3Sn-), 3  2  2  6.78  (s,  IH,  6.96-7.01 (m, 2H, aromatic protons), 7.5,  1.5 Hz), 7.27  6: 0.0 (q), Hz),  11.7 (t,  29.0 (t,  52 Hz),  151.3  2  J  S n  -\l _c S n  1  9  H z  164.2  >.  3  2  5  -  3  J_Sn-H  (m,  6H,  = 161 Hz),  7.12 (td, IH, aromatic proton, J 1 3  2 0 Hz), 13.6 (q), 1  1.35-1.45  proton,  (m, 2H, aromatic protons);  -C -  (s),  vinyl  Hz),  4  (s).  (M+-CH3): 512.1521; found: 512.1518.  < >. d  Exact  1  2  7  •  9  Mass  =  C nmr (75.6 MHz, CDCI3) 27.3 (t,  < >. d  1  4  9  calcd.  •  3  5  J  <d  for  S  n  . 2j  C  -  6  2  -Sn-C -  C 3H GeSn 2  42  - 290 General Procedure 10:  Transmetalation of ethvl ( E ) - 2 - ( t r i - n - b u t y l -  stannvl)-3-trimethylgermvl-2-butenoate intermediate with  To  a  cold  electrophiles  .(-98°C),  stirred  solution of the appropriate ester (1  equiv) i n dry THF (-20 mL per mmol) was equiv)  as  a  solution  in  hexane.  s t i r r e d at -98°C for 15-20 min. equiv),  which  and reaction of the resultant  had  been  n-butyllithium  appropriate  electrophile  min unless stated otherwise.  warm  to room temperature.  up  to  Saturated aqueous ammonium chloride (2  mL/mmol) and ether (20 mL/mmol) were added and the mixture to  (10-20  d i s t i l l e d or had been passed through  basic alumina was added, and the mixture was s t i r e d at -98°C for 45  (1.1-1.2  The r e s u l t i n g yellow solution was  The  freshly  added  was  allowed  The organic layer was washed three times  with saturated aqueous ammonium chloride, dried over anhydrous magnesium sulfate,  and concentrated.  Column chromatography of the residual o i l on  s i l i c a gel (elution with petroleum ether-diethyl ether) and d i s t i l l a t i o n of the o i l thus obtained afforded pure product.  Preparation of ethyl  (Z)-2-(2-pronenvl)-3-trimethylgermyl-2-butenoate  (294)  Following  general procedure 10, to a cold ( - 9 8 ° C ) ,  of the ester (279)  s t i r r e d solution  (517 mg, 0.994 mmol) i n 20 mL of dry THF was added  a  - 291 -  s o l u t i o n of n-butyllithium (1.19 mmol) i n hexane.  After the mixture had  been s t i r r e d at -98°C for 15 min, 3-iodopropene (-15 mmol) was added and the  solution  was s t i r r e d at -98°C for 40 min.  Normal workup, followed  by f l a s h column chromatography of the residual o i l on s i l i c a gel (25 elution  with  petroleum  ether-diethyl  ether;  24:1)  and d i s t i l l a t i o n  ( a i r - b a t h temperature 1 3 5 ° C / 1 0 Torr) of the o i l thus obtained, 216  mg  (80%)  of  the  ( f i l m ) : 3081, 1713, CDC1 )  6:  3  (s, (q,  0.27  (s,  ester  1639,  (294).  1273,  1201,  9H, -GeMe ), 1.27 3  3H, v i n y l methyl), 3.16 3  IH, H , J - 17, 2 Hz), 5.78 A  difference  experiment,  This colorless o i l exhibited i r 1045, (t,  (M+-CH ): 3  and  S  0.27  257.0596;  832 cm* ; E nmr 1  l  (270 MHz,  3H, -OCH CH , J - 7 Hz), 2  (dt,  IH, H , J - 17, 10, 6 Hz). c  irradiation  of  the  (-GeMe ). 3  Exact  singlet  (HQ), Mass  S  In  3.16  calcd.  nOe  (vinyl  (bis-allylic C^^H 90 Ge  for  2  2  found: 257.0593.  Following general procedure 10, to a cold ( - 9 8 ° C ) , the ester (279)  (dd,  a  at 5 1.90  Preparation of ethyl (Z)-2-methvl-3-trimethylgermvl-2-butenoate  of  1.90  3  (dd, IH, Hg, J - 10, 2 Hz), 4.98  methyl) caused signal enhancement at 5 5.78 protons)  afforded  (d, 2H, b i s - a l l y l i c protons, J - 6 Hz), 4.15  2H, -OCH CH , J - 7 Hz), 4.96 2  g,  stirred  (295)  solution  (179 mg, 0.344 mmol) i n 10 mL of dry THF was added a  s o l u t i o n of n-butyllithium (0.378 mmol) i n hexane.  After  the  mixture  - 292 had been s t i r r e d at -98 C for 20 min, iodomethane (7 mmol) was added and D  the s o l u t i o n was s t i r r e d at -98°C for 45 min. by  workup,  followed  f l a s h column chromatography of the residual o i l on s i l i c a gel (10 g,  e l u t i o n with (air-bath  petroleum  temperature  ether-diethyl 130°C  /0.1  ether;  Torr)  afforded 65 mg (77%) of the ester (295). ir  Normal  ( f i l m ) : 1713, 1595,  0.26  (s,  vinyl Hz).  Exact  1.92  Mass  of  the  and oil  distillation  thus obtained,  This colorless  oil  exhibited  1270, 1073, 831 cm* ; H nmr (270 MHz, CDC1 ) 6: 1  l  3  9H, -GeMe.3), 1.29  methyl),  17:1)  (s,  (t,  3H, -OCH CH , J - 7 2  3H, v i n y l methyl), 4.16  calcd.  for  CoH 0 Ge 17  2  Hz),  3  1.89  (s,  3H,  (q, 2H, OCH CH , J - 7  (M+-CH3):  2  231.0440;  3  found:  231.0438.  Preparation of ethvl butenoate  (Z)-2-(3-methvl-2-butenvl)-3-trimethvlgermvl-2-  (296)  Following  general procedure 10, to a cold ( - 9 8 ° C ) ,  of the ester (279) solution  of  (108 mg, 0.207 mmol) i n 10 mL of dry THF was added  n-butyllithium  had been s t i r r e d at -98°C mmol)  was  added  s t i r r e d solution  and  the  (0.249 mmol) i n hexane.  for  20  min,  solution  was  After the mixture  4-bromo-2-methyl-2-butene  on  silica  gel  (-5  s t i r r e d at -98°C for 45 min.  Normal workup, followed by flash column chromatography of oil  a  the  residual  (10 g, e l u t i o n with petroleum ether-diethyl ether;  - 293 17:1)  and d i s t i l l a t i o n (air-bath  residual  oil  thus  temperature  1  X  H  nmr. (270  3  (br s,  methyl),  bis-allylic  3  3.09  (d,  2H,  -0CH CH , J - 7 Hz), 4.99 2  1712,  MHz, CDC1 ) 6: 0.25  -0CH CH , J - 7 Hz), 1.66 2  Torr)  of  the  obtained, afforded 46 mg (74%) of the alkene (296).  This c o l o r l e s s o i l exhibited i r (film): cm' ;  110°C/0.1  3  (br t,  (s,  1590,  1273,  1178,  9H, -GeMe ) , 1.27  protons,  (t, 3H,  3  6H, v i n y l methyls),  1.90  (s,  3H,  J - 7 Hz), 4.15  IH, v i n y l proton, J  =  7  831  vinyl (q, 2H,  Hz).  Exact  Mass c a l c d . for C H 0 G e (M+-CH ): 285.0910; found: 285.0911. 1 3  2 3  Preparation of ethvl butenoate  2  3  (Z)-2-(3-chloropropvl)-3-trimethvlgermyl-2-  (297)  Cl Following  general procedure 10, to a cold ( - 9 8 ° C ) ,  of the ester (279) solution  of  s t i r r e d solution  (125 mg, 0.240 mmol) i n 10 mL of dry THF was added  n-butyllithium  (0.288 mmol) i n hexane.  After the mixture  had been s t i r r e d at -98°C for 20 min, 3-chloro-l-iodopropane was for  a  (-5  mmol)  added and the solution was s t i r r e d at -98°C for 45 min and of -78°C 1 h.  residual  Normal oil  ether: 17:1)  workup,  followed  by  column  chromatography  of  the  on s i l i c a gel (10 g, e l u t i o n with petroleum ether-diethyl and d i s t i l l a t i o n (air-bath temperature 1 0 0 ° C / 0 . 1  Torr)  the o i l thus obtained, afforded 31 mg (42%) of the chloride (297). c o l o r l e s s o i l exhibited i r (film): 1712,  1591, 1275,  1135,  of This  831 c m ' ; 1  X  H  - 294 -  nmr  (270 MHz,  7 Hz),  1.86  methyl),  (quintet,  2.53  (t,  C 1 C H C H C H - , J. 2  calcd.  2  5: 0.28  C D C I 3 )  for C H n  2 0  O  2  2H,  3 5 2  -GeMe ),  2  2  2  4.16  2  J  2  (q,  (M^CH^:  1.28  3  C1CH CH CH -,  ClGe  Preparation of ethvl butenoate  9H,  2H, C 1 C H C H C H - , J -  7.5 H z ) ,  2  (s,  2H,  (t,  7.5 H z ) , -  7.5  2  1.94 Hz),  -OCH CH , J 2  3H, 0 C H C H , J (s,  3H,  3.52  7 Hz).  3  3  -  vinyl  (t,  2H,  E x a c t Mass  293.0364; f o u n d : 293.0355.  2-methvl-3-(tri-n-butvlstannyl-2-trimethylgermyl-3-  (299)  SnBu  3  Me Ge  Me  3  To  a  cold  (-98°C),  stirred  s o l u t i o n of  stannyl-2-trimethylgermyl-2-butenoate mL  of  dry  hexane.  THF  After  45 min and a t example) s i l i c a gel  been  stirred  at  for  15  mmol) was added and the mixture was s t i r r e d at  - 7 8 ° C f o r 45 min.  Normal  workup  (as  10  (0.318 mmol)  -98°C  in  (10 g , e l u t i o n w i t h petroleum e t h e r - d i e t h y l (air-bath  temperature  a f f o r d e d 105 mg (75%)  exhibited  ir  CDC1 ) 6:  0.20  3  had  in  min,  -98°C  the  in  for  previous  f o l l o w e d by f l a s h column chromatography o f the r e s i d u a l o i l on  distillation obtained,  (138 mg, 0.265 mmol)  was added a s o l u t i o n o f n - b u t y l l i t h i u m  the mixture  iodomethane (-5  (280)  ethyl-(Z)-3-tri-n-butyl-  (film): (s,  9H,  1689,  120°C/0.05  o f the e s t e r  1577,  1252,  1108,  - G e M e ) , 0 . 8 2 - 0 . 9 3 (m, 3  ether;  Torr)  (299).  and  o f the o i l  thus  This colorless  oil  824 c m " ; U 1  6H,  17:1)  l  nmr (400 MHz,  (CH CH CH CH ) Sn-), 3  2  2  2  3  - 295 -  0.89  (t,  Hz),  1.31  Me),  9H, (CH (CH )3)3Sn-, J - 7.5 Hz), 1.26 3  3  -OCH H CH' , J lH -H c  D  D  3  -  3H, -OCH CH , J - 7 2  (sextet, 6H, (CH CH CH CH ) Sn-, J - 7 . 5  1.39-1.50 c  (t,  2  1  1  H  z  H  (m, . C D  2  2  3  2  J  H  D  2  (d, IH, H , J  c a l c d . for C  2 1  (d, IH, H , J H  4 3  0  7 4 2  Ge  1 1 8  S n  -H "  (dq, IH,  S n  _  - 68 Hz, i H ^ H g "  H  1  4  6  H z  1  5  H z  Preparation of (Z)-2-(2-propenyl)-3-trimethvlgermyl-2-buten-l-ol  To  a  cold  (-78°C),  stirred  solution of the ester (294)  (304)  (383 mg,  1.418 mmol) i n 15 mL of dry d i e t h y l ether was added 3.12 mL (3.12 of  a  IM s o l u t i o n of DIBAL i n hexane.  at -78°C for 1 h and chloride  (-1  temperature.  3H,  • ^H -H " > « Exact Mass A. fi S n ( M ^ C ^ ) : 519.1491; found: 519.1492. 3  B  (s,  (dq, IH, -OCHcHrjCH^,  3  A  1.41  Hz), 4.06  3  H  . J-H -H' - 7 Hz), 5.27  5.66  2  . . - 7 Hz), 4.17  D  1.5 Hz),  Hz),  3  6H, (CH CH CH CH ) Sn-, J - 7 . 5 - 11 Hz,  H  2  3  at  0°C  for  2  mmol)  The reaction mixture was s t i r r e d h.  Saturated  aqueous  ammonium  mL) was added and the mixture was allowed to warm to room The r e s u l t i n g white  slurry  was  treated  with  anhydrous  magnesium sulfate and the mixture was f i l t e r e d through a short column of Florisil the  (5 g, e l u t i o n with d i e t h y l ether).  combined  eluate,  followed  by  Removal of the solvent from  d i s t i l l a t i o n (air-bath temperature  1 1 0 ° C / 1 0 Torr) of the residual material afforded 327 mg alcohol (304). 1638,  1237,  (100%)  of  the  This colorless o i l exhibited i r (film): 3336 (br), 3079,  993, 829 cm" ; H nmr (400 1  X  MHz,  CDCI3)  S:  0.30  (s,  9H,  - 296 -  -GeMe ),  1.51-1.60 (broad s,  IH, -OH), 1.79  (s,  3H, v i n y l methyl),  3.03  2H, b i s - a l l y l i c protons, J - 7 Hz), 4.09  (s,  2H, -CH OH), 5.01  (dd,  (dd, IH, H , J - 18, 1.5 Hz), 5.84  (ddt,  3  (d, IH,  H ,  J -= 10, 1.5 Hz), 5.04  B  IH, H , 1 - 18, 10, 7 Hz). c  2  A  Exact Mass  calcd.  for  C H 0Ge 9  (M+-CH;}):  17  215.0491; found: 215.0495.  Preparation of butene  (Z)-l-methoxymethoxy-2-(2-propenvl)-3-trimethvlgermvl-2-  (305)  \  To  a  cold  (0°C),  stirred  solution of the alcohol (304)  (101 mg,  0.439 mmol) i n 6 mL of dry dichloromethane was added 66 /iL (0.878 of  chloromethylmethyl ether and 81 nh (0.878 mmol) of e t h y l d i i s o p r o p y l -  amine.  The reaction mixture was s t i r r e d at 0°C for  temperature  for  23  h.  with  saturated  sium  sulfate  70-75°C/0.1 (305).  1  h  at  The organic layer was washed three  room (5  times  aqueous sodium bicarbonate, dried over anhydrous magneand  concentrated.  Distillation  (air-bath  temperature  Torr) of the residual o i l afforded 79 mg (66%) of the ether  This colorless o i l exhibited i r (film): 3079, 1638,  cm" ; H nmr (400 MHz, CDC1 ) 6: 0.29 1  and  The solvent was removed and petroleum ether  mL) was added to the residue.  760  mmol)  X  v i n y l methyl), 3.00  3  (s,  1039,  9H, -GeMe ), 1.81 3  995,  (s, 3H,  (d, 2H, b i s - a l l y l i c protons, J = 7 Hz), 3.40 (s, 3H,  - 297 -CH OCH OCH ),  4.01  5.00  (dd, IH, H , J - 18, 1.5 Hz), 5.02 A  5.79  (ddt, IH, H , J - 18, 10, 7 Hz).  2  2  3  (s,  2H, -CH OCH OCH ), 4.63 2  2  2H, -CH OCH OCH ), 2  (dd, IH, H , J -  10,  B  2  3  1.5  Hz),  Exact Mass c a l c d . for C H 0 G e  c  (M+-CH ):  (s,  3  1 1  2 1  2  259.0754; found: 259.0752.  3  Preparation of (Z)-3-iodo-l-methoxymethoxv-2-(2-propenvl)-2-butene  (306)  o  To a s t i r r e d solution of the ether (305)  (55.8 mg, 0.2036  mmol)  in  5 mL of dry dichloromethane was added s o l i d iodine (52 mg, 0.2036 mmol). The mixture was s t i r r e d at room temperature u n t i l a persisted  and  was  of  followed  by  ether).  Concentration  oil  exhibited i r (film): 3079, 1639,  nmr (400 MHz, CDC1 ) 5: 2.57 3  allylic  protons,  -CH OCH OCH ), 4.65 2  Hz),  2  5.05  1.5 Hz). 2.57 (H ). c  3  J  of  the  -  (s,  combined  1039,  (306).  995,  3H, v i n y l methyl), 3.07  7 Hz), 3.42  (s,  iodide  (s,  2  2H, -CH 0CH. 0CH ) , 5.04 2  2  3  (dd, IH, H , J - 11, 1.5 Hz), 5.75 B  2  This  829 c m ; H - 1  (d,  2H,  3H, -CH 0CH 0CH ), 4.20 3  X  bis-  (s, 2H,  (dd, IH, H , J - 15,  1.5  (ddt, IH, H , J - 15,  11,  A  c  In a nOe difference experiment i r r a d i a t i o n of the s i n g l e t at 6  ( v i n y l methyl) caused signal enhancement at 6 5.05 Exact  236.9780.  color  d i s t i l l a t i o n (air-bath temperature 6 5 ° C / 0 . 1 Torr)  the residual o i l afforded 47.6 mg (83%) of the  colorless  purple  then passed through a short column of basic alumina  (2 g, e l u t i o n with petroleum eluate,  pale  Mass  calcd.  for  C H OI 7  10  (M+'C^O):  (H ) and 6 5.75 B  236.9778;  found:  - 298 Preparation of (Z)-3-iodo-2-(2-propenvl)-2-buten-l-ol  To a s t i r r e d solution of the alcohol (304)  (274 mg, 1.19 mmol) i n 10  mL of dry dichloromethane was added s o l i d iodine (303 The  mixture  was  (307)  mg,  1.19  mmol).  s t i r r e d at room temperature u n t i l a pale purple color  persisted.  Concentration of the solution,  graphy  the r e s i d u a l o i l on s i l i c a gel (10 g, e l u t i o n with petroleum  of  ether d i e t h y l ether; 7:3)  followed by column  temperature  50°C/  0.05 Torr) of the o i l thus obtained, afforded 203 mg (72%) of the  iodide  (307).  This c o l o r l e s s o i l exhibited i r (film):  1057, Hz), Hz), 5.05  and d i s t i l l a t i o n (air-bath  chromato-  916, 2.58 4.25  759 c m ' ; 1  (s,  X  H nmr (80 MHz, CDC1 ) 5: 1.58 3  3H, v i n y l methyl), (d,  3371 (br),  3.05  2H, -CH 0H, J - 7 2  B  1638,  IH, -OH, J - 7  (d, 2H, b i s - a l l y l i c protons, J = 6  Hz), 5.03  (dd, IH, H , J — 10, 2 Hz), 5.78  (t,  3080,  (dd, IH, H , J - 16, 2 Hz), A  (ddt, IH, H , J - 16, 10, c  6  Hz).  Exact Mass c a l c d . for C H 0 I (M+) : 237.9857; found: 237.9857. 7  n  Preparation of (Z)-l-bromo-3-iodo-2-(2-propenvl)-2-butene  To  a  cold  (-20°C),  (308)  s t i r r e d solution of triphenylphosphine  (53 mg,  - 2 9 9 -  0 2 .0 2  m m ) o l i n 3 m L o f d r y d c i h o l r o m e t h a n e w a s a d d e d 1 1 x / L  o f b r o m n i e p r o d u c n ig a p a e l  y e o lw  s o l u t i o n .  T r p ih e n y p lh o s p h n ie  w  a d d e d i n v e r y s m a l a m o u n s t u n t i l t h e s o l u t i o n t u r n e d c l e a r . A o f t h e a l c o h o l ( 3 0 7 ) d r o p w s i e  o v e r  a  ( 5 3 m g ; 0 2 .0 2 m m ) o l i n 2 m L o f d r y  p e r o id  o f 5 m n i. A f t e r t h e d r o p p n ig f u n n e l h  r i n s e d w t i h 0 5 . m L o f C H C 1t h e r e a c t i o n m x i t u r e w a s a o l l w e d 2  r o o m  t e m p e r a t u r e .  2  T h e s o l u t i o n w a s c o n c e n t r a t e d a n d p e t r o e l u m e t h  m L ) w a s a d d e d t o t h e r e s i d u e .T h e r e s u l t a n t s l u r r y w a s p a s s e d s h o r tc o u l m n  o f F l o r i s i l ( 2 g , e l u t i o n w t i h p e t r o e l u m e t h e r ) .  t r a t i o n o f t h e e l u a t e f o o lw e d 6 0 ° C / 0 5 . T o r r )o f t h e  b y  d i s t i l l a t i o n ( a i r b a t h  t e m p e r a t u r  r e s i d u a lo i l a f f o r d e d 5 6 m g 9 ( 2 % ) o f t h e  b r o m d i e ( 3 0 8 ) .T h s i c o l o r l e s s o i l e x h i b i t e di r ( f i l m ) : 3 0 8 0 , 1 2 0 5 ,9 1 9 3 1 .0 ( d ,  c m " ; H n m r ( 8 0 M H z , C D C ) 1 6: 2 5 .8 ( s , 11  3  2 H , b i s a l l y l i c p r o t o n s , J -  ( d d , I H , H , J A  2 H , C H  1 6 , 2 H z ) , 5 0 .8 ( d d , I H , H , J = 1 0 , 2 H B  c  XI:  1 6 4 0 ,  3 H , v i n y l  6 H z ) , 4 2 .0 ( s ,  I H , H , J = 1 6 , 1 0 , 6 H z ) . E x a c t 3 0 1 8 .9 9 3 ; f o u n d :  C  M a s  c a l c d . f o r C H B r I 1 8  7  0 1  3 0 1 8 .9 9 2 .  S y n t h e s s i o f t r i c y c l i c a n d b i c y c l i c r i n g s y s t e m s  G e n e r a lP r o c e d u r e  1 1 :  P d ( 0 ) c a t a y lz e d  n it r a m o e l c u a lr c y c l i z a t i o n o f  v i n y l s t a n n a n e v i n v l i o d i d e s .  T o s t i r r e d d r y a c e t o n i t r i l e ( 2 m L ) i n a t h r e e n e c k e d f l a s k w a s  r o u n d b -  a d d e d t r p ih e n y p lh o s p h n ie ( 0 0 .6 e q u i v ) , p a l a d i u m ( l ) a c e t a t  - 300 (0.03 equiv) and reaction  triethylamine  mixture  equiv),  in  that  order,  and  the  was heated to 4 5 - 5 0 ° C for 20-30 min u n t i l a clear red  solution persisted. 10  (2  The red solution was transferred (via syringe) to a  mL round-bottomed  flask  equipped  with  a  condenser containing a  s o l u t i o n of the appropriate vinylstannane-vinyl iodide (1 equiv) i n -0.5 mL  of  dry  acetonitrile.  The resultant mixture was s t i r r e d at 65-85°C  u n t i l t i c analysis of an aliquot indicated complete consumption starting  material.  Concentration  of the solution,  of  the  followed by column  chromatography of the residual o i l on s i l i c a gel (elution with petroleum e t h e r - d i e t h y l ether) and d i s t i l l a t i o n of the o i l thus obtained, afforded the appropriate diene.  Preparation of compound (313)  To a cold ( - 2 0 ° C ) , equiv)  in  5  mL of  s t i r r e d solution of lithium diisopropylamide dry THF was added the ester (206)  (122 mg, 0.4018  mmol) as a s o l u t i o n i n 5 mL of dry THF and the solution was -20°C  for  30 min.  mg,  stirred  at  HMPA (3 equiv) was added to the yellow s o l u t i o n and  the mixture was s t i r r e d at -20°C for 15 min. (127  (2.0  The  iodo  bromide  0.4219 mmol) was added as a solution i n 2 mL of dry THF.  (308) The  - 301 solution  was  stirred  at  ammonium chloride (-1 mL) allowed three  to  warm  times  -20°C was  for 30 min and then saturated aqueous  added  and  to room temperature.  with  saturated  aqueous  the  ether-diethyl  ether;  17:1)  and  mixture  was  The organic solution was washed ammonium c h l o r i d e ,  anhydrous magnesium sulfate and concentrated. phy of the r e s i d u a l o i l on s i l i c a gel  resultant  (15  dried  over  Flash column chromatogra-  g,  elution  distillation  with  (air-bath  petroleum temperature  1 5 5 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 145 mg (69%) of ester 1212, 54  (313).  This colorless o i l exhibited i r ( f i l m ) : 3030, 1733,  769 c m ; U nmr (400 MHz, CDC1 ) 6: 0.15 - 1  3  Hz),  1.60-1.79  methyl), 2.58 3.00  (d,  3  J  S n  5.73  (m,  3H),  2.01-2.16  (m,  (d, IH, H , J - 14 Hz), 2.65  1638,  9H, -SnMe.3, ^Sn-H ~  3H),  2  2.55 (s,  (dd, IH, H , J - 16,  E  D  3H, v i n y l 6  Hz),  IH, Hg, J - 14 Hz), 3.05 (dd, IH, H , I - 16, 6 Hz), 3.69 D  3H, -OMe), 4.96 Hz),  (s,  l  the  (dd, IH, H , J - 17, 2 Hz), 5.03 B  (ddt, IH, H , J - 17, 10, 6 Hz), 5.99 c  - H - 74 Hz).  (dd, IH, Hg, J - 10, (t,  2 6  2  2  IH, Hp, J - 3.5 Hz,  Exact Mass calcd. for C H 0 I S n (M+-CH3): 1 7  (s,  509.0001;  found: 508.9992.  Preparation of  l-carbomethoxv-7-methyl-8-(2-propenyl)bicyclof4.3.01-  nona-5.7-diehe  (314)  - 302 -  Following  general  procedure  vinylstannane-vinyl iodide (313) acetonitrile  was  added  a  2  11,  to  a  stirred  solution  (48 mg, 0.092 mmol) i n 0.5 mL a c e t o n i t r i l e  solution  of the  mL of of  dry  in  situ  generated palladium(O), and the reaction mixture was s t i r r e d at 80°C for 4  h.  Tic  nent.  analysis of an aliquot indicated the presence of one compo-  Concentration,  pipette)  followed  by  column  chromatography  (Pasteur  of the r e s i d u a l o i l on s i l i c a gel (2 g, e l u t i o n with petroleum  ether-diethyl 55°C/0.05  ether;  Torr)  of  9:1)  and  distillation  (air-bath  temperature  the o i l thus obtained, afforded 17 mg (81%) of the  triene  (314).  1160,  913 cm" ; H nmr (400 MHz, CDC1 ) 6: 1.43-1.52 (m, IH), 2.33-2.42 1  2H,  exhibited  ir  (film):  1723,  1637,  l  (d, IH, H , J - 16 Hz), 2.68 E  H , J - 6.5 Hz), 3.65 D  1.5 Hz), 4.99 5.72  oil  3  (m, IH), 2.39 (d,  This colorless  (ddt,  (s,  (d, IH, H , J - 16 Hz),  3H, -OMe), 4.98  (dq, IH, H , J - 17, 1.5 Hz), 5.47 A  2.88  E  (t,  (dq, IH, Hg, J = 10, IH, Hp, J - 4  Hz),  IH, H , J - 17, 10, 6.5 Hz). Exact Mass c a l c d . for C H o 0 2 c  15  2  (M+): 232.1464; found: 232.1464.  To a cold ( - 2 0 ° C ) ,  s t i r r e d solution of lithium diisopropylamide  (2.0  - 303 equiv)  i n 3 mL of dry THF was added the ester (207)  (47 mg, 0.375 mmol)  as a s o l u t i o n i n 3 mL of dry THF and the solution was s t i r r e d for  15  min.  HMPA  in  -20°C  (3 equiv) was added to the yellow solution and the  mixture was s t i r r e d for 15 min at - 2 0 ° C . (308),  at  2 mL of dry THF was added.  A solution of the bromo iodide The solution was s t i r r e d for 1 h  at -20°C and then saturated aqueous ammonium chloride (-1 mL) was and  added  the resultant mixture was allowed to warm to room temperature.  organic s o l u t i o n was washed three times with saturated aqueous chloride,  dried  over  anhydrous  magnesium  sulfate  Flash column chromatography of the residual o i l on e l u t i o n with petroleum ether-diethyl ether; 17:1)  ammonium  and concentrated.  silica  gel  3050, 1705,  1638,  This colorless o i l exhibited i r  770 c m ' ; 1  X  (film):  H nmr (400 MHz, CDC1 ) 6:  1.95  (ddd, IH, J - 15, 10, 4 Hz), 2.02-2.15 (m, 2H), 2.26-2.37 (m, (s,  2  S n  - H - 52 Hz), 1.51-1.60 (m, 2H), 1.74-1.85 (m, 2H),  3H, v i n y l methyl), 2.70  IH, H , J - 14 Hz), 3.03 E  6.5 Hz), 3.69  (s,  5.02  (ddt, IH, Hg, J - 10, 1.5,  (dd, IH, H ,  3H, -OMe), 4.95  D  (ddt, IH, H , J = 17, 1.5, A  1 Hz), 5.63  (ddt, IH, H , J c  5.5 Hz, J 3  S n  -H "  8  3  H z  )-  c a l c d . for C H 8 0 2 l S n (M+-CH3): 523.0158; found: 523.0167. 2  (d,  D  E  (dd, IH, Hp, J - 7.5, 18  IH),  (dd, IH, H , J - 16, 6.5 Hz), 2.73  (d, IH, H , J - 14 Hz). 3.07  16,  6.5 Hz), 6.00  0.13  3  9H,  3  J  1210,  g,  afforded  (s,  2.56  -SnMe ,  1430,  (10  and d i s t i l l a t i o n ( a i r -  bath temperature 1 6 0 - 1 6 5 ° C / 0 . 0 1 Torr) of the o i l thus obtained, 40 mg (51%) of the ester (315).  The  -  I  -  1 Hz),  17,  10,  Exact Mass  - 304 Preparation of l-carbomethoxv-8-methvl-9- (2-propenvl)bicvclo f 5 . 3 .01 deca-6.8-diene  (316)  Following general vinylstannane-vinyl acetonitrile generated for  was  procedure iodide  added  a  11,  (315) 2  to  a  stirred  solution  of  the  (36 mg, 0.061 mmol) i n 0.5 mL of dry  mL a c e t o n i t r i l e  solution  of  in  situ  palladium(O), and the reaction mixture was s t i r r e d at 70-75°C  2.5 h.  T i c analysis of an aliquot indicated  component.  Concentration,  followed  the  presence  ether;  9:1)  and  one  by column chromatography (Pasteur  pipette) of the residual o i l on s i l i c a gel (2 g, e l u t i o n with ether-diethyl  of  distillation  (air-bath  petroleum temperature  5 5 - 6 0 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 14 mg (85%) of the triene  (316).  This colorless o i l exhibited i r (film): 1723,  1170 cm" ; H nmr (400 MHz, CDC1 ) 6: 1.32 1  X  3  (qt,  1638,  1440,  IH, J - 12, 3 Hz),  1.40  (td, IH, J = 13, 2.5 Hz), 1.59-1.79 (m, 2H), 1.66 1.85-1.95 (m, IH), 2.05-2.26 (m, 3H), 2.40 (d,  IH,  Hg,  J  —  (dd,  3H, v i n y l methyl),  (d, IH, H , J - 16 Hz), E  16 Hz), 2.80-2.95 (m, 2H), 3.71 (s,  (ddt, IH, Hg, J - 10, 2, 1 Hz), 5.00 5.68  (s,  IH, Hp, J - 9.5 Hz), 5.73  (ddt, IH, H , J A  3H, -OMe), 17,  2,  2  4.98 Hz),  (ddt, l H , H , J - 17, 10, 6.5 Hz). c  Exact Mass c a l c d . for C H 2 0 2 (M+) : 246.1619; found: 246.1621. 16  1  2.73  - 305 Preparation of compound (317)  To a cold ( - 2 0 ° C ) , equiv)  in  s t i r r e d solution of lithium diisopropylamide  3 mL of dry THF was added the ester (205)  (58 mg, 0.20 mmol)  as a s o l u t i o n i n 3 mL of dry THF and the solution was s t i r r e d for  30  min.  HMPA  mmol)  was  for  -20°C  1  h  and  then  saturated  (69 mg,  The solution  aqueous  ammonium  (1 mL) was added and the resultant mixture was allowed to warm  to room temperature. saturated  aqueous  The organic layer ammonium  sulfate and concentrated. yellow  The iodo bromide (308)  added as a solution i n 2 mL of dry THF.  was s t i r r e d at -20°C chloride  at  (3 equiv) was added to the yellow solution and the  mixture was s t i r r e d at -20°C for 15 min. 0.229  (2.1  oil  on  silica  was  chloride,  washed  dried  three  times  with  over anhydrous magnesium  Flash column chromatography of  the  residual  gel (10 g, e l u t i o n with petroleum ether-diethyl  ether; 97:3)  followed by d i s t i l l a t i o n (air-bath  0.05  of the o i l thus obtained, afforded 67 mg (66%) of the ester  Torr)  (317).  cm" ;  Hz),  2.0 (ddd, IH, H  6.5  Hz),  1  X  H nmr (400 MHz, CDCl ) 6: 0.17 3  2.44-2.61  H  (s,  2  S n  _ H " 54 8,  (m, 2H, H ) , 2.50 (d, IH, H , J - 14 Hz), 2.55  (s,  H  G  E  D  J - 15.5,  9H, -SnMe.3, J  1230,  , J - 13, 8, 4 Hz), 2.29 (ddd, IH, H , J - 13,  3H, v i n y l methyl), 2.67 (dd, IH, H , 1 - 15.5, D  140-145°C/  This colorless o i l exhibited i r (film): 3080, 1720, 1639,  771  H ,  temperature  6.5 Hz),  6.5 Hz), 3.04 (d, IH, H , J_ - 14 Hz), 3.68 E  3.02 (s,  (dd,  IH,  3H, -OMe) ,  - 306 4.97  (ddt, IH, H , J - 17.5, A  2.5,  1.5  Hz), 5.63  2.5,  1.5 Hz), 5.02  (ddt, IH, H , J_ c  H , J - 2.5 Hz, J_Sn-H " 3  3  8  Hz  F  >-  17.5,  (ddt, IH, H , B  10.5,  J  6.5 Hz), 5.98  10,  (t, IH,  I r r a d i a t i o n of the t r i p l e t at  s i m p l i f i e d the multiplet at S 2.44-2.61.  -  6  5.98  I r r a d i a t i o n of the signal at S  5.63 s i m p l i f i e d the signal at 6 2.67. to a doublet (J - 15.5 Hz) and signal  at  S 3.02 to a doublet (J - 15.5 Hz).  the  Moreover, i r r a d i a t i o n of  the signal at S 5.63 s i m p l i f i e d the signals at S 4.97 and 6 5.02 to a dt (J  -  2.5,  1.5  Hz).  Exact  Mass  calcd.  for  C H 4 0 I S n (M+-CH3): 16  2  2  494.9845; found: 494.9838.  Preparation of 1-carbomethoxy-4-methyl - 3- (2 - propenvDbicyclo f 3. 3 . 01 octa-3.5-diene  (318)  Following general procedure 11, to a s t i r r e d solution of the stannane-vinyl  iodide (317)  (39 mg, 0.078 mmol) i n 0.5 mL of dry aceto-  n i t r i l e was added a 2 mL a c e t o n i t r i l e solution of palladium(O)  and  in  mixture  gave  ether;  generated  Concentration  of  an o i l , which was subjected to column chromatography  (Pasteur pipette) on s i l i c a gel (2 diethyl  situ  the reaction mixture was s t i r r e d at 6 5 - 7 0 ° C for 30 h.  T i c analysis of an aliquot showed two d i s t i n c t spots. the  vinyl-  17:1).  The  g,  elution  with  petroleum  ether-  fractions containing the less polar mate-  - 307 r i a l ( s ) were found to contain a mixture of unidentified compounds. fractions trated. Torr)  containing  the more polar compound were combined and concen-  The residual o i l was d i s t i l l e d (air-bath temperature affording  9.5  mg (55%) of the triene (318).  exhibited i r ( f i l m ) : 1728, 1.75  (s,  The  50°C/0.05  This colorless  oil  1639, 1165 cm" ; H nmr (400 MHz, CDCl )  6:  1  l  3  3H, v i n y l methyl), 1.79  (ddd, IH, J - 12, 10, 8.5 Hz), 2.15  IH, Hg, J - 16 Hz), 2.36  (dd, IH, H , J - 12, 6.5 Hz), 2.52  -  (d, IH, H , J - 16 Hz), 2.81-2.96 (m, 3H),  (s, J 6.5  17,  8, 3.5 Hz), 2.75  3H, -OMe), 5.00  Hz).  Exact  (ddd, IH,  D  (ddt, IH, H ,  B  Mass  (br s, calcd.  IH, Hp), 5.74 for  C H 0 1 4  1 8  2  A  (ddt, IH, H , J - 17,  10,  c  (M+):  J  3.59  E  (ddt, IH, H , J - 10, 2, 1.5 Hz), 5.03  «= 17, 2, 1.5 Hz), 5.39  (d,  218.1307;  found:  218.1306.  Preparation of (2-trimethvlstannyl-l-cyclopentenyl)methanol  To a cold ( - 7 8 ° C ) , s t i r r e d solution of the ester (205)  (323)  (2.83 g,  mmol) i n 60 mL of dry d i e t h y l ether was added 24.0 mL (24.0 mmol) 1M  s o l u t i o n of DIBAL i n hexane.  h and at 0°C for 2 h. added  The mixture was s t i r r e d at -78°C for 1  Saturated aqueous ammonium chloride (-3  mixture  mL)  was  r e s u l t i n g white s l u r r y was treated with anhydrous magnesium sulfate  and  filtered  was  a  The  then  the  of  allowed to warm to room temperature.  was  and  9.56  through a short column of F l o r i s i l .  The column was  - 308 eluted  with  eluate,  followed by d i s t i l l a t i o n (air-bath temperature  of  further  volumes  of ether.  Concentration of the combined 55°C/0.05  Torr)  the o i l thus obtained, afforded 2.506 g (100%) of the alcohol (323).  This c o l o r l e s s o i l exhibited i r (film): 3343(br), %  nmr  (t,  IH, -OH, J - 6 Hz), 1.88  4.23  (270  MHz, CDCl ) 6: 0.16 3  (s,  (quintet,  (d,2H, CH 0H, J - 6 Hz).  1619,  9H, -SnMe , 3  2  J  S n  1055,  -H "  5  770 4  H z  cm ; 4  )•  1  -  2  9  2H, J - 7 Hz), 2.37-2.51 (m, 4H),  Exact Mass c a l c d . for C H 0 S n (M+-CH3):  2  g  15  247.0145; found: 247.0153.  Preparation of (2-iodo-l-cvclopentenvl)methanol  To a s t i r r e d solution of the mmol)  in  (324)  vinylstannane  (323)  (2.50  The mixture was s t i r r e d at room temperature  purple color p e r s i s t e d .  until  ether). of  distillation oil  Concentration of the combined eluate,  Me SnI 3  (air-bath  (air-bath  a  pale  The solution was concentrated and the r e s u l t i n g  o i l was passsed through a short column of basic alumina (10  lation  9.564  70 mL of dry dichloromethane was added s o l i d iodine (2.455 g,  9.57 mmol).  with  g,  temperature  temperature  afforded 1.88 g (88%) of  the  g,  elution  followed by d i s t i l -  30-40°C/0.05  Torr)  then  7 5 - 8 0 ° C / 0 . 0 5 Torr) of the residual  iodide  (324).  This  colorless  oil  exhibited i r ( f i l m ) : 3310 (br), 1639, 1034 cm" ; H nmr (270 MHz, CDC1 ) 1  X  3  6: 1.46  (t,  IH, -OH, J - 7 Hz), 1.98  (quintet,  2H, J - 8 Hz),  2.39-2.52  - 309 (m,  2H), 2.62-2.75 (m, 2H), 4.15 (d, 2H, -CH 0H, J - 7 Hz).  c a l c d . f o r C H O I (M+): 223.9700; 6  found:  9  To 2.816  a  cold  (-20°C), s t i r r e d  added i n v e r y solution  was added 145 A * L (2.82 mmol)  a pale yellow color persisted.  small  of  (325)  s o l u t i o n o f t r i p h e n y l p h o s p h i n e (738 mg,  mmol) i n 11 mL o f d r y dichloromethane  bromine u n t i l  portions  until  the  T r i p h e n y l p h o s p h i n e was  solution  was and  had  petroleum  ether  s l u r r y was p a s s e d ether).  (10  mg  ir  (film):  (quintet,  the  The s o l u t i o n was  mL) was added t o the r e s i d u e .  A  dropping  concentrated The r e s u l t a n t  (5 g, e l u t i o n  50-55°C/0.05 T o r r ) o f the r e s i d u a l  -1  J  found:  with  o i l afforded  This colorless o i l exhibited  1627, 1431, 1209, 920 c m ; H nmr (300 MHz, CDCI3) 2H,  mixture  C o n c e n t r a t i o n o f the e l u a t e , f o l l o w e d by d i s t i l l a t i o n  (80%) o f the iodo bromide (325).  Hz), 4.08 ( s , 2H, 285.8856;  After  through a s h o r t column o f F l o r i s i l  ( a i r - b a t h temperature, 648  clear.  been r i n s e d w i t h 1.0 mL o f d r y CH2CI2, the r e a c t i o