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Synthesis and reactions of a 2-cyclopenten-1-one d³ synthon Nadarajah, Sivakumar 1986

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SYNTHESIS AND REACTIONS OF A 2-CYCLOPENTEN-1 -ONE d  SYNTHON  3  by  SIVAKUMAR NADARAJAH B.Sc,  A  University  THESIS THE  of  P e r a d e n i y a , S r i Lanka, 1980  SUBMITTED  IN P A R T I A L  REQUIREMENTS MASTER  FULFILMENT  FOR THE DEGREE OF  OF  OF  SCIENCE  in  THE  FACULTY  OF G R A D U A T E  (Department  We  accept to  THE  this  of  UNIVERSITY  Chemistry)  thesis  the required  STUDIES  as  conforming  standard  OF BRITISH  COLUMBIA  April 1986 ©  Sivakumar  Nadarajah  00  In  presenting  degree it  at  the  freely  of  copying without  copying my or  my  thesis  in  University  available  extensive head  this  for of  of  this  publication  thesis or  of  fulfilment  British  reference  department  written  partial  by this  of  Columbia,  I  and  study.  for  scholarly  his  I  the  requirements  agree  that  further  the  agree  purposes  her  representatives.  thesis  for  financial  gain  Library that  may  or  for  It  The 1956  University Main  Vancouver, V6T  of  1Y3  Mall Canada  shall  be  granted  is  understood  shall  not  be  by  make for the that  allowed  permission.  Chemistry of  advanced  permission  SIVAKUMAR  Department  an  British  Columbia  NADARAJAH  ABSTRACT  This  thesis  describes  the  penten-1-one  14  to  3-iodo-2-cyclopenten-1-one  convert  observations cuprate  v i a the higher  preparation  made  from  formation  convenient  this  which  thesis  also  species  describes  species,  and  transmetalation  reaction  of  of  corresponding  with products  Treatment or  cuprous  of  reagents  reagent  105  solution  of the  enones  in g o o d  at  w a s made at  84 latter  such  corresponding  as  by  -78°C.  reagent  addition  by  with  conjugate  108  a n d 109  of  copper  75  103  in  in excellent  a  h  yields.  1  reagents  a n d 107  106  of  "one-pot"  and  practically  methods.  3-te/7-butyldimethyl-  into with  the  corresponding  electrophiles. produced  and  and  with  84 gave  respectively.  3-iodo-2-cyclopenten-1-one the cuprate  1  2-cyclopenten-1-one  products  of  traditional  reacted  aldehydes,  for  The  catalyzed  with  viable  The  1—lithio—  smoothly  at  ketones,  Thus,  -78°C  providing  in the  yield.  -78° C  a n d 104,  103  a  reagent  which  84,  halides,  the vinyllithium  cyanide  cuprate  sense,  alky I  be  prepared  product.  development  conversion  latter  n e w reagent desired  methyllithium  3-terf-butyldimethylsiloxycyclopentene tetrahydrofuran  to  its  with  83  the  preparation  83, the  the  compared  the  siloxy-1-trimethylstannylcyclopentene lithio  led to  a  78,  to  75  demonstrated  such  3-trimethy!stannyl-2-cyclo-  stannylcuprate  chemistry  was  w a y t o generate  This  order  of  1 equiv.  solutions  Similarly equiv.  thus (I)  of  of  of  the  the corresponding magnesium  produced  reacted  bromide in  2-cyclohexen-l-one,  in e x c e l l e n t  yields.  /9-lodo  3-iodo-2-cyclohexen-1-one to  give  The cyanocuprate  ii  corresponding  bromide-dimethylsulphide  and  sense  phenylthiocopper  a  prepared  to the conjugate  complex, affording  enones 7  also  the corresponding  104  Grignard  by  a  such  to the as  reacted products "one-pot"  process  also  in  yield.  good  reacted  with  3-iodo-2-cyclopenten-1-one  75  to  give  the  enone  108  LIST OF SCHEMES Schemes  P a  9  e  Scheme  1  3  Scheme  2  4  Scheme  3  5  Scheme  4  7  Scheme  5  1 0  Scheme  6  1 2  Scheme  7  1 6  Scheme  8  1 7  Scheme  9  1 8  Scheme  10  2  Scheme  11  2 1  Scheme  12  3 3  Scheme  13  •  IV  0  3 4  LIST OF ABBREVIATIONS  AIBN  Azobisisobutyronitrile  Bu  Butyl  br.  broad  "C  nmr  carbon-13  nuclear  calcd.  calculated  cat  catalytic  DIBAH  Diisobutylaluminum  DMF  magnetic  hydride  A^AZ-Dimethylformamide  E*  electrophile  Et  Ethyl  ether  Diethyl  equiv.  equivalents  glc  gas-liquid  h  hour  HMPA  Hexamethylphosphoramide  MH n m r  proton  /  iso  ether  chromatography  nuclear  ir  infrared  Me  Methyl  min  minutes  Ms  Methanesulfonyl  M  molar  n  normal  Nuc-  nucleophile  Ph  Phenyl  Pr  Propyl  rt  room  t  resonance  o r tert  magnetic  resonance  temperature  tertiary  tic  thin-layer  chromatography  THF  Tetrahydrofuran  THP  Tetrahydropyranyl  TMS  Tetramethysilane  Ts  p-Toluenesulfonyl  v  LIST OF GENERAL PROCEDURES  Procedure A  page Preparation  of  1-lithio-3-fe/'f-butyl-  dimethylsiloxycyclopentene reaction B  Preparation its  its  electrophiles  with  a,^-unsaturated  0-iodo-a,/3-unsaturated  Preparation  and its  of phenylthiocuprate  reaction  and C  with  84  55  of the cyano  reaction with  enones  and  103  60  ketones  ketones  cuprate  104  and  61  and 0-iodo  enones D  Preparation from  84  conjugate  of the Grignard  and its copper addition  to  vi  reagent  105  (I) c a t a l y z e d  enones  62  ACKNOWLEDGEMENTS  My  sincere  thanks  and  encouragement  him  f o r the opportunity  current  work  I  Jung  this  like  their  also  of  f o r his guidance,  this  work.  a n e w area  assistance,  I would  also  of tin chemistry  like  patience to  which  thank  made the  and worthwhile.  the members  understanding  M r . P. M a r r s ,  of  and help,  Dr. Piers'  especially  a n d helpful  research  Dr. J . M .  assistance  Mr. A. T s e and Miss.  on  group,  Chong  many  A . Yeung  past and  a n d Dr.  G.L.  occasions.  My  for  proof-reading  thesis.  I  would  students thanks  like  to  thank  of the Department t o Dr. R.E. P i n c o c k  assistance services  of  are gratefully  Canadian  The  able  importantly aberration  spectra,  I  thank  from  of  this  my  their  members  support  and fellow  and friendship.  and encouragement.  glass  a healthy  the  blowing,  University  Education  thesis  mother  o f m y adulthood.  and provided  staff  graduate  M y special  The skillful  electronic  and  technical  mechanical  acknowledged.  f o r International  typing  Faculty,  f o r h i s help  assistance  Bureau  the  w h o offered  nmr, mass  Financial  me  to explore  encouragement  to  Piers  the course  t o thank  f o r their  for  thanks  during  s o interesting  would  present,  t o Dr. E d w a r d  by  is gratefully  family  m y thanks  counterpoint  British  for  and the  their  is appreciated. support  t o all m y friends  to m y academic  vii  Columbia  acknowledged.  Mr. S. Maheswaran  and m y  Finally,  of  during  Most this  w h o encouraged  adventures.  DEDICATION  This  thesis  is  dedicated my  to  father  the  memory  of  "If if  you do the experiment  you may not be certain to get an answer, but  you don't do it you can be certain not to get one."  Lord  Howard  Florey  (1898-1968)  ix  X  TABLE OF CONTENTS  ABSTRACT  ii  LIST  OFSCHEMES  iv  LIST  OFABBREVIATIONS  LIST  OFGENERAL  v  PROCEDURES  vi  ACKNOWLEDGEMENTS  vii  DEDICATION LIST  viii  O FT A B L E S  xiv  INTRODUCTION  '.  1.1  General  1.2  Previous  1.3  The  1.4  1 1  work  6  problem  8  Selected recent reports equivalents (Method B )  concerning  cyclic  0-acylvinyl  anion 11  (a) Using  $-acylvinyl  halo reagents:  11  (bl  $-acylvinyl  tin  18  Using  reagents:  DISCUSSION 2.1  23  Preparation  of 3-trimethylstannyl-2-cyclopenten-1-one  2.1.1  Preparation of  2.1.2  Reaction of enone 75  the higher  the higher  order  order  23  14  26  cyanocuprate 78  cyanocuprate 78 with  the  fi-iodo 27  2.2  Preparation  of 3-trimethylstannyl-2-cyclopenten-1-ol  2.3  Preparation  of 3-fe/-?-butyldimethylsiloxy-1-trimethylstannylcyclopent-  ene 2.4  2.5  83  Preparation its  29  81  31 o f 1-lithio-3-rerr-butyldimethylsiloxycyclopentene  reaction  Conjugate  with  addition  84  and  electrophiles o f cuprate  32 and  Grignard  1-lithio-3-terr-butyldimethylsiloxycyclopentene  xi  species  derived  84 t o e n o n e s  from 38  EXPERIMENTAL  44  3.1  General  3.2  Solvents  3.3  Typical 3.3.1  information and  44  reagents  procedures  46  for  the  preparation  o f trimethylstannyl  Preparation  of  trimethylstannyl  3.3.2 Preparation  of  lithium  (phenylthio)itnmethylstannyl  3.3.4  of  lithium  (cyano)ftri methyl stannyl jcuprate  Preparation  3.3.5  Preparation  of  di lithium  reagents  ... 4 8  lithium  48 )cuprate  8  49  74  ( cyanojfmethy I ){tri methyl stannyl )cuprate  78 3.4  3.5  50  Preparation 3.4.1  of 3-trimethylstannyl-2-cyclopenten-1-one  Using  Large  the higher  scale  preparation  order  50  14  50  cyanocuprate 78  of  3-trimethylstannyl-2-cyclopenten-1-one  14  51  3.5.7 3.6  Using  Preparation 3.6.1  the phenylthiocuprate  51  8  of 3-trimethylstanny!-2-cyclopenten-1-ol  Small  52  81  52  scale  53  3.6.2 Large scale 3.7  Preparation ene  3.8  of 3-ferf-butyldimethylsiloxy-1-trimethylstannylcyclopent-  83  General  54 procedure  Preparation 3.9 3.10 3.11  3.12  of  A  55  1-lithio-  3-tert-butv I d i methyl si I oxycycl opentene  84 and  its reaction with electrophiles Preparation o f 1-/?-butyl-3-te/-f-butyldimethylsiloxycyclopentene Preparation o f 1-[ 2-(2-cyclopentenyl)ethyl o x y c y c l o p e n t e n e 97 Preparation  of  cyclopentene  98  Preparation cyclopentene  3.13  49  Preparation  of  96  55 56  ]-3-ferr-butyldimethylsil57  1-(1-hydroxycyclohexyl)-3-terr-butyldimethylsiloxy58 l-O-hydroxycyclopentyl^S-terf-butyldimethylsiloxy58  99 o f 1-[  1-hydroxy-2-(2-cyclopentenyl)ethyl]-3-ter?-butyl-  dimethylsiloxycyclopentene  100  xii  59  3.14  General  procedure  B  60  Preparation of the phenylthiocuprate 103 and its a p-unsaturated ketones and p-iodo-a,p-unsaturated 3.15  General  procedure  Preparation  of  3.16  General  3.17  Preparation pentanone  3.18  104 and  its  reaction  with  enones 61  D  62  reagent  conjugate addition of  105 from  84 and its copper  (I)  to enones  62  3-(3-rerf-butyldimethylsiloxy-1-cyclopentenyl)cyclo63  106  64  the phenylthiocuprate  3.17.2 Using  the cyanocuprate 104  64  3.17.3 Using  the Grignard  64  Preparation  3.75.7  of  103  reagent 105  3-(3-terf-butyldimethylsiloxy-1-cyclopentenyl)cyclo6*5  107  Using  the phenylthiocuprate  103  65  3.18.2 Using  the cyanocuprate 104  66  3.18.3 Using  the Grignard  66  Preparation  of  cyclopenten-1-one  3.20  cyanocuprate  3.17.1 Using  hexanone  3.19  61  of the Grignard  catalyzed  60  enones  procedure  Preparation  with  C  the  and p-iodo  reaction ketones  reagent 105  3-(3-fe/-r-butyldimethylsiloxy-1-cyclopentenyl)-2— 66  108  3.19.1 Using  the phenylthiocuprate  3.19.2 Using  the cyanocuprate 104  Preparation of cyclohexen-1-one  3.20.1 Using  103  67  3-(3-terf-butyldimethylsiloxy-1-cyclopentenyl)-2— 109  the phenylthiocuprate  REFERENCES  67  103  67  68 69  xiii  LIST OF TABLES Table  Page  Table I: cuprates  Reaction  of  the  ^-iodo-a.^-unsaturated  ketone  75  with  organotin 24  Table II: R e a c t i o n electrophiles  of  1-lithio-3-teri'-butyldimethylsiloxycyclopentene  84  with 36  Table III: Reaction of the cuprates with enones and /S-iodo enones  and  103  104  and  the  Grignard  reagent  105 42  Table  IV:  Purification  of  solvents  and  reagents 47  xiv  INTRODUCTION  1.1  General  During increased ago.  to  their As  extent  of  utility  knowledge  have  been  organic  occupied  practicing  mainly  a result, the 0-carbon  nucleophiles  of  time  from  our  would  classes  for some  attention  synthetic  century,  which  the various have  share  twentieth  an  Among  compounds fair  the  a special  organic  system  synthons can  be  ethers  1  to  1  This  attack  behave 3  years  carbonyl received  compounds double  is an acceptor  a  owe bond.  site f o r  }  O©  synthetically  prepared  [3], enol  in  starting good  phosphates  compounds  family  suitable  substituted  [1]. T h u s ,  carbonyl  important  of  compounds  substances  These  has  and free r a d i c a l s , but not f o r electrophiles.  synthesis.  carbonyl  hundred  the carbon-oxygen  the a.^-unsaturated  0-Alkylated-a,/9-unsaturated  nucleophilic  a  o.jS-unsaturated  chemists.  of  chemistry  position, a n d have  O  organic  organic  inconceivable  molecules,  t o the presence  of  of  of  a  yields [4], enol  of  1,3-dicarbonyl via  the  acetates  is  (cf.  on species  the /9-acylvinyl compounds  corresponding [5], thioenol  precursors  in  prepared  by  usually  reagents  0-heteroatom  as equivalents from  are useful  compounds  organometallic with  1  Q./9-unsaturated 2).  T h e latter  cations  or a  4, t h e a l k e n o n e s  enaminones ethers  [2],  [6] a s w e l l  3  1  enol as  C o r e y defines synthons as "structural units within a molecule which are related p o s s i b l e s y n t h e t i c o p e r a t i o n s " [E. J . C o r e y , Pure. Appl. Chem., 14, 19 ( 1 9 6 7 ) ] .  1  vinyl  halides  [7]  total  synthesis  (equation  of  more  1). T h i s  complex  4  there  have  a,/9-unsaturated  systems,  these  To  systems. may be  normal  molecules  successfully  achieved  [donor  one must  [acceptor reactivity  2  nucleophilic  [1], w h i c h of  the  2). T h i s  of  masked  as equivalents  methodology a,£-unsaturated  has  of  greatly  carbonyl  reativity".  realized  of  atom  into  through  the  E  o,/3-unsaturated  carbonyl  the ^ - a c y l v i n y l  anions  extended  on  conversion  ^-carbon  can be  on  attack  "normal  involves  2  of  attack  electrophilic  the pattern  character  (equation  of  t o attempt  reverse  umpolung"  (a)]  3  intermediacy  examples  be interesting  v i a "reactivity  (d)]  t o the  [8-10].  numerous  it w o u l d this  applied  1  been  effect  electrophilic  nucleophilic  behave  has been  2  Although  This  strategy  the  (or or  synthesis  d  3  latent) synthons and  compounds, 5.  This  synthetic  which type  utility  compounds.  H e t e r o a t o m s , p r e s e n t in m a n y o r g a n i c m o l e c u l e s ^ jjmpose a l t e r n a t i n g a c c e p t o r p r o p e r t i e s ( a t t a c k b y d o n o r s p e c i e s ) a t carbons C ' ' "', a n d d o n o r properties (attack b y a c c e p t o r r e a g e n t s ) at c a r b o n s C ' the heteroatom itself being a d o n o r c e n t e r (d°), s e e r e f e r e n c e 1. 2  2  of of  where  Y  =  C N , NO,, S P h , SO,Ph  ; RX  =  alkyl  Scheme In  recent  development extensive in  years  and  survey  general,  four  use of  there  have  of  synthetic  these  strategies  reports  been  halide  1  a  number  equivalents  is beyond  [11] h a v e  been  of  of  concerning  /9-acylvinyl  the scope  employed  reports  of  this  anions thesis .  An  However,  3  t o generate  5.  the  ^-acylvinyl  anion  equivalents.  In  one  (Method  system  is  (cyano  [12], nitro  [17]),  3  activated  the resulting  For reviews  A),  the  toward  /3-position  proton  on this  subject,  is  a  abstraction  [13], phenylseleno carbanion  of  by  latent an  [14], phosphino  reacted  with  see reference  3  an  11.  a,£-unsaturated  electron  withdrawing  [15], thio  electrophile,  carbonyl  [16]  and the  ,  group sulfonyl  activating  group  is  subsequently  (Scheme  Y  X  X=  to  introduce  dithiocarbamate, E  +  =  alkyl  halide  sulfoxide  or  selenoxide  The described carbonyl  For  required  unsaturation  [18]  second in  this  group  reports  synthesis,  see  method thesis,  via  of  acyclic  Y  =  S  or  Se  and  2  (Method  B)  involves  generation  lithiation  references  where  (electrophile)  Scheme  4  the  1).  = 0;  eliminated  of  a  counterparts 19b,  21d-e,  which  vinyl  has of  a  close a  substituent  used and  mainly 22.  4  in  relationship  donor 4  center  (halo  the  f)-  [19-20],  field  of  to to  the  work  a  latent  trialkylstannyl  prostaglandin  [21])  followed  electrophiles  where  R  reaction  (Schemes  3  =  by  alkyl,  aryl;  4,  6,  E*  =  of and  the 7)  resulting  (vide  the  third  (dithiocarbamate deprotonated, activating introduce  [24],  the  group the  method  electrophile;  sulfoxide  resulting is  (Method [25])  M  and  with  an is  made become  =  Li; P  =  protecting  group  3  the  or  carbanion  subsequently  unsaturation  C),  compound  infra).  Scheme  In  organometallic  a -  position  Se-allyl  reacted  system  with  to  undergo  the  latent  of  an  an  an  (selenoxide electropile,  a l l y I ic  carbonyl  S—al ly I  system [26]) and  rearrangement  system  (Scheme  is the to 2)  [27].  s  of lic  F o r e x a m p l e s o f d i r e c t d e p r o t o n a t i o n o f , (a) h e t e r o a t o m a c t i v a t e d / ? - v i n y l c e n t e r m a i n l y a . ^ - u n s a t u r a t e d a c r y l i c a c i d d e r i v a t i v e s , s e e r e f e r e n c e 2 3 ; (b) p r o p a r g y ethers, see reference 22b.  5  The  fourth  carbanion allenyl  1.2  method  to  0-  a  precursors  Previous  latent  carbonyl  followed  by  D)  involves  group  reaction  from with  the  work  in  ^S-iodo-a,^-unsaturated cations  (a  3  our  heteroatom  2  synthons)  3  =  Br,  [7]  had  as  which A  reaction  alkyl  of  an  allenic  propargyl  (Scheme  or  3).  are  excellent  cuprates, halide  certain  number  of  the  synthesis  of  /?-bromo-  synthetic  and  equivalents  of  [8-9].  3 enones  with  2  afforded,  in  has  replaced  these  that  I  £-halo  organic  for  the  [28]  shown  2  such  of  substituted  electrophiles  laboratories  ketones  X  Thus,  generation  work  Previous  /9-acylvinyl  (Method  been  variety  excellent  ^-substituted  functionalized  yields,  by  a  enones  five  nucleophilic  ^-substituted  nucleophilic have  6  [8b]  of  and  enones  species  proven  seven  to  [8c]  reagents, 6,  in  (equation  3).  be  very  membered  useful ring  systems.  We  were  also  intrigued  as  suitable  precursors  5.  It  found  was  a.yfl-unsaturated  that  ketones  of  by  the  synthetic  this [21a]  could  possibility equivalents  be  (Scheme  that of  successfully 4).  6  0-halo  enones  /9-acylvinyl achieved  anions via  2  might (d  3  serve  synthons)  ^-trialkylstannyl-  1) 2)  LDA f-BuMe,SiCI HMPA  v  12 where  E*  =  13  electrophile  Scheme  4  Thus,  3-iodo-2-cyclohexen-1-one  (phenylthio)(trimethylstannyl)cuprate transformation, yield.  This  to  material  transmetalation The  latter  with  a  1.3  [30]  number  of  were  extended Firstly,  to it  a  into  the  to  This  nucleophilic  to  reagent  afford  new  silyl  anion  dienes  to  £-halo  equivalent  was  which  10  (d  were  this  excellent underwent  species  synthon),  3  to  11.  reacted  hydrolyzed  complementary  enones  for  in  9  vinyllithium  which  lithium  developed  ether  the  12  methodology  additions  enol  produce  ^-acylvinyl  electrophiles  lead of  dianion  17,  (equation  likely  to  in  cyclic  would  15  instead  interested other  was  ether  probably  would  is  13.  new  with  3-trimethylstannyl-2-cyclohexen-1-one  methyllithium  which  a  smoothly  to  the  the  earlier  [8].  problem  We  enol  [29],  8  converted  with  enones  involving  The  was  reagent,  ^-substituted work  produce  reacted  7  that be  5).  lead  futile,  (equation  treatment if  to  of  this  regiochemical  whether  especially of  since  deprotonation  However to  systems, protection  transmetalation  upon  determining  the  4).  15  with  were  to  ambiguity  One  two be in  8  with (a  16  could  system base  successful,  the  products,  as  14  the  alkyllithium)  the  formation  base  (e.g.,  addition which  was  of  be  analogues.  cyclopentadienyl  envisage  of  could  ring  of  (e.g.,  "stable"  equivalents  the  methodology  f ive-membered  carbonyl  treatment yield  similar  silyl would anion)  of  the  alkyllithium) electrophiles  not  desirable.  Hence  it s e e m e d  synthon.  likely  Therefore,  that  the dianion  the method  would  17  6  o f protection  o f the carbonyl  15 involve  formation  trialkyltin group  The  of  0-trimetnylstannyl d  3  synthon  group  of  which  after  14  the  resultant  produce or  21  extending enone 5.  should  system  Presumably,  it might  7  d  3  electrophilic  chosen  not involve  a n acid  above  this  in this  useful  d  3  should n o t  would  t o yield  reagents  species  would  6  the  use  protection 5 . path d  3  the carbonyl  5 , path  dianion  after  A ) t o give  synthon  B). Treatment  towards  equivalent o f  group  removal  of the  o f the carbonyl  20. T r a n s m e t a l a t i o n  afford,  For successful manipulation o f a related (±)-coriolin, s e e reference 3 1 .  w a s t o investigate t h e  the desired  t o reduce  21' ( S c h e m e  catalyst.  to  [32] (Scheme  since the  the carbonyl  o f a synthetic  involve  produce  b e possible  synthon  precursor  Secondly,  t o protect  thesis  methodology  conditions  [30] w o u l d  function  the molecule.  any method  14 a s a p o t e n t i a l  transmetalation  alcohol  within  described  the  non-acidic  thedesired with  labile,  o f t h ework  under  Alternatively,  system  is acid  t o transmetalation  possibility  the  o f t h e diene  objective  as a  17  functionality  prior  n o t serve  18  19.  and o f 20  protect would  o f either  19  o f the protecting  the total  synthesis o f  F o r other m e t h o d s o f f o r m i n g C - C b o n d s using vinyltin reagents, s e e (a) W.F. G o u r e , M . E . W r i g h t , P . D . D a v i s , S . S . L a b a d i e , a n d J . K . S t i l l e , J. Am. Chem. Soc, 106, 6 4 1 7 ( 1 9 8 4 ) ; ( b ) J . E . B a l d w i n a n d D . R . K e l l y , J. Chem. Soc, Chem. Commun., 682 (1985). 7  • For similar five membered d synthons, see species s p e c i e s 60 (cf. r e f e r e n c e 2 1 b ) (vide infra). 3  9  49 (cf.  reference  20b) and  p  M  =  SnMe  21 M  =  Li  20  Scheme  group,  the  In also  ^-substituted  addition  to  interested  in  corresponding Michael  Clearly earlier source  novel  22  or  its  reaction  of  19  the  of  these  studies of  the  cuprates.  addition  enone  the  possibility If  this  cuprates  proposed  [21a] and  would  to  to  viable  with  21  converting be  and  masked  related  5),  one  reagents could  we  were  into  the  investigate  the  compounds.  successful,  /?-acylvinyltin  ^-acylvinyl  10  if  electrophiles,  these  successful,  (Scheme  establish  synthetically  and/or  enones  reactions  5  equivalent.  of  were  3  anions  (d  3  coupled  with  compounds synthons).  as  our a  Selected  1.4  (Method  recent  reports  concerning  cyclic  j?-acvlvinvl  anion  equivalents  B) '  (a) Using  $-acylvinyl  halo reagents:  OP  O  CuLi X  =  R  Br. I  23  2  Since into  the development  £-halo-a,£-unsaturated  number  o f groups  synthons.  Recently  however,  reagents  accomplish,  has been  These  using 6, the  sodium  the procedure  Scheme latter  resultant resulted the  followed  vinyllithium  with  29  followed  by  of  [33], gave  0-acylvinyl  anion  with  into  the mixed  w e wished t o  the cyclic of  a  variety  of  £-iodo  enones  24  the resulting  the silyl  of  with cuprate  treatment  f-butyllithium.  alcohols 2 5 ,  ethers  of 2 6 w a s accomplished  t w o equivalents  o f the mixed  by a  substances  smoothly  b y protection  27  ^-diketones  employed  t o the o n ewhich  reacted  reduction  exchange  been  o f cyclic  o f these  similar  b y Corey  reagents  in the formation  have  of  6 ) [19a].  23  For example,  6). L i t h i u m - i o d i n e  benzoate  (Scheme  developed  substances  quite  reagents  borohydride,  f o r conversion  [7], t h e latter  the conversion  reported  reagents.  2  method  f o r the preparation  23, a process  vinylcuprate  electrophilic  ketones  [19a, 20a-b]  vinylcuprate  with  o f a general  26  (equation  b y treatment Treatment  of  o fthe  3-methoxy-3-methyl-1-butynylcopper reagents of  the  2 8 . Reaction resultant  o f 2 8 with  mixtures  with  This brief account i s n o t meant t o b e exhaustive, but i s given o n l y t o p r o v i d e the reader w i t h s o m e b a c k g r o u n d i n this area. T h e e x a m p l e s w e r e c h o s e n f o r their c l o s e relationship t o t h ew o r k d i s c u s s e d in this thesis. F o r other reports o f related ^ - a c y l v i n y l anion equivalents s e e references 19-21. 9  11  where  R  =  H  or  Me;  L=  —C=C—C(Me) OMe 3  Scheme  12  6  tetra-/?-butylammonium  fluoride  conversion  the  these  of  into  30  transformations  gave  the  alcohols  corresponding  should  pose  no  30  enones  problem  1 0  OSiR  in  excellent  was  31  not  yield  [19a].  attempted.  The  However  .  OSiR  OSiR  34  35  X  32 33  X  =  Br,  X  =  Li  Protection enol the  silyl  the  of  ethers  protected  envisaged  7  I  the  species  [21a].  to  proved  to  the  be  to  32  However, enol  produce  Furthermore,  followed  32,  corresponding  failed  carbonyl  by  of  attempts  silyl  ether  was  For  y9-iodo  a  number enones  the  33,  convert  34,  under  useful  contaminated  of  2  exchange  as  the  (e.g.,  equivalent  corresponding alkyllithium)  of  5,  has  3-iodo-2-cyclohexen-1-one variety  yields with  of isomer  of  experimental  the 35,  desired  of  been 7  into  conditions, product  and  these  38  (17%)  34.  compounds  unstable.  37  as  enones  synthetic  to  36  10  £-halo  lithium-halogen  produce  synthetically  product  quite  group  related  examples  precursors  to  (of  (68%)  cuprates)  /9-acylvinyl  13  anion  involving  the  equivalents,  use  see  of  acyclic  reference  19b.  Recently be  used  as  Swenton ^-acylvinyl  from  these  studies  was  found  to  example,  double-bond this  anion  equivalent,  migration  exchange  37  11  a  that  of  does  is 37  (68%)  37  0-bromo  number  limitations.  of  amounts  it  cannot  synthetically required  (equation  and  bisketal  accompanied  two  be  a  38  undesirable equivalents  the  limitation a  (cf. of  projected Scheme  the  First,  Due  (equation on  its  study 8).  alkylUthium  (equation  to  severe does  the  (cf.  use  as  effect  step  7).  For  controlled problems  not  a  in  serve  to  system,  species  which  Furthermore, to  derived  parent  7)  in  can  ketalization  carefully  chemistry for  enones  chemistry  the  under  (17%).  ketalization  in  0-bromo  bisketal  Secondly,  serious used  the  gave,  36  of  However,  of  cyclopentenones,  impose  ketals  [20a].  cyclopentenones.  not  glycol  equivalents  substantial  isomerization  While  in  produce  funtionalized  species  anion  revealed  monoketal  ketalization  prepare  reported  al.  3-bromo-2-cyciohexen-1-one  conditions, the  et  37) . u  ^-acylvinyl double-bond  the  protected  lithium-halogen  8) . 1 5  39  13  The ketalization of C - 2 substituted c y c l o h e x e n o n e c o m p o u n d s g o o d y i e l d s in w h i c h the d o u b l e - b o n d i s o m e r i z a t i o n did not  furnished occur.  ketals  A p p a r e n t l y , ^ - e l i m i n a t i o n is m o r e r a p i d than m e t a l - h a l o g e n e x c h a n g e . For where deprotonation is c o m p e t e t i v e w i t h m e t a l - h a l o g e n e x c h a n g e , see J . S . S w e n t o n , D . K . A n d e r s o n , D . K . J a c k s o n , a n d L. N a r a s h i m a n , J. Org. Chem., 46, (1981). 12  14  cases 4825  Third, acid the  while  hydrolysis case  of  (equation  9).  in  most  conditions  the  product  cases,  no  rearrangements  employed derived  in  from  the use  of  partially  alleviated  standard  conditions,  equivalent  of  catalyst,  the  obtained  in  n= n=  (equation  the  carbonyl  some when  ethanedithiol desired good  of  the  in  with  via  problems  /?-bromo  0-bromo yields,  group  the  enones presence  enone  rearrangement  cyclohexenone  dithioketalization mentioned  36 1 41  and  36 of  under was  as  the  mild  observed  an  in  electrophile  44  Importantly,  this  process  resulted  15  [20b]. treated  enones  Under  the  with  one  trif luoride-etherate and  and  42 ( 9 0 % ) 43 (76%)  £-bromo  were  41  42  of  above  boron  dithioketals  bisdithioketals  2  10).  of  noted  40  37  Protection  work,  were  43,  respectively, as  45  minor  as  a  were  products  44 45  in  no  double-bond  isomerization  in  the  of  desired  the  monoketals  0-bromo  metal-halogen addition  of  standard  set  six-  enones  exchange the  S  at  45.  -78°C  As  systems  a  was  with  The  electrophiles ring  and  dithioketals  electrophile.  of  membered  44  result,  the  carried  one  out  equivalent  reactions  of  these  good  yields  of  gave  (Scheme  functionalization in of  the  standard  alkyllithium  lithiated products  chemistry fashion:  followed  dithioketals for  both  with  five-  by a and  7).  S 1)  /?-BuLi  2)  Cyclohexenone  42  46  (92%)  HgClj-HgO CHjCN/ H 0 2  Jones'  47  However, dithioketal  46  reagent  Scheme  as  in  on  hydrolysis  oxide  in  acetonitrile/  gave  the  symmetrical  the  water  case  of  with  product  47  acetal a  yielded  7  the  mixture  37  (equation of  rearranged  (Scheme  16  7).  mercuric product  40  (78%)  9),  the  chloride 40,  which  corresponding and  mercuric  on  oxidation  48  50  Mel  51 Scheme  Paquette construction ketone  by  furnished, (Scheme 52  and  of  Metal-halogen  albolic  addition  intermediate  The  used  ophiobolin  sequential  via 8).  have  al. the  [20d].  48  followed  et  close  acid  53  50,  this  self  using  exchange the  the  relationship is  methodology  nucleus  of  8  of  51  apparent.  17  rapid  and  efficient  dithioketal  49  and  the  the  dithioketal  43  at  -78°C  crystalline to  the  the  epimerically  single of  for  pure  48  ketone  sesterterpenes  and  methyl in  51  such  bicyclic  as  71%  [20b], iodide yield  ophiobolin  F  Me  OH 52  53  During developed  the in  our  course  of  our  laboratories  work, (cf.  other  Scheme  workers 4)  for  4-(tetrahydropyran-2-yloxy)-2-cyclopenten-1-ones to  the  one  preparation  which of  oxy)cyclopentene  we  wished  to  accomplish  the 62,  (Scheme  have  used  preparation via 5)  a  the  methodology  of  2-substituted  process  [21b].  They  quite  similar  described  the  (3S*,5R*)-1-lithio-5-(f-butyldimethylsiloxy)-3-(tetrahydropyran-2-yl60  from  the  chloro  18  cyclopentenone  54  and  the  stannyl  cyclopentenediol 55  derivative  reacted  13  efficiently  cyclopentenediol corresponding  this  59; with  derivatives  2-substituted  latent  3,5-dihydroxycyclopentenyl  various  61,  some  electrophiles of  which  to  were  form  substituted  converted  OTHP  N  into  their  4-(tetrahydropyran-2-yloxy)-2-cyclopenten-1-ones  O  f-BuMejSiO*  carbanion  SnBu,  f-BuMe,SiO  58  62.  OTHP  M  f-BuMejSid  69  M  =  SnBu,  60  M  =  Li  1  61  OTHP  62 The  addition  of  chloro  cyclopentenone  bis(tri-/?-butylstannyl)cuprate -25°C  gave  reduction  the of  1 4  stannyl the  stannyl  0.75 with  with  of  The  58.  a  variety  of  in  transmetalation  lithio  (2  in  equiv.)  at  electrophiles  to  in  lithium  to  was  substituted  yield be  the  from  For an alternative  protected  lithio  equivalent  cyclopentenes  of of  this type  anion,  5-hydroxy-3-oxocyclopentenyl,  a  3-hydroxy-5-oxocyclopentenyl  carbanions.  1 4  For  recent  developments  in this  /9-acylvinyl  area,  see reference  60 m a y also  reacted  within  efficiently  cyclopentenediol  anion, or  s e e reference  19  25a. Appropriately  be regarded  34.  the  troublesome.  derivatives 6 1 . 1 }  at  by  gave  accomplished  generated,  the  followed  group  found  this  6 0 , thus  yield  to  Stereoselective  58  94% overall  was  -45°C  cyclopentene  yield.  hydroxy!  59  step  84%  compound  newly-formed derivative  tetrahydrofuran)  t e t r a h y d r o f u r a n - d i m e t h y l s u l f ide  58  group  the  n-butyllithium  h. T h e i n t e r m e d i a t e  in  cyclopentenone  cyclopentenediol  enone  However,  equiv.)  carbonyl  tetrahydropyranylation (IRMS^J-stannyl  (1.1  (in  54  as  latent  These equivalent chloro  conversions were  55  enone  derivative chloro  by  into a  the  conjugate  cyclopentenone  54  3,5-dihydroxycyclopentenyl (Scheme  to  complementary  54  61  leading  the  to  3,5-dihydroxycyclopentenyl  the  previously  corresponding  alkyl  addition-elimination  was  shown  carbocation  to  conversion  substituted route  be  which  56  reported  [9].  synthetically  of  the  cyclopentenediol  In  undergoes  carbanion  this  process,  equivalent  nucleophilic  to  the the  alkylation  9).  \ 1)  BujSnMgCI  2)  MsCI  V OMs  SnBu,  64  63  K,C0 , 3  DMSO  V X  Scheme  Still  et  anion  synthon,  acetal  63,  of  [21c]  al.  via  have  carbonyl a  hitherto  prepared  protected unknown  tri-/7-butylstannylmagnesium  the  /9-acylvinyltin 1 5  chloride  65  M  =  SnBu  66  M  =  Li  3  10  four-membered  route  M  compound  (Scheme (prepared  ring  10). from  analogue 65,  from  ^-acylvinyl the  Low-temperature  known addition  tri-/7-butylstannyllithium  T h i s r o u t e is an e x c e p t i o n t o m e t h o d s b y w h i c h all the other c y c l i c j S - a c y l v i n y l a n i o n s y n t h o n s [19a, 2 0 a - b , 21b] are s y n t h e s i z e d , v i a M e t h o d B, all o f w h i c h h a v e u s e d m e t h o d o l o g y d e v e l o p e d in t h i s l a b o r a t o r y [7, 2 1 a ] . F o r previous use of similar methodology for alkylative 1,3-carbonyl transposition, see r e f e r e n c e s 3 a a n d 10. 15  20  [36] in  and magnesium 68% yield.  carbonate  compound  Elimination  in  cyclobutenyl  chloride  at  was  dimethylsulfoxide tin  compound  65 w a s found  the  ^-acylvinyl  the  cytotoxic  anion  (d  65  to 3  -70°C)  accomplished at  100°C  in  96% yield  be a  synthon)  germacranolide  followed  for  suitable 5, as  by  with 1  excess h  and  (Scheme  precursor  of  demonstrated  eucannabinolide  70  mesylation  in situ  powdered led  10). a  in the total  [21c].  69acis 69b trans  Scheme  21  11  As  synthetic  Li  70  to  gave  64  potassium the  desired  expected,  this  equivalent  of  synthesis  of  Coupling 65,  1.0  of  equiv.  addition  of  of  69.  of  methanol  ring  high  chairlike Kinetic  was  then  Although preceeding  no  synthetically  For use of  cyclic  the  67  from  variety  isomer  of  chemistry illustrated of a  the  of  ^-acylvinyl  anion  compound  single (85%  65  of  to  66  the added  rearrangement 68, resulting yielded  in  a  1:1  w a s stirred of  in  isomers  The intermediate  /9-acylvinyl  unknown  anion  69a  70.  was  reported,  t i n reagent  vinyllithium  the  65 as a  species  66,  5.  equivalent  5  macrocycles, see Scheme  22  cis-69a.  and  yield  led  15:1 r a t i o  eucannabinolide  the  and  the mixture a  of  equivalents  conditions  when  the masked  hitherto  85°C  carbonate,  product  five  intermediate of  w a s the desired  the natural  /?-acylvinyl of  potassium  82%  cyclobutenyllithium  the  [30]  11), w a s a  in  using  min)  and the O x y - C o p e  69a and 69b. However,  source  for synthesis  in  under  into  equivalent  at  substituent  30  chromatography  expected,  6 5 (1.3 e q u i v .  (Scheme  dimethoxyethane As  powdered  68  by  protonation  detailed  viable  in  of  -70°C,  w a s effected  state  transformations  and  flash  transition  The major  transformed  67. The adduct  expansion  isoprenyl  v i a lithiation  tetrahydrofuran,  by  yield".  containing  produced.  expansion  isolated  diastereomers,  was  16  in  via a  adduct  novel  was  the bulky  proceeded  dry  69  in  the enone  hexamethyldisilazide  formation  mixture  of  Oxy-Cope  potassium  the  /7-butyllithium  and  conversion).  to  of  and 67 w a s accomplished  1.0 e q u i v .  diastereomer  trans  66  to effect 8  (cf.  the o x y - C o p e  reference 20c).  ring  a  DISCUSSION  2.1  Preparation  Earlier as  reacting  in  our  synthetic  thesis).  converted  3-trimethylstannvl-2-cvclopenten-1-one  work  excellent  this  of  It  equivalents  w a s found  efficiently with  various  83% in  example,  the cuprate  min)  afforded yield  excellent  problem  One of  recent  [29],  reaction  reagent  of  laboratories  corresponding of  8  of  yields  (Table  amounts  of  later  I). H o w e v e r ,  insights  of  into  these  compounds  could  be  like  [39] ( e q u a t i o n  derivatives  lithium reagent  reagents  also  our attempts  by  contributions  of  ligands  performing  75 with  15 m i n ; r o o m  gave  these  of  organocopper  reagents  or m o d i f i e d  in a  1,4 s e n s e  the reagent  nature,  73  [38]  1.1  and  equivalents  temperature, ketone  reactions  to  at  14 gave this  lower  organic  reagents ketones  in  product  [38]. A l t h o u g h  chemistry  30  14  up the reaction  Gilman  a,/9-unsaturated  s e e reference 37.  23  by  (phenylthioXtri-  the desired  to scale  Gilman  to  72  10) [41].  3,3-bis(trimethylstannyl)cyclopentanone  the fundamental  a variety  in  ^-trimethylstannyl-a.^-unsaturated  cuprate  serve  earlier  /3-trialkylstannyl  (-20°C,  71  (summarized  trimethylstannylcopper 74  enones  3  3-iodo-2-cyclopenten-1-one  circumvented  is the ability  that  1  the  the £-iodo  cations  organocuprates ,  in t e t r a h y d r o f u r a n  12). O t h e r  that  /9-acylvinyl  our  the corresponding  was  synthesis deliver  types 8  (equation  unacceptable  1  the  had found  (cyanoXtrimethylstannyl)cuprate  For of  in  into  methylstannyl)cuprate lithium  laboratory  14  to [40]. F o r  temperatures exploring  and with  other  methods  extended  reaction  to effect  times  (vide  the desired  w e were  interested  in  transformation.  Me,Sn(PhS)CuLi  8  Me SnCu.SMe .LiBr 3  infra),  2  Me SnCu(CN)Li  73  74  3  (MejSn)(L)CuL.i  >  \  75 Table  I:  Reaction  11  14 of  the  ,9-iodo-a,/?-unsaturated  ketone  75  with  cuprates.  Cuprate  Reaction  8  -20°C, room  73  15 m i n ;  temperature  -48°C, room  74  condition  -48°C,  83  1 h;  min  24  80  1 h  90 m i n ; -20°C, 90  Yield  30 m i n  2 h; -20°C, temperature  %  82  organotin  During order  the  course  of  organocuprates  Q,^-unsaturated  our  of  work,  general  ketones  at  products  apparently  did  require  the  and  perhaps  lithium  bromide  [44],  [42a]. use  [45],  stabilizing  purposes,  isolation  solublizing  procedures  these  reagents,  is  readily  a  transferable  in  "dummy"  and  organocuprates second  the  To desired  group  use  the  ligand  was  this  high  new  goals  had  to  Reagent  of  the  inherent  of  copper  also  to  methyl), (thereby  3  of be  iodo  2  the  enone  benefits which  that  77  of  these  the  reagents  d i m e t h y l s u l f ide derivatives  reaction,  cyanide,  (stability already  [42]  the  towards 2  more  tendancy  saving  methodology  cuprous  with  (e.g.  [47])  for  workup  used  and  [43],  to  prepare  expense  possesses  and  [48]),  a  non-  higher  order  copper.  R,R Cu(CN)Li  =  overall  higher  rapidly  tri-/?-butylphosphine  the  (I)  reported  2  as  that  yields  phosphorous  [46],  hence,  high  standpoint,  such  commonly,  Moreover,  attached  form  transformation  following  (a)  of  other  source  coworkers  "dummy"  methyl  to  ligand  additives  and,  react  provide  practical  triethylphosphite  simplified.  addition  available  Lipshutz  a  were  of  to  reported  76  2  a  more  hexamethylphosphoramide or  From  co-workers  R Cu(CN)Li2  temperatures  addition  2  and  forumla  low  conjugated  not  Lipshutz  into  highly  (Rj= to  a  our the  transferable  transfer  valuable  mixed  Rj  in  ligand,  preference  R  2  = to  R,).  endeavour,  i.e.  trimethylstannyl  to  effect  enone  72,  the the  achieved.  form  (Me SnXMe)Cu(CN)Lij 3  78  had  to  be  prepared.  The presence of boron trifluoride-etherate w a s s h o w n to enhance reaction rates a n d / o r p r o d u c t y i e l d r e l a t i v e t o t h o s e o b s e r v e d in the a b s e n c e o f t h i s L e w i s acid [42c]. 2  Preferential release of one group f r o m a copper center relies on several f a c t o r s [42, 5 0 ] , s u c h as a g g r e g a t i o n s t a t e , extent of b a c k b o n d i n g b e t w e e n a ligand and c o p p e r , and s t a b i l i t y o f b o t h 7 7 and the l o w e r order cuprate resulting f r o m the l o s s o f Rj in 7 7 . 3  25  (b)  More  conjugate  sense  synthetically  2.1.1  impotantly,  74  reagent  of  t o deliver  with  0-iodo  the trimethylstannyl  enones  in a  group  selectively in  to a  cold  yields.  o n e equivalent  of  of trimethylstannyllithium  resulted  h a d t o react  of the higher order cyanocuprate 7 8  Preparation  solution min)  a n d b e able  useful  Addition  this  in a bright  orange  solid  cuprous  in tetrahvdrofuran  solution  cyanide 4  o f lithium  (-78°C,  5  (-78°C)  m i n ; -48°C,  15  (cyano)(trimethylstannyl)cuprate  [49] ( e q u a t i o n 12). Me SnLi 3  Subsequent afforded  a  +  CuCN  addition  Me SnCu(CN)Li  74  3  o f o n e equivalent  homogeneous  tan solution  Me SnCu(CN)Li  +  of  of  methyllithium  t h e higher  (12)  at - 2 0 ° C  order  (5  min)  cyanocuprate  78  (equation 13). 3  We  were  cyanocuprate equivalents  pleased  7 8 can be prepared of methyllithium  tetrahydrofuran -20°C,  also  MeLi  with  5  to  find  that,  in a o n e - p o t  t o a slurry  o n e equivalent  15 m i n ) t o g i v e  M e ^ M e j C u f C N p j  immediately  alternatively, reaction  of  hexamethylditin  a bright  yellow  the  b y direct  o f o n e equivalent  (13)  higher  addition  order of two  o f cuprous  cyanide in  at  (-78° C  slurry , 6  78  -78° C  which  turned  to  into  a  T h i s reagent c a n a l s o b e prepared i n diethyl ether. H o w e v e r , f o r these reagents tetrahydrofuran i s t h epreferred solvent since m o r e highly m i x e d cuprates like Me(/7-Bu)Cu(CN)Li in diethyl ether r e v e a l e d free m e t h y l l i t h i u m at l o w t e m p e r a t u r e s , along with i t s lower order counterpart MeCu(CN)Li [57-59]. 4  2  These reagents have markedly different reactivity depending o n whether these r e a g e n t s a r e p r e p a r e d i n t e t r a h y d r o f u r a n o r d i e t h y l e t h e r [ 4 2 b ] (vide infra). 5  This o c c u r e d w h e n a p p r o x i m a t e l y half t h e v o l u m e o f methyllithium w a s added (=1 e q u i v . ) t o t h e r e a c t i o n m i x t u r e . T h i s c o u l d h a v e b e e n d u e t o t h e f o r m a t i o n of 7 4 . This s u s p i c i o n w a s later c o n f i r m e d t o b e true. Thus, the l o w e r order cuprate 7 4 f o r m e d v i athis method reacted with 3-iodo-2-cyclopenten-1-one (-48°C, 9 0 m i n , - 2 0 ° C , 9 0 m i n ) t o give 7 9 % o f t h e corresponding t i n enone 14 as t h e o n l y p r o d u c t . There w a s n o i n d i c a t i o n (glc a n a l y s i s ) , that m e t h y l t r a n s f e r 1  26  homogeneous  2.1.2  t a nsolution  soon  Reaction of the higher  We  were  90 83%  extremely  reagent  min) afforded yield  earlier  None showed  pleased  to  with  1.2  in tetrahvdrofuran  14). T h i s  yield  find  that  equivalents  (-78°C,  enone 75  the of  reaction  the  90 m i n ; -48°C,  higher  order  60 min;  3-trimethylstannyl-2-cyclopenten-1-one compared  well  with  those  of  0°C,  14 i n  obtained  in  the  I).  o f themethyl  the presence  reported  75  the corresponding  (Table  hexamethylditin).  transfer of  The spectral  only  product  could  be detected  o n e component  properties  o f this  beside  material  (tic a n d a  were  small  glc analyses amount  identical with  of  those  earlier [38].  The strong  78  (equation  studies  7  order cyanocuprate 78 with the fi-iodo  3-iodo-2-cyclopenten-1-one cyanocuprate  thereafter .  structure  absorption  o f t h e t i n enone band  at  w a s confirmed  14  1685 cnrr  1  in  t h e ir  b y its spectral  spectrum  of  this  data.  A  compound  '(cont'd) had occurred. Formation o f this " o n e - p o t t i n cuprates" b y addition o f 1 equiv. o f m e t h y l l i t h i u m in ether t o a c o l d (usually - 7 8 ° C ) tetrahydrofuran solution o f 1 e q u i v . o f h e x a m e t h y l d i t i n a n d 1 e q u i v . o f c o p p e r (I) s o u r c e (phenylthiocopper or cuprous cyanide) gave reagents which behaved exactly the same as the c u p r a t e s 8, o r 74 r e s p e c t i v e l y . T h i s m e t h o d w a s e m p l o y e d f o r l a r g e s c a l e (using p h e n y l t h i o c u p r a t e 8) p r e p a r a t i o n o f t h e t i n e n o n e 14. From practical stand convenient. 7  point  thesecond  method  27  w a s found  to be more  indicated showed  the a  presence  strong  trimethylstannyl nine-proton  of  an  absorption  group  singlet  o./J-unsaturated  band  [52]. T h e  at  6  at  'H  762  nmr  0.25 ( with  ketone.  c m  -  1  spectrum  satellite  peaks  which of  The  ir  was  attributed  this  spectrum  material  also  to  the  exhibited  due to tin coupling,  a =  u  on-n 56  Hz) which  of  this  w a s attributed  compound  satellite  peaks,  Reaction higher with  order similar  room  gave  J  c  =  w  of  cyanocuprate reaction  temperature  with  medium,  although  a  methyl  is  required  protons'.  triplet  (J  =  2.3 H z ) at  7 8 (prepared  min)  75  in diethyl  in diethyl afforded  ether the  with  ether  1.2  6  proton  6.37 (with  consumption  of  starting  (-78°C,  90  can also  occur  9  group 10  [42b].  the trimethylstannyl  is  This  transferred  Although higher  of  the  tetrahydrofuran, 90 m i n ,  3-trimethylstannyl7 9 in a ratio  indicated  that  4.5 : 1 in  preferentially,  further  order  of  min; -20°C,  corresponding  material.  equivalents  instead  14 and 3 - m e t h y l - 2 - c y c l o p e n t e n - 1 - o n e  establish  The olefinic  33 Hz).  the trimethylstannyl  group to  methyl  to a one-proton  conditions) 15  complete  of  the stannyl  3-iodo-2-cyclopenten-1-one  -2-cyclopenten-1-one (glc)  rise  to  study  cuprate  78  ether  transfer  in this  area  as a  viable  The proton chemical shifts of the trimethylstannyl compounds are relative to CHCIj. There are three naturallly o c c u r i n g tin i s o t o p e s w h i c h have magnetic moments (I = 1 / 2 ) : Sn, S n , and S n . D u e t o their higher relative abundance, S n (7.67%) a n d S n (8.68%) a r e t h e i m p o r t a n t o n e s . A s a g e n e r a l rule o f t h e indirect tin proton couplings J ( S n - C - H ) and J ( S n - C - C - H ) are a l w a y s slightly l a r g e r (=5%) f o r S n than f o r ' S n [53]. Throughout this thesis the magnitude of these coupling constants are given as J ( S n - H ) / J ( Sn-H) where the coupling constants f o r the t w o i s o t o p e s are distinct and as an average o f the t w o values where they are not distinct. 8  U 5  n 7  n 7  n 9  1 1 9  1 1 9  l l  n 7  T h e 1,4 a d d i t i o n s p e r f o r m e d in tetrahydrofuran s l u g g i s h [ 5 4 - 5 5 ] . T h e d i f f e r e n c e s in a g g r e g a t i o n solvent, might be responsible f o r this behaviour 9  1 1 9  as solvent are notoriously state of 7 8 , a function o f [50, 56, 57].  Reaction of 3 - i o d o - 2 - c y c l o h e x e n - 1 - o n e 7 w i t h 1.2 e q u i v a l e n t s o f t h e h i g h e r order c y a n o c u p r a t e in diethyl ether (-20°C, 30 m i n ) gave 3-trimethylstannyl-2-cyclohexen-1-one 9 and 3-methyl-2-cyclohexen-1-one 8 0 in a r a t i o o f 15.7:1 w i t h c o m p l e t e c o n s u m p t i o n o f 7 , w h e r e a s r e a c t i o n in tetrahydrofuran (-20°C, 45 m i n ) g a v e t h e p r o d u c t 9 a n d s t a r t i n g m a t e r i a l in t h e r a t i o 3.4:1 (These r e s u l t s c o n f i r m t h e f a c t that t h e higher o r d e r c y a n o c u p r a t e i s l e s s r e a c t i v e but m o r e s e l e c t i v e in tetrahydrofuran). 1 0  28  reagent it  for transfering  can transfer  this  a trimethylstannyl group  group, w e were  selectively  and  it  could  pleased  be  used  to discover to  that  alleviate  our  problems.  All out  large  by  methods  reaction 3  h)  scale  described  conditions.  there  preparations  Thus,  14  [21b].  2.2  Preparation  of  the /0-trimethylstannyl  elsewhere  using  w a s obtained  of  an 8 2 % isolated  the early  to obtain  since  the reagent  [21b]  and since  importance  in  to  modifications  to the  in tetrahydrofuran  8  of  carried  of  of  M  =  SnMe,  21  M  =  Li  our  the ^-trimethylstannyl  d  3  synthon  corresponding  synthon.  3  (equation  t o this  studies  simple  to  synthon  [60]. M o r e o v e r ,  effect.  More  we  blackening  of  A n y attempt the  solution  to  importantly,  raise  and  29  route  derivatives from  a  14  the temperature  led to  partial  =  H  E  =  SnMe  two B,  3  different Scheme  w a s attractive  to us  synthesized  before  had recently  gained  practical  our  P  w a s (Path  had not been  3-trimethylstannyl-2-cyclopenten-1-one  [32] f a i l e d .  considered  Our choice  15). T h i s  3-substituted-2-cyclopenten-1-ol  synthetic  enone  81  81  investigations, d  (-78°C.  OP  20  the cyclopentenone  seemed  acetalization  led  stages  v i a the c y c l o p e n t e n o l  procedure  yield  were  14  OP  During  pathway  slight  3-trimethylstannvl-2-cyclopenten-1-ol  14  5)  with  the phenylthiocuprate  O  routes  [39], or  enone  standpoint,  efforts  to  at - 7 8 ° C  effect  this the  via  Noyori's  (for example  -20°C)  recovery  of  the  starting  material  at  the  end  of  the  experiment.  4 OH  DIBAH  SnMe  3  14 Reaction of  3-trimethylstannyl-2-cyclopenten-1-one  diisobutylaluminium  hydride  pIBAH)  3-trimethylstannyl-2-cyclopenten-1-ol of  band  at  3290  spectrum  also  presence  of  'H  nmr  this  material  crrr  of  this  peaks  stannyl  methyl  singlet  at  6  rise  to  a  one-proton  H  =  35/39  peaks, i  S  n  _  to  protons. 1.48  the  and  a  tin  (exchanges  broad  by  its  presence  of  at  J g  n  a =  H  of  the  D,0).  a  doublet  nine-proton Hz)  =  A  2  16)  yielded  [61].  767  cm-  group  gave  at  6  The  at  6  0.16  attributed rise  of 5.94  ir  indicating  1  the  respectively.  singlet  proton  The  absorption  functionality.  was  Hz)  h)  broad  which  olefinic  equivalents  1.75  functionality,  hydroxy  (J  data.  and  1  1.2  (equation  hydroxy  crrr  55  The  (0°C,  yield  spectral  1690  exhibited  proton with  98%  with  14  hexane  trimethylstannyl  coupling,  The  dry  in  81  bands  material  satellite  gave  due  bond  in  1 1  confirmed  absorption  double  spectrum  was  indicated  1  showed  a  SnMe,  81  of  structure  (16)  to  this  The (with  to a  the broad  compound  (with  satellite  Hz).  Okamura and c o - w o r k e r s have used s o d i u m borohydride to effect a similar t r a n s f o r m a t i o n (vide supra) [ 1 9 a ] . W h i l e L u c h e ' s p r o c e d u r e g i v e s e x c e l l e n t y i e l d s [ 6 2 ] , f o r r e d u c t i o n o f c o n j u g a t e d e n o n e s , D I B A H [61] i s c o n s i d e r e d t o b e t h e reagent of choice. B e s i d e s , sodium borohydride w a s s h o w n to yield saturated a l c o h o l s as w e l l as M i c h a e l a d d i t i o n p r o d u c t s in a d d i t i o n t o the d e s i r e d 11  unsaturated  alcohol, see  M.R.  Johnson,  and  (1970).  30  B.  R i c k b o r n , J.  Org.  Chem.,  35,  1041  2.3  Preparation  Silyl  ether  volatility  derivatives  o f trimethylsilyl  separation mass  of 3-teAr-butvldimethylsiloxv-1-trimethvlstannvlcvclopentene  and  structure  spectrometry.  derivatives  limits  group.  Their  reagents) at  because [33],  which  them  is, therefore, specific  this  protecting  and  hand,  t o steric  removal  was  of 3-trimethylstannyl-2-cyclopenten-1-ol chloride  dimethylformamide  (room  i n the  presence  temperature,  butyldimethylsiloxy-1-trimethylstannylcyclopentene  range  of  of  with  [67].  and these  31  of  hydroxyl  alkyllithium attack  More  importantly,  [33]  o r aqueous  ion  endeavour . 1 2  81 with  1.1 e q u i v a l e n t s o f  min)  gave  8 3 (equation  o f imidazole 97%  of  17).  R e c e n t l y , a direct c o n v e r s i o n o f feAf-butyldimethylsilyl ethers into c a r b o n y l c o m p o u n d s w i t h J o n e s reagent i n the p r e s e n c e o f p o t a s s i u m f l u o r i d e has b e e n e f f e c t e d . S e e , H . - J . L i u , a n d l . - S . H a n , Synth. Commun., 1 5 , 7 5 9 ( 1 9 8 5 ) 12  for  reaction  b y nucleophilic  o f 5 equivalents 90  suited  f o r the  treatment  fluoride  The  T h e stability  groups  proceed  t o our  them  hydrolysis  wide  hindrance  properties.  chromatography  [65],  (e.g.  b y either  attractive  of  protecting  reactions  make  o f gas  to a  conditions  these  sensitive mild  ethers  groups  derivatives  basic  o f useful  t h e ease  effective  that  group  [64]  b y a combination  6 6 ] ether  fact  a number  a s protecting  t o strongly the  have  dimethylsilyl  particularly  from  feAf-butyldimethylsilyl dry  utility  [33,  o f its  Reaction  and  elucidation  their  stability  results  silicon,  acid  make  [63]  O n t h e other  ferr-butyldimethylsilyl conditions,  o f alcohols  83  in 3-tert-  The  structure  spectrum  showed  presence  of  of  isolated group  singlet  (6  to  tert-buty\  the  appeared satellite  0.097)  at  6  to  due  1090  double  bond,  an  to  silyl  The  at  coupling,  J -  =  (C-0  while  6  0.93.  36/40  spectral c m  Hz)  The  Hz)  was  at  the  and  a  the  six-proton singlet  trimethylstannyl 2  ir  indicating  nine-proton  The =  ,  1  exhibited  a  (J  -  data.  stretching)  spectrum  doublet  ,,  its  778  ether  groups,  broad  by  and  nmr  appeared  one-proton tin  *H  methyl  groups  A  confirmed  1583,  the  methyl  was  at  respectively.  due  0.15.  peaks  compound  absorptions  an  trimethylstannyl  this  6  methyls  5.82  attributed  to  due  (with  the  C-2  on—n olefinic  proton.  The were  broad  attributed  36.90  and  143.95  2.4  MH  the  148.22).  with  Gilman reaction  of  The  and  These  of  (sp ) two  data  nmr  showed  carbons  3  other  were  confirmed  (6  nine  -10.83.  attributed the  signals.  to  -5.10, the  sp  Seven  17.98,  of  them  25.67,  34.09,  carbon  5  centers  (8  and  its  structure.  l-lithio-3-ferr-butvldimethvlsiloxycyclopentene  co-workers  tetraphenyltin  tool  in  to  organic  84  published  by  of  the  +  4  (CH,=CH) Sn 4  excess  as  of  that  tetra-n-butyltin  /7-butyllithium  transmetalation  this  reaction  preparation  phenyllithium  Ph«Sn  showed  [30],  can  be  prepared  (equation  18).  has  developed  been  This  by  process, into  a  synthesis.  utility  co-workers  [68]  with  referred  synthetic  reaction  the  "C  electrophiles  commonly  valuable  decoupled  saturated  and  Preparation  reaction  now  to  79.45)  and  band  with  of  4  demonstrated  vinyllithium,  tetravinyltin  /?-BuLi +  was  > PhLi  32  (equation  /j-Bu Sn  +  4  *  a  4  CH  J =  when  reagent 19) 4  CHLi  Seyferth  hitherto  and  unknown,  [69].  PhLi +  ^ ) 1 8  Ph Sn 4  ( i g  ^  Bu,Sn /7-BuSnH H C H B C — C H , — O T H P  AIBN,  THP  Z\  85  86  n - B u L i , THF -78° C  Li n-Pr—CBEC—Cu OTHP  <<  Scheme  88  Corey  and  functionalized showed  that  [70],  in  one  vinylstannane  as  a  precursor  hydrostannation n-butyllithium species cuprate  87.  of at  (scheme  13).  hydrostannation.  of  acetylene  terminal  temperature of  for  the  the  the group  approach  Thus,  earliest  the  Conversion  similar  the  vinylstannane  (E)-3-hydroxypropenyl  A  of  functionalized  low  allowed  87  12  Wollenberg  the  - O T H P  Cyclohexenone  (-78°C)  to  an  has  acetylene  Transmetalation  85.  lithio  used  89  was  of  90  in  converted yielded  33  use  anion  be  of  a  synthon,  prepared  via  of  86  with  in  formation  of  the  lithio  into  corresponding  the  ketone  a  the  Transmetalation  addition  a.^-unsaturated  been  could  species  conjugate  of  0-acylvinyl  86  resulted  resulting ready  a  reports  the of  (scheme  prostaglandin into the  the  the  protected  12).  synthesis  vinylstannane  corresponding  [30b] 90  via  /9-acylvinyl  BUjSn  V  /7-BuSnH H C = C — C H — n - C I OSiEt,  3  H  n  OSiEt,  90  89  n-BuLi  11  92  Scheme  anion  reagent  functionalized and  reagents  (a)  Formation  literature accessible  become  of  cyclopentenone  (±)-15-epiprostaglandin  The  has  91.  popular  the reaction  records  the  cuprate  usually  reagent,  92, and hydrolysis, E  3  reaction  afforded  with  the  highly  (±^prostaglandin  E  2  93  94.  an extensive  via transmetalation among  13  synthetic  proceeds  survey of  organic  smoothly  34  of  recent  vinylstannanes chemists at  examples  of  vinyllithium  [71, 30]. This  process  for the following  reasons:  l o w temperatures,  (b) t h e  reaction  is  completely  stereospecific,  coordinatively of  saturated  the vinyllithium  With  our  and  (c)  tetraalkyltin  the  which  does  preparation  was  to  that  the transmetalation  when  a  of  the  the transmetalation of  tetrahydrofuran  methyllithium  at - 7 8 ° C  reagents  for  0-acylvinyl  results  A of  83  argon, the  produce  84 the  are summarized  typical (0.27  w a s added  resultant  pale  this  proceeded of  the  interfere  reacted  in  reaction  with  the  yellow  dropwise yellow  a  accomplished, We  is  a  reactions  were  with  solution  of  (3-ferf-butyldi-  the  task  pleased  and cleanly  treated  (equation  smoothly  at  1.2  at to  -78°C.  equivalents  hand find Thus, of  1—Iithio-3—rerf-butyldi-  20).  with  substituted  a  variety  allyl  of  electrophilic  ethers.  Some  (-78°C),  stirred  of  the  II.  is a s f o l l o w s mL  precursor  substance.  was  corresponding  3  anion  smoothly  83  1 h, a pale  in Table  procedure mmol)  of  83)  84 w a s obtained  intermediate to  83  solution  methylsiloxycyclopentene  The  not  of  species.  methylsiloxy-1-trimethylstannylcyclopentene study  by-product  of  dry  solution  solution  [35]. T o  a  cold  tetrahydrofuran, of  methyllithium  w a s stirred  35  at  -78°C  under  an  in ether for  solution  atmosphere  of  (0.32 m m o l ) a n d  1 h.  Cyclohexanone  Table  II:  Reaction  of  1-lithio-3-te/?-butyldimethylsiloxycyclopentene  84  with  electrophiles.  OSifMejJBu  OSiCMe^i/  1  \—'I  E 95  84  Entry  Electrophile  (E )  Product  +  E  in  95  %  Yield  1  CH (CH ) I  96  CH (CH )-  60  2  R(CH ) Br  97  R(CH ) -  72  3  cyclohexanone  98  1-hydroxy-  78  3  2  2  3  2  J  3  2  2  2  1  cyclohexyl 4  cyclopentanone  99  1-hydroxy-  77  cyclopentyl 5  RCH -CH0 2  1  Yield  of  2  R  2-cyclopentenyl  =  (0.35  mmol)  stirred aqueous to  distilled  room  sodium  for  was an  sodium  purified  added  additional  bicarbonate  The and  RCH CH(OH)-  61  2  product  (in  1  mL  period  bicarbonate  temperature.  100  2  and  ether dried  of  tetrahydrofuran) 1  diethyl solution  over  h.  After ether, was  anhydrous  36  and  the  reaction  mixture  successive  addition  of  the  mixture  was  allowed  then  washed  with  saturated  magnesium  sulfate.  was  saturated to  warm aqueous  Evaporation  of  solvent, of  followed  pure  by  distillation  of  compound  98 w a s confirmed  exhibited  attributed  to  attributed  C - 2 olefinic  to  the  indicated  the presence  of  of  weak of  the  other  doublet  broad  o i l gave  52  m g (78%)  a double  (J  =  bond.  at  There  listed Each (high  intermediate reagents.  in Table of  these  gave  resolution  mass  6  at  methylene  also  6  in  1  The  of  this  5.55 which w a s 1.27-2.71 w a s  protons  appeared  the  and  ir  a broad  the  spectrum absorption  function.  was  results  also  allowed  are  spectral  products  signal  1618 crrr  84  The  II  2 H z ) at  unresolved  band  98.  T h e 'H n m r s p e c t r u m  cyclopentenyl  absorption  electrophilic  determination  A  and  vinyllithium  structures.  broad  data.  w a s due to the hydroxyl  1  the products  assigned weight  The  c m ' which  Similarly,  All  the residual  its spectral  proton.  cyclohexyl  proton.  at 3360  by  a one-proton  hydroxyl  variety  of  1-(1-hydroxycyclohexyl)-3-terr-butyldimethylsiloxycyclopentene  structure  band  (air-bath)  to  react  summarized  data  gave  in full a  in  with Table  accord  satisfactory  a II.  with the molecular  spectrometry).  98 In  connection  should  be  carbonyl h),  the  -78°C showed  with  noted.  Although,  compounds alkylation  and 1 h that  the  (entries  reactions  at r o o m  essentially  data the  summarized reaction  3 - 5 , Table (entries  temperature. only  of  in the  Table  II)  Glc analysis  one product,  37  the  vinyllithium  II) p r o c e e d e d  1-2, Table  II,  to  were of  contaminated  following reagent  completion carried  the crude with  out  84  with  at - 7 8 ° C for  reaction  small  points  amount  1  h  (1 at  products of the  protonated could  be  species, purified  tetramethyltin  was  by  could  obtained  a  simple  be  from  each  distillation  separated  very  reaction.  (air-bath),  easily  from  In  since the  general the  various  the  products  relatively  volatile  reaction  products  95.  2.5  Conjugate  addition  of  cuprate  and  Grignard  l-lithio-3-terf-butvldimethylsiloxvcvclopentene  Organocopper organic ability  reagents  synthesis. to  below  form  room  The  have  played  usefulness  carbon-carbon temperature)  of  under  After  be  the  generated  conjugate  important from  addition  task  and,  84, to  at  hand if  enones  was  so,  and  to  relatively  mild  rather  than  valuable proper  tend  vinyllithium  to  excellent  at  generate  bis-homocuprates  auxiliary  reactions  to  low  couple  reagent  ligand  102, in  so  as  temperatures [73]).  Both  non-transferable  the to (at  the  as  the  history  attributed  conditons  whether  the  such  reagents  cuprate are  their  (e.g.,  at  viability  equivalent  explore  to  of  of  viable  of  a  species  or  d  3  could  to  effect  102  2  desirable  be  recent  101  R CuLi  was  from  enones.  R(L)CuLi  It  the  demonstrated  84  whether  /9-iodo  in  can  l-lithio-3-rerf-butyldimethylsiloxycyclopentene synthon,  role  reagents  having  derived  enones  pivotal  these  bonds  [72].  a  to  84  species  heterocuprates in  order  process. enable higher  phenylthio  ligands.  38  of  to  It us  save  was to  the  general one  equally  temperatures and  the  structure  equivalent  important  perform  to  of select  101 the a  conjugate  addition  these .vinyllithium  reagents  cyano  groups  proved  to  be  Addition  of  solid  phenylthiocopper  (1  equiv.)  1-lithio-3-terf-butyldimethylsiloxycyclopentene yellow the  slurry  w a s stirred  phenylthiocuprate  cuprous The  cyanide  pale  afford  yellow  by  for  to  thus  solution  addition  -78°C  equiv)  slurry  of  at - 7 8 ° C  a  1 equiv.  of  white  to  of  yielded  a  solution  of  a yellow  of  in  84  stir  Grignard  of  to  by  adding  tetrahydrofuran.  at - 7 8 ° C  bromide  solution  solution  w a s prepared  104  corresponding  dry magnesium  the desired  (-78°C)  tetrahydrofuran  solution  w a s allowed  The  104.  cold  for 1 h to afford  (-78°C)  produced  of  1 h to yield  cold  a  in  84  Similarly, the cyanocuprate  103.  (1  yellow  a  made at  which  to  for  reagent  1 h to  the solution (equation  105  was  105  of  84  21).  t  t  (21)  84  Importantly, reaction  with  conjugate  reagents  enones,  addition  103,  to  afford  products.  with  -48°C, these 107  3  tetrahydrofuran h)  to  produce  transformations could  appropriate  be  enone  in  bromide-dimethylsulfide  and  to  were  by the  = =  [CuSPh]Li [CuCN]Li  105  X  =  MgBr  yields  of  2-cyclopenten-1-one,  of  in  (-78°C,  103  products  the Table  reaction  of  presence  the of  complex.  39  III.  3 106  -  to allow for  the  corresponding  were  or  Similarly,  Grignard  0.5  h)  stable  2-cyclohexen-1-one,  3-iodo-2-cyclohexen-1-one  solutions  listed  X X  sufficiently  excellent  the corresponding  are  produced  good  Specifically,  3-iodo-2-cyclopenten-1-one react  a n d 105  104  103 104  (-78°C,  104  109.  allowed 1  The results  compounds  reagent  equivalents  to  105 of  h; of  106  and  with  the  copper  (I)  A (0.2  typical  mmol)  added the  in  procedure  is as f o l l o w s .  3  dry tetrahydrofuran,  mL  of  phenylthiocopper  resultant  (0.27 m m o l )  yellow  slurry  3-iodo-2-cyclopenten-1-one slowly After  added  mixture was of  addition  w a s allowed  filtered  through  petroleum  the  solvent  the  residue  distillation  to a  ether.  of  yellow  warm  to  column  silica  (air-bath)  under  gel  of  (8  the  at  -78°C  for of  of 1  pressure.  elution  thus  with  A  afforded  at  3  -78°C  ether  structure  spectrum 6  of  this  6.19 w h i c h  singlet  at  system.  8  The  cyclopentenyl 1707  cm-  system. two  1  confirmed  exhibited  w a s attributed  series and  in  the  multiplets  ir  spectrum  absorption present  the  cuprate  The other  T h e data  to  cyclopentenone  bonds  systems.  of  a  by  the  olefinic  from  6  indicated at  the  spectral  of  1.75-2.88  of  The of  1624 and 1640 c m  50 m L  sulfate  data.  -  1  of  3:1) and  =  H  J  2  ether.  pure  nmr  H z ) at  T h e other  cyclopentenone  attributed  strong  to  the  absorption  unsaturated were  and  [76]  The  (J  the  was  presence  with  (74%) o f  doublet  proton  slurry  108.  the allylic  protons.  yellow  55.4 m g  h.  (15 m L ) , t h e  ether-ether,  broad  proton  methylene  bands  its  one-proton  to the olefinic  5.99 w a s attributed  Similarly,  enones.  was  108  compound  The weak  double  enone  of  for  chromatography  3-(3-ferr-butyldimethylsiloxycyclopent-1-enyl)-2-cyclopenten-1-one  The  of was  magnesium  Flash  tube) and  solution  w a s eluted  over  84  argon, w a s  bent  The resulting  petroleum  obtained  a  of  tetrahydrofuran  w a s stirred  w a s dried  of  h.  dry  and the column  eluate  g,  mL  temperature.  reduced  oil  rotation  »1  solution  atmosphere  (0.5 m L ) a n d p e t r o l e u m  Florisil  The combined  an  stirred  (by  in  room  of  under  solution  methanol  (-78°C),  solid  stirred  (0.33 m m o l )  w a s removed on  as a  was  and the resultant  successive  To a cold  at  carbonyl  attributed  to the  in the molecule.  intermediate reagents  is s u m m a r i z e d  103  was  a n d 105  104  in Table  40  III.  allowed  were  A l l of  to  similarly  react  with  reacted  the products  cited  other  with the in  Table  108  III  gave  spectral  products mass  also  gave  a  in  full  accord  satisfactory  with  the  molecular  assigned  weight  structures.  determination  Each  of  (high  these  resolution  spectrometry).  In  all  cases  straightforward. (103,  104  process, of  data  109  the  (elution  The  and  105  involving reagents  essentially These  studied,  of  with  respectively)  103,  materials  reactions  phenylthiocuprate,  enones.  the  the  104  In and  conjugate  were  petroleum  easily  the  gave  each 105  quite  to  the  the  by  ether-ether).  41  yields  crude  enones,  product  separated  efficient  cyanocuprate  comparable  case,  addition  were  and column  and in  product including a  small  and  the the  experimentally  Grignard  reagent  conjugate  obtained  after  iodoenones, amount  chromatography  addition  of on  addition consisted  the  enone.  silica  gel  Table  III:  with  Reaction  enones  X X X  103 104 105  and  = = =  of  the  cuprates  0-iodo  103  and  104  and  the  Grignard  95  Electrophile(E')  Product  2-cyclopen-  106  E  in  95  Cu(CN)Li  Yield  3-oxocyclo-  65  pentyl  ten-1-one  69  2  91  Cu(SPh)Li 2-cyclohexen-  Cu(CN)Li  107  3-oxocyclo-  80  hexyl  1-one MgBr  %  72  Cu(SPh)Li  MgBr  105  enones.  [CuSPh]Li [CuCN]Li MgBr  X  reagent  85  2  3-iodo-2-  Cu(SPh)Li  108  3-oxocyclo-  74  pent-1-enyl  cyclopenten-1-one Cu(CN)Li  72  3  109  3-iodo-2-  Cu(SPh)Li  en-1-one  1  Isolated  2  Catalyzed  3  Via  yield by  "one-pot"  with  respect  CuBr.SMe cuprate  3-oxocyclohex-1-enyl  cyclohex-  to  the  enones  2  formation  42  89  1  Our the  success  hand  and made  when  solution  of  we  suspension  to  (-78°C,  in  104  cuprate"  formation  15  generalize  these  "one-pot"  of  led us  to  cyanide  which  (1  and 1 equiv.  of  the stannyl  30  m i n ) (equation  exactly  Hence  ,  m L ) (-78°C,  procedures  we could  were  fashion. cold  0.9 1  to  the  equiv.  3  further  find  to our  same  of  -48°C,  Although  pleased  be applied  h;  in  22).  that  h)  43  Success w a s  (-78°C) ether  A  pale  manner  was  research these  endeavours.  104  be  stirred 8 3 in yellow as the  3-iodo-2-cyclopent-  CN 83  whether  could  a  1 0 8 in 7 2 % y i e l d .  findings,  similar  83  to  behaved  earlier.  in a  explore  methyllithium  min; -20°C,  described  product  the cuprate  equiv.  cuprous  tetrahydrofuran  the desired  simple  of  form  1  w a s produced,  cyanocuprate en-1-one  to  added  1 equiv.  tetrahydrofuran  into  "one-pot  1-trimethylstannyl-3-fe/-f-butyldimethylsiloxycyclopentene  transmetalated at  at t h e  transformed is  required  practical  and  EXPERIMENTAL  3.1  General  information  Boiling refer  to  liquid  short  films  calibrated nuclear using or  Varian  magnet  of  the  a  and a  in  6  [74])  with  tin-proton  coupling  two  values  recorded  with  a  possible)  for  where  recorded  In  case  of  usually  made  two  are  with  a  compounds  (high  resolution  on the (M* -  alkyl)  the  are  indicated  as J  U 7  Low  50  trimethylstannyl spectrometry) [75].  44  Sn-H)/  In  or  while MS  groups were  groups  the  high  coupling  where  average  of  the the were  resolution  mass  spectrometer.  molecular on  The  spectra  mass  the  7.25  parentheses.  mass  based  (6  protons,  an  are case  u  902  A l l MH  the  J( 'Sn-H)  and as  were  positions  signal  in  resolution  spectrometer MS  of  solution  console.  chloroform  are  distinct  carbon-13  superconducting  TT-23  number  were  spectra  fe/-?-butyldimethylsilyl  are given  peak  MHz  63.4 K G  Bruker  multiplicity,  Kratos/AEI  mass  270  standard.  to  and  on  spectrometers  internal  mass  with  The  XL-100  (TMS) as  distinct.  CH4B  or  Signal  isotopes  obtained  and  otherwise.  assignments  not  a  Proton  stated  relative  The  and  to  and/or  J(Sn-H)  Varian/MAT  were  determinations  the  they  spectra the  unless  were  temperatures  deuterochloroform  Instruments  attached  determined  otherwise.  film.  spectrometers.  an Oxford  spectra  constants  constants  polystyrene  XA-100  of  air-bath  710B spectrophotometer  T-60, EM-360,  WH-400  as  (ir) s p e c t r a  run a s  tetramethylsilane  were  Infrared  were  trimethylstannyl  stated  (wherever  or  MHz  with  positions  of  16K c o m p u t e r  80  constants  coupling  models  comprised  were  unless  band  1  indicated  model  (nmr) spectra  WP-80  units,  distillations.  crrr  resonance  Nicolet  and those  Perkin-Elmer  1601  unit  compounds  resonance  a  Associates  spectra  given  using  models on  uncorrected  (Kugelrohr)  (neat)  magnetic  recorded  are  path  using  Bruker  nmr  points  1 2 0  Sn  and  weight were  Analytical  gas-liquid  Hewlett-Packard stainless  model  steel  column A)  chromatography  5832A  gas  packed  with  and a  chromatograph  (column  model  5880  gas chromatograph  using  coated  with  cross-linked SE-54  (column  plastic-backed  silica  aluminum-backed on  20 x  Gel  60).  gel  20  Flash Gel  Silica  (E.  column  was  or  0.21  with  mm  Florisil  of  on 230-400  a  0.125 in. Chromosorb  Hewlett-Packard silica  column  detector.  on  commercial  Type  13181)  or on  tic w a s accomplished  silica  g e l (E. M e r c k ,  on  70-230  Chemical  mesh  on  x  fused  Sheet  w a s done  (J.T. Baker  a  out  Preparative  0.7 m m  ft mesh  on  carried  5554).  6  ionization  Chromatogram  chromatography  [76] w a s d o n e  x  a  80-100  detector,  mm  performed  using  B) and a flame  Type  coated  G e l 60) or  chromatography  25  (Eastman  Merck,  plates  Conventional  silica  mesh  Co., 100-200  Silica silica mesh).  g e l (E. M e r c k ,  Silica  60).  Unless of  stated  dry argon  Cold aqueous C0  plates  a  (tic)  gel plates  c m glass  (E. M e r c k ,  conductivity  chromatography  was  3 - 5 % O V - 1 7 on  W(HP)  Thin-layer  thermal  (glc)  2  using  otherwise, either  temperatures calcium  all reactions  dry or carefully  were  chloride/  C 0  maintained (-20°C)  2  were  carried  flame-dried  by  use  out under  an  atmosphere  glassware.  of  the  [78], a c e t o n i t r i l e /  following C 0  2  baths  (-48°C),  [77]:  acetone/  ( - 7 8 ° C).  All  compounds  measurements  were  which  were  homogeneous  characterized  by  by glc and tic analyses.  45  high  resolution  mass  3.2  Solvents  and reagents  Solvents [79-80]  and reagents  and are summarized  Petroleum  ether  refers  Co-orporation  Aldrich  of  of  in  w a s also  hexane  to  procedure  slightly  was the  added mixture  dried  from  et  al.  acetonitrile of  modified [84]  w a s stirred  1  of  Alfa  Division  complex  standardized hydride  in  of  (DIBAH)  from  Aldrich  petroleum  ether,  To  reported  (recrystallized temperature  [7].  diiodide  freshly  under  from for  w a s prepared  triphenylphosphine of  that  in d r y a c e t o n i t r i l e  at r o o m  the as a  Chemical  from  1  ether  using  diiodide  iodine  in the presence  dry argon  before use.  30-60°C.  [82]. T r i p h e n y l p h o s p h i n e  triphenylphosphine  with  distilled  procedures  the  Ventron  were  obtained  double-titration 1.0 M  solution  Aldrich.  chloride/  3-lodo-2-cyclopenten-1-one tanedione  the  bromide  w a s obtained  methylene  Schank  azeotropically  from  established  were  between  [81]. D i i s o b u t y l a l u m i n u m  1,3-Cyclopentanedione  according  boiling  C o . , Inc. a n d w e r e  obtained  from  using  IV. A l l s o l v e n t s  methyllithium-lithium  Gilman  recrystallized  obtained  and dried  O r g a n o m e t a l l i c s , Inc.  Chemical  procedure  in T a b l e  was  or from  Solutions  purified  t o the fraction  Hexamethylditin  from  were  15 m i n  by  (prepared  distilled  ethyl  a  or  was  synthesized  w a s prepared stirred  acetate/  by  suspension  an atmosphere  of  a of  argon  methanol)  and  [83c-d].  refluxing as  C o . , Inc. a n d w a s  (4  h)  outlined  triethylamine  under  1,3-cyclopenabove) an  in  dry  atmosphere  [83].  T h i s order o f a d d i t i o n w a s f o u n d t o b e i m p o r t a n t a n d l e d t o i n c r e a s e the £-iodo enone ( s o m e t i m e s greater than reported y i e l d o f 85%).  46  in y i e l d  Table  IV:  Purification  of  solvents  Material  and  reagents  Drying  Reference  Agent  Acetonitrile  P 0 2  5  80a  Dichloromethane  P 0  5  79  2  ^/V-Dimethylformamide Dimethyl Diethyl  sulfoxide  1  1  ether  2  Hexane Tetrahydrofuran  1  Distilled  under  reduced  pressure  (12  Distilled  under  reduced  pressure  (0.2  Phenylthiocopper  for  seven  was  mmol) days.  washed  vacuum.  The  Copper method  of  CaH  2  80b  [85]  and The  2  CaH  2  80b  CaH  2  79  resultant  (I) House  was  with stored  (63  after  80a  4  80c  Torr) Torr)  g,  by  refluxing  0.57  mmol)  yellow  slurry  was  ethanol,  and  dried  under  argon  b r o m i d e - d i m e t h y l s u l f ide [86a],  2  Ph CO  prepared  thiophenol  thoroughly product  was  80a  Ph CO  LiAiH  2  0.25  80b  Na/  Triethylamine  g,  2  Na/  Hexamethylphosphoramide  (36  CaH  washing  in  the  complex  commercial  [86b].  47  a in  mixture absolute  filtered, for  the  several  absence  [86] cuprous  of  was  of  cuprous  ethanol  (1000  collected days  oxide ml)  material  under  high  light.  prepared  bromide  with  by  the  methanol  Cuprous further  cyanide  purification  Magnesium  white  bromide (from  was  was  Aldrich  in d r y ether.  powder  purchased  from  stored  Ether  prepared  Chemical was  cyclopentenyl)ethanol  under  argon  [88] (prepared  2-(2-cyclopentenyl)acetic with  acid)  triethylamine  with  stirred  dichloromethane,  Saturated s*50  mL of  under  basic  chloride.  3.3  procedures  3.3.1  Preparation  To (=*10 ether afford  a  without  addition  of  to a cold  under  high  freshly  distilled  (0°C) suspension of  vacuum  a n dt h e resultant  w a s prepared by  lithium  by  treatment  aluminum  hydride  triphenylphosphine  of2 - ( 2 -  reduction  dibromide  of  [89]  in  of  an atmosphere  prepared  b y treating  pyridinium o f argon  chloride  at  chlorochromate  f o r the preparation  (58%)  in  anhydrous  0°C.  (pH 8 ) w a s  hydroxide  2-(2-cyclopentenyl)-  prepared  to  1  L  b y the addition  of  o f trimethylstannyl  saturated  of  aqueous  reagents  of trimethylstannylIit hi urn  cold  (0°C) stirred  mL per mmol (1.0 equiv.). a pale  used  0°C.  suspension  ammonium  ammonium  Typical  C o . andwas  in a d r y box.  [90] w a s  ammonium  aqueous  C o . Inc.)  with  at  2 - (2-Cyclopentenyl)ethanal ethanol  Baker  by  removed  1- Bromo-2-(2-cyclopentenyl)ethane  acetonitrile  J.T.  [87].  1,2-dibromoethane magnesium  was  solution  o f hexamethylditin) T h e resulting  yellow  solution  of  hexamethylditin  was  solution  added  a solution  w a s stirred  o f trimethylstannyllithium  48  in d r y  o f methyllithium  at - 2 0 ° C [36].  tetrahydrofuran  f o r 15 m i n  in to  3.3.2  Preparation  of lithium  (phenylthiojftri methyl stannyl icuprate 8  [Me SnCuSPh]Li 3  8 To  a  prepared  (-20°C),  as outlined  portion was  cold  solid  stirred  above)  in 5  phenylthiocopper  stirred  at - 2 0 ° C  mmol) was  period  of  afford  3.3.4  cold  and phenylthiocopper  slowly  added 2  d r y tetrahydrofuran  afford  stirred  of methyllithium  w a sadded  T h e resulting  dark  in  yellow  red solution  one  slurry  of  solution  mixture  of  lithium  hexamethylditin (0.39  in 5 m L o f d r y tetrahydrofuran,  ( 2 9 5 jt*1. 1 . 3 2 M , 0 . 3 9 m m o l )  w a s stirred  o f the phenylthiocuprate  of lithium  a  (0.39 mmol,  8 [29].  (-78°C),  m i n . T h e resulting  Preparation  trimethylstannyllithium  (67 m g , 0.39 m m o l )  1 equiv.  a redsolution  mL of  f o r 15 m i n t o  to a  of  (67.3 m g ,0.39 m m o l ) .  (phenylthio)(trimethylstannyl)cuprate  Alternatively,  solution  at - 2 0 ° C  over  f o r 30 m i n  a to  8.  (cyano)ftrimethylstannyl)cuprate  74  [Me SnCuCN]Li 3  74 To  a  prepared portion  cold  (-78°C),  as outlined solid  cuprous  stirred  at - 7 8 ° C  yellow  solution  above)  solution  in 5  cyanide  for 5  to  mL of  (34.9  of  trimethylstannyllithium  dry tetrahydrofuran  m g ,0.39 mmol).  m i n a n d then  o f the cyanocuprate  Alternatively, mmol)  stirred  74  a  cold  -78°C,  and azeotropically  dried  (toluene)  at - 4 8 ° C  (0.39 m m o l ,  w a sadded  T h e resulting  in  one  mixture w a s  f o r 15 m i n t o a f f o r d  a  bright  (0.39 m m o l ) [49].  stirred cuprous  49  solution cyanide  of  hexamethylditin (0.39  (0.39 m m o l )  in 5 m Lo f  dry  tetrahydrofuran,  0.39  mmol)  was  stirred  3.3.5  over  was slowly  a period  at -48°C  Preparation  added  of 2  1 equiv.  m i n . T h e resultant  f o r 30 min t o give  of dilithium  o f methyllithium flocculent  (277 yellow  n\,  1.41  M,  suspension  thecyanocuprate 74.  (cyano)lmethyl)(trimethylstannyl)cuprate  [Me Sn(Me)CuCN]Li 3  78  2  78  To 80  a cold  (-78°C),  stirred  (0.39 m m o l ,  prepared  a s outlined  added  a solution  stirred order  o f methyllithium  Alternatively,  with  and cuprous  toluene  to  a  cold  cyanide  homogeneous  tansolution  Preparation  Using  in 5 m L o f d r y tetrahydrofuran  (0.39 m m o l ) .  a homogeneous  (-78°C),  stirred  The resulting tan solution  solution  (34.9 m g , 0.39 m m o l ) ,  [87], in 5 m L o f d r y tetrahydrofuran, T h eresulting  3.4.1  in ether  (cyano)(trimethylstannyl)cuprate was  mixture w a s o f t h e higher  7 8 (0.39 m m o l ) .  methyllithium.  3.4  o f lithium  above)  at - 2 0 ° f o r 15 m i n t o a f f o r d cyanocuprate  mmol)  solution  mixture o f higher  w a s stirred order  was slowly  order  cyanocuprate 7 8  0  SnMe  14  50  azeotropically added  3  dried  2 equiv. o f  f o r 30 m i nt o afford  7 8 (0.39 m m o l ) .  of 3-trimethylstannyl-2-cyclopenten-1-one  the higher  hexamethylditin (0.39  previously  at - 2 0 ° C  cuprate  of  14  a  To mmol,  a  cold  prepared  atmosphere  argon,  temperature  only  desired  concentration  of  ^-trimethylstannyl  enone  respectively)  showed  this  were  3.5  Large  scale  3 . 5 . 7 Using  To cuprate  a 8  g e l ,eluting  identical with  under  fractions  the presence  mmol,  those  added,  and the mixture  with  reported  stirred  an  oil which  added,  at  with  anhydrous  petroleum  magnesium  o n g l c analysis  67  (silica  Flash  ether-ether, 4:1),  (air-bath  afforded  room  saturated  hexamethylditin.  and distillation  material  vigorously  mg  temperature  (83%) o f t h e  gel and column  The spectral  properties  B, of  earlier [38].  of 3-trimethylstannyl-2-cvclopenten-1-one  14  8  solution  prepared  3-iodo-2-cyclopenten-1-one at - 7 8 ° C  (10 m L )w e r e  some  of one component.  an atmosphere  stirred  by  under  f o r 60 m i n . Saturated  over  yellow  (0.39  w a s stirred at  w a s washed  a n d dried  a pale  78  3-iodo-2-cyclo-  tan solution  1 4 [29]. T i c a n d g l c a n a l y s i s  (-78°C),  (4.0  layer  accompanied  the reduced  preparation  cold  dark  mL) of  (in t h e f u m e h o o d )  afforded  cuprate  dry tetrahydrofuran,  (2 m L ) a n d e t h e r  chloride,  silica  the phenylthiocuprate  tetrahydrofuran, of  of  order  (THF, 1  T h e ether  the appropriate  0.02 Torr)  material  g  mL of  solution  chloride  product  [76] (3  t h e higher  T h e resulting  minutes.  of the solvent  chromatography  61-72°C/  a  (pH 8) a m m o n i u m  Removal  in 5  w a s stirred  f o r several  basic  showed  mixture  of  f o r 6 0 m i n , a n d at 0 ° C  (pH 8 ) a m m o n i u m  the resulting  sulfate.  w a s added  (69 m g ,0.33 mmol).  basic  aqueous  solution  above)  f o r 90 m i n , at - 4 8 ° C  aqueous and  stirred  as outlined  of  penten-1-one -78°C  (-78°C),  as  of  lithium  outlined  o f argon,  (phenylthio)(trimethylstannyl)-  above)  w a s added  7 5 (728m g , 3.5 mmol).  f o r 3 h. M e t h a n o l w a s stirred  in  51  temperature  mL  of  dry  a solution  (THF, 5m L )  T h e resulting  mixture w a s  (^2 m L ) a n d petroleum at r o o m  50  ether  (200 m L ) were  f o r several  minutes. T h e  resultant  yellow  100-200 ether the  mesh).  solvent  the  one  was  after  100 a  product,  this  Preparation  through  eluted ether  oil  (30  g  of  the  mg  were  gel,  of  column  further  3  eluate  x  was  basis  elution  fractions  glc  those  analysis  (20  Removal  of  (column  B),  of  oil  this  ether-ether,  enone  (air-  14.  earlier  g,  petroleum  Subjection  reported  3-trimethylstannyl-2-cyclopenten-1-ol  SnMe  of  distillation  trimethylstannyl with  mL  petroleum  and  Florisil  combined.  of  with  of  100  hexamethylditin.  the  identical  short  the  by  appropriate  (82%)  a  the  w h i c h , on  silica  a  with  and  accompanied  material  of  of  yellow  material, 703  of  was  mL  concentration  residual  filtered  column  chromatography  properties  3.6  by  afforded  of  flash  gave  The  followed  consisted to  slurry  The  4:1)  bath)  of  spectral  [38].  81  3  81  3.6.1 Small To  scale  a  cold  (0°C),  cyclopenten-1-one atmosphere hydride h  [61].  in  of hexane  Sodium  14  (78  argon, (0.38  mixture  was  vigorously  formed.  The  inorganic  several  portions  mg,  was  0.32  mmol)  The  salts  for  were  ether.  mixture in  dropwise resulting  decahydrate stirred  hot  stirred  added  mmol).  sulphate  of  vigorously  a  mL  removed  mixture  minutes by  combined  52  3-trimethylstannyl-2-  of  solution  (powdered)  several  The  5  of  was  was until  filtration filtrate  dry  hexane,  of  diisobutylaluminum  stirred added a  0°C  were  an  for  1.75  and  the  precipitate  had  carefully  white  and was  at  under  washed  concentrated  with under  reduced of  pressure  the residual  81.  (aspirator).  Distillation  o i l afforded  7 8 m g (98%) o f  T i c and g l c analysis  presence  (silica  o f one component.  This  material  c m - ; »H n m r ( 4 0 0  Hz),  1.48 (br. s , 1 H , - O H , e x c h a n g e s  1 J  H), 2.34-2.44 r  2  M H z , CDCI )  c  found:  =  u  35/39  with  42-52°C/  0.02  Torr)  3-trimethylstannyl-2-cyclopenten-1-ol B, respectively)  exhibited  ir ( f i l m )  6 : 0.16 (s, 9 H , stannyl  3  ( m , 1 H), 2.56-2.67  Hz, J on—n  temperature  gel and column  767  1  (air-bath  D 0 ) , 1.61-1.71  showed  : 3290,  the  2880, 1690,  methyls,  i  S  _  n  = 55  H  ( m , 1 H), 2.19-2.29 ( m ,  2  ( m , 1 H), 4 . 8 8 (br. m , 1 H ) , 5.94 (br. d , 1 H ,  Hz). Exact  Mass  calcd.  for C,H  1 6  OSn  :  248.0223  ;  248.0233.  3.6.2 Large scale To  a  cold  (-78°C),  cyclopenten-1-one argon,  was  added  diisobutylaluminum was  stirred  ether  hydride  at 0 ° C  resultant aspirator). x  for 2  added  Anhydrous  w a s filtered  The collected  (air-bath)  the  of  aqueous  a n d the mixture magnesium a  with  oil  several  (ir,  described  identical  with  those  53  above.  chloride  under  (1  under 755  properties  of  mixture mL)  until  a  and  white  and  suction  portions  under  solution  w a s added  celite  afforded  ether  T h e resulting  sulphate  pad of  a  w a s stirred  w a s concentrated  residual  3-trimethylstannyl-2-  min  ammonium  81. T h e s p e c t r a l  H nmr) were  5  (4.0 m L , 4.0 mmol).  3-trimethylstannyl-2-cyclopenten-1-ol J  of  in 30 m L o f d r y diethyl  w a s washed  filtrate  solution  period  through  material  of  a  h. S a t u r a t e d  10 m L ) . T h e c o m b i n e d  Distillation  over  in hexane  carefully  w a s formed. mixture  stirred  (788 m g , 3.22 m m o l ) dropwise  (60 m L ) w e r e  precipitate  (10  14  vigorously  the  (water  o f hot ether  reduced mg  pressure. (95%) o f  o f this  material  3.7  Preparation  To 0.31  a  3-ferf-butvldimethvlsiloxy-1-trimethylstannvlcvclopentene  stirred  mmol)  argon,  of  in  solution  1  w a s added,  mL  stirred  aqueous extract  at  room  with  magnesium  chromatography  Fractional  distillation temperature  58-60°C/  0.2  Torr)  of  0.15  1090, 778 c m " (s, 9  H, stannyl  the  Removal  of 1  ;  83  (m,  1  with  110 as  Torr) mg a  the  and  colorless  one compound.  This  material 3  J _  H), 2 . 1 6 - 2 . 2 6  ,,  =  56  5% (W/V)  The  combined  and dried  followed  product,  sublimed  mixture had  with  ether-ether,  by  9:1) gave a  of  over flash after  colorless oil.  rerr-butyldimethylsilanol (air-bath  temperature  3-fe/-f-butyldimethylsiloxy-1-tri-  liquid.  »H n m r ( 4 0 0 M H z , C D C I ) methyls,  solvent,  distillation  (97%) o f  atmosphere  ether.  remove  (76.5 m g ,  and freshly  bicarbonate  the desired to  81  the reaction  with  petroleum  product  12  —  1.56-1.67  sodium  of  an  w a s diluted  extracted  containing  crude  After  m i n , it  5 % ( W / V ) aqueous  provided  the presence  90  and thoroughly  =*60°C/  methylstannylcyclopentene  1583,  for  g e l , elution  under  ( 0 . 1 1 g , 1.6 m m o l )  (49 m g , 0.32 m m o l ) .  all the fractions  (air-bath  showed  imidazole  sulphate.  (4 g , s i l i c a of  /V,/V-dimethylformamide,  temperature  bicarbonate  w a s washed  concentration  dry  chloride  sodium  anhydrous  of  3-trimethylstannyl-2-cyclopenten-1-ol  successively,  te/?-butyldimethylsilyl been  of  83  Glc  analysis  exhibited  6 : 0.097  (s, 6  Hz), 0.93 (s, 9  ir  (column (film):  H, silyl  H, silyl  A) 2893,  methyls), rerr-butyl),  an-n  (m,  1 H), 2.26-2.38  54  (m,  1  H), 2.55-2.66  (m,  1 H),  4.95  ( m , 1 H ) , 5.82 (br. d , 1 H , J  MHz,  CDCIj,  methyls),  S  H broad  carbons),  Exact  calcd.  Mass  General  forC  procedure  Preparation with  79.45  of  1 0  H  2 1  2 Hz, J  decoupled)  8:  carbon),  25.67  1 7 . 9 8 (quaternary  (methylene  3.8  band  =  =  3 6 / 4 0 Hz).  (stannyl  (tert-buty\  143.95  3  (M -  u  -10.83  (-CH(OSiR )-). OSiSn  c  an-n  methyls), 3  l  C nmr  methyls),  (=C(SnMe )-).  B u ) : 305.0384;  +  1 3  found:  (20.15  - 5 . 1 0 (silyl 34.09,  148.22  36.90 (=CH-).  305.0384.  A  1-1' ithio-3-tert-butvl  dimethyl si loxvcvclopentene  84  and  its  reaction  electrophiles  t  84 To  a  cold  (-78°C),  1-trimethylstannylcyclopentene tetrahydrofuran, of  methyllithium  stirred  A  solution  reaction  solution  (98  of  m g , 0.27 mmol)  o f argon,  w a s added,  ( 2 2 0 j z l , 1.47 M , 0 . 3 2 m m o l ) .  f o r a period  3-rerr-butyldimethylsiloxy-  o f 1 h. A  colorless  in  3  dropwise,  The resulting solution  mL a  of dry solution  mixture w a s  o f the vinyllithium  resulted.  84  tetrahydrofuran  83  an atmosphere  in ether  at - 7 8 ° C  intermediate  the  under  stirred  of  t h e appropriate  (0.5 m L ) w a s added.  mixture  w a s stirred  electrophile  When  at - 7 8 ° C  55  (1.3 equivalents)  theelectrophile f o r 1 h, w a r m e d  w a s a n alkyl to room  in dry halide,  temperature  over  a  period  bicarbonate at  -78°C  for  3.9  h,  and  then  carbonyl  1 h, a n d treated  with  saturated sulfate.  product  Preparation  aqueous  Removal  of  with  saturated  electrophiles, the reaction temperature  mixtures  sodium  of  w a s purified  quenched  at t h i s  (0.3 m L ) . T h e r e s u l t i n g  magnesium reaction  1  (0.3 m L ) . W i t h  bicarbonate washed  of  the  with  were  by simple  mixture  saturated  immediately  bicarbonate,  solvent  aqueous  and  afforded  distillation  a  sodium  w a s stirred  aqueous  diluted  sodium  with  dried  over  pale  yellow  ether,  anhydrous oil. The  (air-bath).  "l-/7-butvl-3-re/ r-butvldimethvlsiloxvcvclopentene  96  -  96  Following  the  vinyllithium  reagent  allowed  to  react  mL)  -78°C  at  followed  by  general  procedure  8 4 (prepared with  for  1  h,  and  (air-bath  oil  afforded  54  mg  the  presence  of  one compound.  c m  silyl  methyls),  methyl),  1  ;  W  at  (60%) o f  1.25-1.37  9  H,  3  56  h.  (m, 2  Normal  0.5 T o r r )  of  (column  ir ( f i l m ) :  0.88-0.92  of  tetrahydrofuran  T M S as standard)  methyls),  1.39-1.48  1  mmol  the  methyllithium) w a s  in  glc analysis  exhibited  external  te/?-butyl  0.27  83 with  for  55-60°C/  96. A  material  (m, 2 H, -C£L-CH ),  of  temperature  compound This  above,  0.35 m m o l )  uL,  temperature  3  (s,  (40  room  n m r (400 M H z , C D C I , 0.90  outlined  the reaction  1-bromobutane  distillation  1069  from  A  workup,  the  residual  B)  showed  2910, 1650, 6:  (m,  1263,  0.08 (s, 6 H, 3  H,  H, -C£L-CH -CH ), 2  (3  3  terminal 1.62-1.72  (m,  1 H), 2.32-2.41  Hz).  Exact  3.10  Mass  calcd.  Preparation  pentene  ( m , 1 H ) , 4 . 8 8 (br. m , 1 H ) , 5 . 3 4 ( d , 1 H , v i n y l for CnHjjOSi  of  (M* -  Bu*): 197.1361;  found:  1-J_2-(2-cyclopentenvl)ethvn-3-ferr-butvldi  proton,  J  =  1  197.1358.  methyls iloxycyclo-  97  97 Following vinyllithium  the  general  reagent  procedure  (prepared  84  as  1-bromo-2-(2-cyclopentenyl)ethane hexamethylphosphoramide and  room  added The  temperature  and  dried  reduced  B)  showed  0.35 m m o l )  oil afforded  the presence  of  aqueous  sodium  sulfate.  aqueous  1  material  of  m, 8  H,  vinylic  3  H, fe/Y-butyl  methyls),  1.35-1.73  H), 2 . 6 4 (br. m , 1 H , a l l y l i c  Mass  -CH(OSiR )-CH =CR-), 3  calcd.  for C  1 9  H  3 2  OSi  tertiary  6.50-6.70  : 292.2222;  57  6:  (series  of  A  ether  the  the with  of  dry  for  1 h,  mL)was  (2 x  10 m L ) .  sulfate  (10 m L )  solvent  under  0.2  glc analysis  H, silyl  Torr)  (column  ir ( f i l m ) :  H), 2 . 0 0 - 2 . 4 3  2903,  methyls), (series  4 . 8 8 (br. m , 1 H ) , 5 . 3 0 ( m , 1  H, cyclopentenyl  found:  (1  71-75°C/  exhibited  m, 4  react  at - 7 8 ° C  0.08 (s. 6 of  proton),  (m, 2  97.  to  of  presence  copper  temperature  the ether This  mmol  bicarbonate  Removal  distillation (air-bath  one component.  the  extracted with  saturated  5 7 m g (72%) o f  in  in t e t r a h y d r o f u r a n  w a s thoroughly with  0.27  w a s allowed  m g , 0.35 mmol),  magnesium by  above,  above)  1 2 5 0 , 1 0 3 0 c m - ; »H n m r ( 4 0 0 M H z , C D C I ) (s, 9  Exact  (61  w a s washed  followed  outlined  outlined  h. S a t u r a t e d  mixture  anhydrous  pressure,  the residual  0.90  extract  over  of  1636,  for 4  and the resultant  combined  (61 uL,  A  292.2218.  olefinic  protons).  3.11  Preparation  of  1-(1-hvdroxvcvc Iohexyl)-3-fe/'f-butvldimethylsi loxvcvclopentene  98  )Si(Me JBu }  98  Following reagent with  8 4 (prepared  workup,  the residual  (column (film):  B) 3360,  methyls), H), =  by (37  followed  showed 2905,  the  (m, 3  2 Hz). Exact  Preparation  of  M L , 0.35 by  A  8 3 with  mmol)  distillation 52  above,  mg  presence  in  the silyl  component.  methyls),  1 7  H  2 9  0 Si  (M  2  3  +  -  (broad  vinyllithium  -78°C  to for  1  0.1  Torr)  90-95°C/ 9 8 . A  h.  glc analysis  material 6:  react  exhibited  0.07 (s, 6  unresolved  H,  ir  silyl  signal,  15  5 . 5 5 (br. d , 1 H , - C H = C R - ,  3  for C  (CDCI )  1.27-2.71  H), 4 . 8 9 ( m , 1 H, - C H ( O S i R ) - ) . calcd.  at  ether This  the  w a s allowed  temperature  1  H, ferf-butyl  of  tetrahydrofuran  (air-bath  one  mmol  methyllithium)  (78%) o f  of  0.27  1 6 1 8 , 1 2 2 7 , 1 0 3 9 c m - ; MH n m r  Mass  of  procedure  reaction  oil afforded  1.27 ( s , 9  2.02-2.71  3.12  general  cyclohexanone  Normal of  the  C H ) : 293.1934; 3  found:  J  293.1937.  1-(1-hydroxvcvclopenty I)-3-fe/~f-butyldimethylsi loxvcvclopentene  99 )Si(Me )Bu 2  9 9  58  t  Following reagent with  84  the general  (prepared  cyclopentanone  Normal  workup,  of  residual  the  (column (film):  B)  3.13  the  =  of  outlined  83 with  0.35 m m o l )  by  distillation  60  mg  presence  in  silyl  component.  m,  2  3  H), 4.90  Hz). Exact  methyls), (br.  Mass  m,  calcd.  1  H,  6:  C  1 6  H 0 Si 27  (M  2  1  0.1  Torr)  (s, 6  5.59 -  +  H,  ir  silyl  signal,  10  d,  H,  (br.  CH ):  h.  analysis  exhibited  unresolved  3  react  for  glc  0.11  -CH(OSiR )-).  for  A  material  (broad  to  -78°C  99.  This 3  1.32-2.10  vinyllithium  84-87°C/  ether  1  H, fe/?-butyl  at  temperature  the  of  w a s allowed  tetrahydrofuran  (air-bath  one  0.27 m m o l  methyllithium)  (77%) o f of  above,  1 6 1 9 , 1 2 2 7 , 1 0 3 7 c m - ; >H n m r ( C D C I )  (br.  J  A  iiL,  o i l , gave  0.93 (s, 9  -CH=CR-, found:  followed  2930,  2.10-2.67  reaction  (31  showed  3330,  methyls), H),  by  procedure  1  267.1780;  3  267.1781.  Preparation  of  1-M-hvdroxy-2-(2-cvclopentenyl)ethyn-3-rert-butyldi  methyl-  si l o x y c y c l o p e n t e n e 100  100  Following vinyllithium allowed  general  reagent  84  react  with  to  tetrahydrofuran (air-bath  the  procedure  (prepared  outlined  reaction  of  2-(2-cyclopentenyl)ethanal  (3 m L ) a t - 7 8 ° C  temperature  by  A  138-145°C/  for 0.2  1 h. N o r m a l Torr)  59  of  above, 83  with  (37  workup,  the  0.27  mmol  methyllithium)  mg,  0.35  followed  residual  of  oil  mmol)  the was in  by distillation  afforded  51  mg  (61%)  o f the hydroxy  silyl  presence  o f t w o major  ir  3375,  (film):  silyl 11  methyls),  components  in a ratio  tert-butyl  General  Preparation  (M +  procedure  of  the  methyls), with  5.50-5.88  3  7  of 4  (column  : 5.5. This  1  0.88 (s, 9 H ,  f o r Ci H„OjSi  glc analysis  B) showed the material  1 6 2 9 , 1 6 0 5 , 1 2 2 5 , 1 0 2 8 c m " ; >H n m r ( C D C I )  4.87 ( m , 1H, -CH(OSiR )-),  calcd.  A  100.  H), 2.02 (s, 1 H, - O H , exchanges  Hz),  3.14  2930,  ether  CH ): 293.1936; 3  8 : 0.11 ( s , 6 H ,  3  1.12-3.0  (broad  unresolved  D j O ) , 4 . 4 6 (br. t , 1 H , - C H O H , (m, 3  H, vinylic  found:  293.1930.  exhibited  protons).  signal, J  Exact  =  6  Mass  B  phenylthiocuprate  ketones and f}-iodo-a,p-unsaturated  103  and  its  reaction  a p-unsaturated  with  ketones  SPh  103 To  a  cyclopentene mL mg,  cold  0.27 m m o l ) . a  yellow  (phenylthio)cuprate  A  stirred  8 4 (0.27 m m o l ,  of dry tetrahydrofuran  afford  mL)  (-78° C),  solution  w a s added  prepared  w a s added  T h e resulting solution  solution  of  yellow lithium  of  1-lithio-3-fe/-f-butyldimethylsiloxy-  a s outlined  in general  in o n eportion, slurry  solid  w a s stirred  procedure  A ) in 3  phenylthiocopper at - 7 8 ° C  (46.6  for 1 h to  (3-terf-butyldimethylsiloxy-1-cyclopentenyl)-  103.  o f the appropriate a n d the mixture  enone  (0.25 m m o l )  w a s stirred  60  for 3  in d r y tetrahydrofuran  h at -78°C.  Methanol  (<*1 (=*0.5  mL)  and petroleum  warm  to room  column dried  reduced elution afforded  3.15  pressure.  petroleum  pure  General  Preparation  with  magnesium  Column  added  T h e resulting  (5 g , e l u t i o n  anhydrous  with  (15 m L ) were  temperature.  o f Florisil over  ether  yellow  petroleum  sulfate  3:1)  slurry  ether).  of  w a sallowed t o  w a s filtered  The combined  and the solvent  chromatography  ether-ether,  a n dthe mixture  t h e residue  and distillation  through  eluate w a s  w a sremoved o n silica  a  under  g e l (8 g ,  o f t h e o i l thus  obtained  product.  procedure  C  of the cyanocuprate  104 and its reaction with enones and f)-iodo enones  I  104 To  a  cold  siloxycyclopentene 3  (-78°C), 84  (0.27 m m o l ,  m L o f d r y tetrahydrofuran  [87]  (24 m g ,0.27 mmol).  afford  a  pale  yellow  pentenyl)(cyano)cuprate  Alternatively,  to  stirred  prepared  w a s added  T h e resulting solution  of  0.27 m m o l )  of  a s outlined  1-lithio-3-terY-butyldimethylin general  in o n e portion,  mixture lithium  w a s stirred  solid  procedure cuprous  at -78°C  A ) in cyanide  for 1 hto  (3-terr-butyldimethylsiloxy-1-cyclo-  104.  a  cold  (-78° C),  -3-te/-r-butydimethylsiloxycyclopentene mg,  solution  in d r y tetrahydrofuran  stirred  83  solution  (0.27 m m o l )  1-trimethylstannyl-  a n d cuprous  (3 m L ) , w a s a d d e d  61  of  cyanide (24  methyllithium  in ether  (489  / x i , 1.32 M , 0.27 m m o l ) .  min  a n dat - 2 0 ° C  A mL) to  solution  chloride  f o r 30 min t o yield  o f the appropriate  w a s added -48°C,  a n dthe resulting  and stirred  at this  (pH 8 ) a n d ether  warm  to  room  saturated sulfate.  ammonium  Evaporation  of  enone  added  at -78°C  solution  followed  by  f o r 15  in d r y tetrahydrofuran  aqueous  twice  anhydrous  column  the apropriate  ammonium  w a s allowed to  w a s washed over  (1  f o r 1 h, w a r m e d  a n d the mixture  (pH 8) and dried  from  at - 7 8 ° C  104.  f o r 3 h. S a t u r a t e d  T h e resulting  obtained  cuprate  w a s stirred  temperature  the solvent  w a s stirred  (0.25 m m o l )  solution  chloride  o f the material  solution  thedesired  (15 m L )were  temperature.  aqueous  distillation  T h e resulting  magnesium  chromatography  fractions  with  and  afforded  pure  product.  3.16  General  Preparation  procedure  of  the  conjugate addition  D  Grignard  reagent  105  from  84  and  its  copper  (IJ  catalyzed  to enones  OSifMe^u  1  MgBr  105 To  a  cold  cyclopentene in  3  84  mL of  anhydrous  (-78°C),  stirred  (0.27 m m o l ,  prepared  d r y tetrahydrofuran  magnesium  bromide  solution  of  1-lithio-3-re/-r-butyldimethylsiloxy-  as outlined  under  an atmosphere  (53 m g , 0.29 mmol).  62  above  in general of  procedure  argon,  The resulting  white  A )  w a s added slurry w a s  stirred  at  -78°C  for  1  h  to  afford  siloxy-1-cyclopentenylmagnesium  Copper  (I)  30  mL  tetrahydrofuran).  -78°C  for  ether  (15  room  3.17  h.  8)  blue.  aqueous of  by  The  Saturated  m L ) were  pale  Evaporation pure  3  temperature.  became (pH  min), followed  the solvent  of  yellow-red  stirring  The organic  complex  layer  chloride, followed  (30  3-ferr-butyldimethyl-  aqueous  resulting was  thus  mixture  maintained  and dried  enone  over  distillation  chloride  until  the  washed  with  of  was  w a s allowed  anhydrous  was  (0.25 m m o l  obtained  ammonium  w a s separated,  by  m g , 0.15 m m o l )  appropriate  solution  (pH 8 )  reagent,  105.  solution  and the  Vigorous  ammonium  a  basic  added  Grignard  bromide,  bromide-dimethylsulfide  (-78°C, of  the  in  stirred  (5 to  warm  oil  at  to  phase  saturated  magnesium  1  mL) and  aqueous  the residual  added  basic  sulfate. afforded  product.  Preparation  of  3-(3-rerr-butyldimethvlsiloxv-1-cyclopentenyl)cvclopentanone  106  106  63  3.17.1 Using  the phenylthiocuprate  Following mg, by  0.33  mmol)  column  petroleum Torr)  ether:  petroleum  1544,  0.89  2.05-2.50  -CH(OSiR )-), 221.0998;  The  1  H,  ether  product  106. N o r m a l  o n silica  (air-bath  a s a clear  2 - c y c l o p e n t e n - 1 - o n e (27  o n e spot.  temperature,  colorless  This  oil.  material  »H n m r ( 4 0 0 M H z , methyls),  signal,  8  CDCI ) 3  1.60-1.88  Mass  calcd.  followed  analysis  showed  (developing  exhibited  solvent,  ir ( f i l m ) :  5 : 0.07 (s, 6 unresolved  H  1 2  1 7  0 Si 2  2830,  H, silyl m , 2 H),  H ) , 4 . 9 3 (br. m ,  for C  with  185-190°C/ 0.4  Glc  (broad  H), 2.88 (m, 1  ( m , 1 H). Exact  workup  g e l (8 g , e l u t i o n  a n d the t i c analysis  te/?-butyl  unresolved  1 H,  (M*-  Bu*):  221.1000.  t h e general  o f the keto l  cm" ;  above,  the cyanocuprate 104  Following (65%)  (s, 9  found:  3.17.2 Using  o f 106  3:1) gave  5.41-5.40  3  the keto  3:1)and distillation  1045  (broad  into  one component  ether,  1225,  B outlined  o f t h e crude  m g (72%)  of  ether:  methyls),  converted  ether,  54.4  presence  1715,  was  procedure  chromatography  yielded  the  the general  103  ether  procedure 106  H n m r a n d ir s p e c t r a  from  were  C outlined  above,  2 7 m g (0.33  identical  with  there  mmol) those  was  of  obtained  49  mg  2-cyclopenten-1-one.  o f the material  described  above.  3.17.3 Using  the Grignard  Following desired  keto  t h e general  procedure  ether  was  2-cyclopenten-1-one. material  reagent 105  described  106  D  outlined  obtained  from  T h e i r a n d >H n m r s p e c t r a  above.  64  above,  were  27  52 mg  identical  m g (69%)  of the  (0.33 m m o l )  of  with  the  those  of  3.18  Preparation  of 3-(3-fe/Y-butyldimethylsiloxv-1-cvclopentenvl)cvclohexanone  107  107  3.18.1 Using  the phenylthiocuprate  Following mg, by  0.33  mmol)  column  1703,  ether-ether,  proton).  the keto  o f t h e crude  3:1) and distillation  o i l .G l c analysis  (column  B) of  in t h e ratio  ether-ether, 1250,  signal,  Exact  3:1) gave  1038 c m - ; 1  calcd.  ether  o n silica  (air-bath  this  which  temperature o f ether  material  methyls),  3  1.53-1.74 3  H  2 1  0 Si 2  (M +  65  Bu*):  followed  6:  (m, 2 5.43  237.1311;  with  78-81 ° C /0.15 107  as a  clear,  it c o n s i s t e d  (developing  exhibited  CDCI )  (br. m , 1 H , - C H ( O S i R ) - ) , 1 3  that  o n t i c analysis This  workup  (33  g e l (8 g , e l u t i o n  oil showed  *H n m r ( 4 0 0 M H z ,  for C  2-cyclohexen-1-one  107. N o r m a l  7 2 m g (91%)  o n e spot.  H, ferr-butyl  10 H ) , 4 . 8 8  Mass  2.6:1,  above,  product  gave  0.88 (s, 9  unresolved  outlined  obtained  1620,  methyls),  into  B  thus  components  petroleum  procedure  converted  o f the material  colorless two  was  chromatography  petroleum Torr)  the general  103  solvent,  ir ( f i l m ) :  0.50 (s, 6 H), 1.91-2.50  of  2920,  H, silyl (broad  (br. m , 1 H , o l e f i n i c found:  237.1305.  3.18.2 Using  the cyanocuprate 104  Following of and  the keto l  ether  H n m rspectra  3.18.3 Using  desired  keto  3.19  material  107  C  above,  material  were  of  w a s obtained  63 m g  of 2-cyclohexen-1-one.  identical with  those  described  (80%)  The  above.  reagent 105  procedure  w a s obtained  D  outlined  from  l  described  there  33 m g (0.33 m m o l )  T h e ir a n d H n m r s p e c t r a  Preparation  en-1-one  o f this  t h e general ether  hexen-1-one.  procedure  from  107  the Grignard  Following  the  t h e general  above,  6 7 m g (85%) o f t h e  33 m g (0.33 m m o l )  obtained  were  identical  of  with  2-cyclothose  of  above.  3-(3-fert-butvldimethylsiloxy-1-cyclopentenvl')-2-cyclopent-  108  108  66  ir  3.19.1 Using  the phenylthiocuprate  Following  the  cyclopenten-1-one 108. N o r m a l silica  colorless  nmr  This  material  (400 MHz.  methyls),  1.75-1.85  2  H z , vinyl  278.1702;  found:  3.19.2 Using  Torr)  exhibited  ir ( f i l m ) :  2946,  into  (74%) o f  the presence  petroleum 1707,  Exact  the enone  product o n  a  clear  o n e component  ether-ether,  3:1) gave o n e  1624,  1640,  1260,  1076  0.90 (s, 9  c m - ; »H 1  H. ferf-butyl  ( m , 3 H ) , 5.00  o f enone). Mass  (air-bath  as  108  ether  of  methyls),  proton  3-iodo-2-  o f t h e crude  ( m , 4 H), 2.65-2.88  ether).  above,  3:1) a n d distillation  55.4 m g  H, silyl  5.99 ( s , 1 H , v i n y l  calcd.  6.19  (br.  m,  (br. d , 1 H , J  for  C H u  2 t  0  2  l ,  Si  278.1703  the alternative  5 4 m g (72%)  procedure  o f enone  enone  7 5 . T h e i r , •H n m r s p e c t r a  3.20  Preparation  en-1-one  solvent,  allyl  converted  B) showed  (m, 1 H), 2.30-2.48  of  was  ether-ether,  6: 0.09 (s. 6  proton  outlined  chromatography  yielded  (column  B  the cyanocuprate 104  Following obtained  by column  (developing  CDCI,)  mmol)  petroleum  0.01  H, -ChtfOSiBuW,)-).  =  with  o i l .G l c analysis  the t i c analysis  spot.  1  88-93°C/  procedure  m g , 0.33  followed  g e l (8 g , e l u t i o n  temperature  and  general  7 5 (68.6  workup  103  of  ether were  i n general  108  from  procedure  68.6  identical with  m g (0.33 those  C above, mmol)  described  there w a s  o f the iodo above.  3-(3-fe/t-butyldimethylsiloxy-1-cvclopentenyl')-2-cvclohex-  109  109 67  3.20.1 Using  Following one  7  g,  the general  followed  by column  elution  with  petroleum  98-107°C/  0.01  Torr)  (column  B ) o f this  analysis material CDCIj (m, H), 2  exhibited  Exact  solvent,  ir ( f i l m ) :  that  calcd.  o f a clear,  0.89  product  1255  (s, 9 H,  em- ; 1  tert-butyl  oil.  found  6.09  (8  G l c analysis which  o n e spot. l  gel  temperature  on  tic  This  H n m r (400 MHz,  methyls),  1.70-1.81  ( m , 2 H), 2.44-2.69  o f enone),  : 292.1859;  68  (air-bath  3:1) gave  109. Normal  o n silica  o f one component,  1598,  proton  ether  colorless  ( m , 2 H), 2.37-2.42  H ,0,Si }  o f t h e crude  1608,  (s, 1 H, vinyl 1 7  3-iodo-2-cyclohexen-1-  the enone  ether-ether,  1668,  methyls),  for C  into  it c o n s i s t e d  petroleum  2930,  above,  3:1) and distillation  7 1 . 1 m g (89%)  ( m . 2 H ), 2 . 2 6 - 2 . 3 7  Mass  outlined  converted  ether-ether,  gave  (br. m , 1 H ) , 5.93  B  chromatography  6 : 0.08 (s, 6 H , silyl  4.96  was  oil showed  (developing  1 H ) , 2.01  Hz).  procedure  (73.3m g , 0.33 m m o l )  workup  103  the phenylthiocuprate  (m, 3  (br. d , 1 H , J  292.1860.  =  REFERENCES 1.  For a review Chem.,  2.  3.  Int.  Ed.  E. E l k i k  (c)  C. Kashima  (b)  M.I-. and  Zhou  and  64,  2543  Huang,  Bull.  J.  12,  Chem., Sum  and  N. Fukamia, Casey,  variation,  325  Chim.  439  Fr.,  Angew.  (1976) 52,  Chem. Soc. Jpn., 12,  Commun.,  L. W e i l e r ,  795  (a) G.H.  Posner  and  D.J.  (b)  R.M.  Coates  and  L. 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