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

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SYNTHESIS AND CHEMISTRY OF ALKYL 2,3-BIS(TRIMETHYLSTANNYL)-2-ALKENOATES AND RELATED SUBSTANCES By RENATO TONY SKERLJ B.Sc. (Hons.), University of Otago, New Zealand, 1982 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE STUDIES DEPARTMENT OF CHEMISTRY We accept this thesis as conforming to the required standard THE UNIVERSITY OF BRITISH COLUMBIA January 1988 © Renato Tony Skerl j , 1988 In presenting this thesis in partial fulfilment of the requirements for an advanced degree at the University of British Columbia, I agree that the Library shall make it freely available for reference and study. I further agree that permission for extensive copying of this thesis for scholarly purposes may be granted by the head of my department or by his or her representatives. It is understood that copying or publication of this thesis for financial gain shall not be allowed without my written permission. Department The University of British Columbia 1956 Main Mall Vancouver, Canada V6T 1Y3 DE-6G/81) i i ABSTRACT T h i s t h e s i s descr ibes the synthes is and chemistry of a l k y l 2 ,3-b i s ( t r i m e t h y l s t a n n y l ) - 2 - a l k e n o a t e s ((78) and (83) ) . I t was shown that these compounds cou ld be r e a d i l y transformed i n t o u s e f u l intermediates f o r the s y n t h e s i s o f f u n c t i o n a l i z e d , s te reochemica l l y de f ined te t rasub-s t i t u t e d alkenes (87) and t r i c y c l i c dienes o f genera l s t ruc tu re (322A). The s y n t h e s i s and chemistry of compounds (277) and (278) i s a l s o d e s c r i b e d . The pa l l ad ium(O) -ca ta lyzed a d d i t i o n o f hexamethy ld i t in to a v a r i e t y o f a , ^ - a c e t y l e n i c es te rs (90), a f f o r d e d i n a s t e r e o s e l e c t i v e manner, the corresponding a l k y l ( Z ) - 2 , 3 - b i s ( t r i m e t h y l s t a n n y l ) - 2 -a lkenoates (83) . Subsequent thermolys is of these compounds a f fo rded the cor respond ing a l k y l (E)-2 , 3 - b i s ( t r i m e t h y l s t a n n y l ) - 2 - a l k e n o a t e s (78). I t was found that treatment o f a l k y l (E) - and ( Z ) - 2 , 3 - b i s ( t r i -methy ls tanny l ) -2 -a lkenoa tes wi th methy l l i th ium at low temperature, fo l lowed by r e a c t i o n o f the r e s u l t a n t n u c l e o p h i l i c intermediate wi th a v a r i e t y o f a l k y l a t i n g agents, a f fo rded the t r i s u b s t i t u t e d v iny ls tannanes (80). On the other hand, success ive treatment o f methyl w - h a l o - 2 , 3 - b i s -( t r i m e t h y l s t a n n y l ) - 2 - a l k e n o a t e s (202) wi th methy l l i th ium and HMPA p r o v i d e d a f a c i l e route to c y c l i c / J - t r imethy ls tanny l a ,^ -unsatura ted e s t e r s (203). Compounds (80) were r e a d i l y converted i n t o v i n y l iod ides o f genera l s t r u c t u r e (219) i n which W i s a f u n c t i o n a l i z e d group der ived from the CO2R' moiety. These l a t t e r compounds served as u s e f u l in termedia tes f o r the synthes is o f f u n c t i o n a l i z e d , s te reochemica l ly i i i defined tetrasubstituted alkenes (87). For example, treatment of compounds (219) with 1.1 or 2.2 equiv of n-butyllithium at -78*C afforded the corresponding vinyllithium species (86) , which could either be alkylated directly or further transposed into the organocopper(I) reagent (263A) and then alkylated, to afford i n each case, the tetrasubstituted alkenes (87). The Pd(0)-catalyzed addition of tri-n-butylstannyltrimethylgermane (276) to a variety of a,B-acetylenic esters (90) afforded the corre-sponding compounds (277) and (278) in a ratio of approximately 3:1, respectively. Treatment of the (£) isomers (277) with n-butyllithium at -98°C, followed by alkylation of the resultant nucleophilic intermediate afforded the corresponding trisubstituted vinylgermanes (293). One of these l a t t e r compounds was readily converted into the iodo bromide (308), which is potentially synthetically equivalent to the d,a synthon (310). When the enolate anion of compounds (203) was successively treated with HMPA and compound (308) the esters (311) were obtained. The Pd(0) catalyzed intramolecular coupling of the vinylstannane-vinyl iodide moieties of (311) provided a facile route to the b i c y c l i c triene esters (312). Similarly, alkylation of the enolate anion of compounds (203) with (325) (which was readily obtained from (203), i n which n - 1), followed by the Pd(0)-catalyzed coupling of the resulting alkylated material afforded the t r i c y c l i c diene esters (322A). i v Me3Sn SnMe3 Me3Sn C0 2R' •C02R* H H 90 R C0 2R' R SnMe3 83 78 Me3Sn C0 2R' H R E 80 Me3Sn SnMe3 Me3Sn C02Me C02Me 202 203 I. W E' W LI W Me 2SCu W H >H )H X R E R 87 E 219 R 86 E R E 263A Me3Ge C0 2R' Bu3Sn GeMe3 Q-Bu3SnGeMe, ^ — ^ ^ — ^ 2 7 6 R SnBu3 R C0 2R' 277 278 Me3Ge C0 2Et H Me E 293 308 310 MeO,C Me SnMej I 311 o r Br 325 C0 2Me 322A V TABLE OF CONTENTS Page ABSTRACT i i TABLE OF CONTENTS v LIST OF TABLES v i i i LIST OF FIGURES ix ABBREVIATIONS x ACKNOWLEDGEMENTS x i i INTRODUCTION 1 I. General 1 (a) Transmetalat ion 2 (b) Pa l lad ium(O) -cata lyzed c r o s s - c o u p l i n g 13 II. Previous work and proposals RESULTS AND DISCUSSION 28 I. Prepara t ion of a,B-acetylenic es te rs 28 II . Synthesis of a l k y l (Z)- and ( E ) - 2 , 3 - b i s ( t r i -methylstannyl) -2-a lkenoates and (E) - (N) , (N) -d imethy l -2 ,3 -b is ( t r imethy ls tanny l ) -2 -a lkenamides . . . 33 A . Prepara t ion of a l k y l (Z)- and (E)-2,3-b i s ( t r i m e t h y l s t a n n y l ) - 2 - a l k e n o a t e s 33 B. Spec t ra l data of a l k y l (Z)- and (E ) -2 ,3 -b i s ( t r i m e t h y l s t a n n y l ) - 2 - a l k e n o a t e s 51 v i C. Preparation of (E)-(N),(N)-2,3-bis(trimethylstannyl)-2-alkenamides 66 III . Chemistry of a lkyl (Z) - and (E)-2,3-bis-(trimethylstannyl)-2-alkenoates 71 A. Transmetalation of the t i t l e compounds and reaction of the resultant intermediates with electrophiles 71 B. Synthesis of stereochemically defined trisubstituted v iny l iodides 84 C. Synthesis of functionalized stereochemically defined tetrasubstituted alkenes 109 IV. Synthesis and chemistry of alkyl (E) -2 - ( tr i -n-butylstannyl )- 3 -trimethylgermyl- 2 -alkenoates and a lkyl (Z)-3-(tri-n-butylstannyl)-2-trimethyl-germyl- 2 -alkenoates 123 A. Synthesis of the t i t l e compounds 123 B. Spectral data of alkyl (E)-2-( tr i -n-butyl -stannyl) -2-trimethylgermyl-2-alkenoates and a lkyl (Z)-3-(tri-n-butylstannyl)-2-trimethyl-germyl-2-alkenoates 137 C Chemistry of ethyl (E)-2-(tri-n-butylstannyl)-3-trimethylgermyl-2-butenoate 143 V. Synthesis of b icyc l i c and t r i c y c l i c ring systems . . . 152 VI. Miscellaneous 164 EXPERIMENTAL I. General 166 II . Solvents and Reagents 168 III . Preparation of cr./S-acetylenic esters 169 IV. Synthesis of a lkyl (Z)- and (E)-2 ,3-b is ( tr i -methylstannyl) -2-alkenoates and (E)-N,N-dimethyl-2,3-bis(trimethylstannyl)-2-alkenamides 186 V. Chemistry of a lkyl (Z)- and (E) -2 ,3 -b is ( tr i -methylstannyl) -2-alkenoates 219 v i i VI . Synthesis o f s tereochemica l ly def ined t r i -s u b s t i t u t e d v i n y l iod ides 241 VI I . Synthesis of s tereochemica l ly def ined t e t r a -s u b s t i t u t e d alkenes 259 VI I I . Synthesis and chemistry o f a l k y l ( E ) - 2 - ( t r i - n -bu ty ls tanny l ) -3 - t r imethy lgermy l -2 -a lkenoates and a l k y l ( Z ) - 3 - ( t r i - n - b u t y l s t a n n y l ) - 2 - t r i m e t h y l germyl-2-alkenoates 276 IX. Synthesis of t r i c y c l i c and b i c y c l i c r i n g systems . . . 299 REFERENCES 318 v i i i LIST OF TABLES Table Page I. Conversion of a,^-acetylenic es ters (90) in to a l k y l ( Z ) - 2 , 3 - b i s ( t r i m e t h y l s t a n n y l ) - 2 - a l k e n o a t e s (83) . . . 37 I I . Conversion of a l k y l ( Z ) - 2 , 3 - b i s ( t r i m e t h y l -s tanny l ) -2 -a lkenoates (83) in to a l k y l (E ) -2 ,3 -b i s ( t r i m e t h y l s t a n n y l ) - 2 - a l k e n o a t e s (78) 46 I I I . Se lec ted nmr chemical s h i f t data f o r compounds (78) and (83) 53 IV. Se lec ted ^ C nmr chemical s h i f t data f o r compounds (78) and (83) 57 V. Se lec ted ^ C nmr J values f o r compounds (78) and (83) 59 VI . 1 1 9 S n nmr data fo r compounds (78) and (83) 64 VI I . Conversion of a,B-acetylenic N,N-dimethyl-amides (169) in to ( E ) - ( N ) , ( N ) - 2 , 3 - b i s ( t r i -methylstannyl) -2 -a lkenamides (170) 70 VII I . Transmetalat ion of a l k y l (Z)- or ( E ) - 2 , 3 - b i s -( t r imethy ls tanny l ) -2 -a lkenoates ((183) or (78)) and reac t ions of the r e s u l t a n t intermediates with e l e c t r o p h i l e s 74 IX. Formation of c y c l i c B-trimethylstannyl a,B-unsaturated es ters (203) 83 X. Prepara t ion of v i n y l l i t h i u m species and t h e i r reac t ions with e l e c t r o p h i l e s 112 XI. Prepara t ion of v iny lcopper ( I ) spec ies and t h e i r reac t ions with e l e c t r o p h i l e s 118 XI I . Synthesis o f a l k y l ( E ) - 2 - ( t r i - n - b u t y l s t a n n y l ) -3 - t r imethylgermyl -2 -a lkenoates (277) and a l k y l ( Z ) - 3 - ( t r i - n - b u t y l s t a n n y l ) - 2 - t r i m e t h y l g e r m y l - 2 -alkenoates (278) 131 XII I . Se lec ted nmr data f o r compounds (277) and (278) 138 XIV. Transmetalat ion of e t h y l ( E ) - 2 - ( t r i - n - b u t y l -stannyl ) -3 - t r imethylgermyl -2-butenoate (279) and reac t ions o f the r e s u l t a n t intermediate with e l e c t r o p h i l e s 146 i x LIST OF FIGURES F igure Page 1 The 400 MHz *H nmr spectrum of (137) 54 2 The 400 MHz *H nmr spectrum of (146) 54 3 The 75.6 MHz 1 3 C nmr and APT spect ra of (141) . . . . 61 4 The 75.6 MHz 1 3 C nmr and APT spect ra of (158) . . . . 62 5 The 111.8 MHz 1 1 9 S n nmr spectrum of (141) 65 6 The 111.8 MHz 1 1 9 S n nmr spectrum of (158) 65 7 The 400 MHz lU nmr spectrum of (221) 93 8 The 400 MHz X H nmr spectrum of (258) 114 9 The 400 MHz X H nmr spectrum of (268) 120 10 The 75.6 MHz 1 3 C nmr and APT spect ra of (285) . . . . 141 11 The 75.6 MHz 1 3 C nmr and APT spect ra of (286) . . . . 142 X LIST OF ABBREVIATIONS Ac - a c e t y l AIBN - a z o b i s i s o b u t y r o n i t r i l e APT - attached proton t e s t br - broad Bu - n - b u t y l Biit - t e r t - b u t y l d - doublet DIBAL - di isobutylaluminum hydride DME - 1,2-dime thoxye thane DMF - dimethylformamide DMSO - d imethylsul foxide equiv /eq- equiva lent (s ) Et - e t h y l g - gram(s) g l c - g a s - l i q u i d chromatography h - hour HMPA - hexamethylphosphoric tr iamide i r - i n f r a r e d LDA - l i t h i u m di isopropylamide Me - methyl m - m u l t i p l e t mg - mi l l i gram(s ) MEM - methoxyethoxymethy1 min - minute(s) x i MOM - methoxymethyl mp - melt ing po int mmol - m i l l i m o l e ( s ) ms - mass spectra Ms - methanesulfonyl nmr - nuc lear magnetic resonance nOe - nuclear Overhauser enhancement PCC - pyr id in ium chlorochromate Ph - phenyl PhH - benzene P r 1 - i s o p r o p y l q - quartet s - s i n g l e t t - t r i p l e t TBDMS - t e r t - b u t y l d i m e t h y l s i l o x y T f - t r i f luoromethanesu l fony l THF - te trahydrofuran THP - te trahydropyranyl t i c - t h i n l ayer chromatography TMS - t r i m e t h y l s i l y l Ts - jo- to luenesu l fony l x i i ACKNOWLEDGEMENTS F i r s t l y I would l ike to thank my research supervisor Professor Edward Piers for his guidance and support throughout the course of these studies. Thanks are also extended to the various people associated with the 'group' for useful discussions during those times when things were not moving. I would also l ike to acknowledge the many people, past and pre-sent, for making my stay in Vancouver an enjoyable experience. Special thanks are extended to CITR Radio for providing a breath of fresh a ir during the time spent in the lab. I would also l ike to thank the people associated with various aspects of this thesis. These people include the staff of the nmr and mass spectra labs for the recording of invaluable data. The proofread-ers of this thesis, Montse Llinas Brunet, Rick Friesen, Pierre Marais and Miguel Angel Romero. Greg Statter for the use of his PC, and f i n a l l y Mrs. Rani Theeparajah for her prompt and eff ic ient typing of this manuscript. Financial support from the Department of Chemistry in the form of a teaching assistantship is acknowledged. Thank you and have a nice day. x i i i Mojim Rodi t e l j ima Sta Tude Seres? - 1 -INTRODUCTION I . General A fundamental goal i n organic synthesis i s the e f f i c i e n t and s t e r e o s e l e c t i v e c o n s t r u c t i o n of carbon-carbon bonds. Recent ly , a great deal of a t t e n t i o n has been focused upon the u t i l i t y of s u b s t i t u t e d t r i a l k y l s t a n n y l alkenes for such purposes. ' A p a r t i c u l a r l y a t t r a c t i v e feature inherent i n these compounds i s that they al low the formation of carbon-carbon bonds i n a manner quite d i f f e r e n t from other routes . The use of t r i a l k y l s t a n n y l alkenes for the formation of carbon-carbon bonds may be accomplished by two common r e a c t i o n s . 1) Transmetalat ion^ with an a l k y l l i t h i u m reagent af fords a v i n y l l i t h i u m species which may be trapped with a wide v a r i e t y of e l e c t r o p h i l e s or fur ther transposed, for example, in to an organocopper species which can then be conjugat ive ly added to enones. 2) The pa l lad ium(O)-cata lyzed c r o s s - c o u p l i n g reac-t i o n ^ ' ^ of t r i a l k y l s t a n n y l alkenes with organic e l e c t r o p h i l e s , a r e a c t i o n which t o l e r a t e s a wide v a r i e t y of f u n c t i o n a l groups, c o n s t i -tutes a m i l d method of forming new carbon-carbon bonds. Both o f these react ions proceed with a h igh degree o f s t e r e o s e l e c t i -v i t y . Th i s feature s a t i s f i e s an important p r e r e q u i s i t e necessary i n des igning an e f f i c i e n t synthesis of a complex substrate ( e .g . a n a t u r a l produc t ) . As such, v inylstannanes have become u s e f u l ' t o o l s ' for synthe t i c organic chemists. The two common modes of r e a c t i v i t y that v inyls tannanes undergo, transmeta lat ion and pa l lad ium(O)-cata lyzed c r o s s - c o u p l i n g are discussed i n more d e t a i l i n the fo l l owing sec t ions . - 2 -(a) Transmetalation The transmetalation reaction, which was discovered almost t h i r t y years ago by S e y f e r t h , 3 ' ^ involves a metathesis r e a c t i o n between an organolithium species and an organostannane (or an organic d e r i v a t i v e of another heavy metal) (equation 1). R 3SnR' + R"LI 1 R'Li + R 3Sn R" (1) The r e a c t i o n has been shown to be r e v e r s i b l e , leading to an equilibrium mixture favouring the more stable organolithium species.** Although k i n e t i c studies have been undertaken, the mechanism of transmetalation has not yet been securely established. Nevertheless, the reac t i o n has generally been assumed to proceed through a four-centred t r a n s i t i o n s t a t e ^ (1). Recent studies have provided s o l i d evidence for the existence of hypervalent pentaorgano-tin 'ate' complexes (2) and have implicated them as being intermediates i n the l i t h i u m - t i n exchange.^ However, there has been no evidence to suggest that these 'ate' com-plexes are the actual reactive s p e c i e s , ^ since tests indicate that these 'ate' complexes are s u b s t a n t i a l l y l e s s r e a c t i v e than l i t h i u m reagents toward e l e c t r o p h i l e s such as t r i m e t h y l s i l y l c h l o r i d e and n-butyl iodide. - 3 -The transmetalation reaction is a synthetically viable process for a number of reasons. 1) The reaction usually proceeds ef f ic ient ly at low temperatures, below -50CC. 2) The reaction is completely stereospe-c i f i c . 3) The by-product of the reaction is a coordinatively saturated compound which does not usually interfere with reactions of the l i t h i -ated product. In the case of vinylstannanes, i t is the relative weakness of the tin-carbon bond which allows transmetalation^ to occur. This is in stark contrast to vinylgermanes and vinylsi lanes which are unreactive to alkyl l i thium reagents due to the relative strength of the germanium-carbon and sil icon-carbon bonds. 9 This difference in react iv i ty is c learly exemplified by the synthesis of an intermediate for the Nazarov cycl izat ion (equation 2 ) . ^ Thus, transmetalation of (3) with 3.Ni0 2 ,Et 20 n-butyllithium at -78°C afforded the corresponding vinyl l i thium species, which was allowed to react with 3- or 6-methyl-1-cyclohexenecarbaldehyde to afford the corresponding alcohols. Subsequent oxidation of the lat ter materials afforded the div inyl ketones (4) which underwent the Nazarov cycl izat ion to form the b icyc l i c enones (5). The fact that vinyl l i thium reagents retain the configuration of the organotin precursors was u t i l i z e d by Corey^ in the synthesis of - 4 -11-deoxyprostaglandin E2 (9) (Scheme 1) . The v inylstannane (7) was r e a d i l y prepared by the hydrostannat ion of the terminal acetylene (6). Transmeta lat ion of (7) with n - b u t y l l i t h i u m and convers ion of the r e s u l t i n g v i n y l l i t h i u m species in to a s u i t a b l e cuprate reagent, fo l lowed by r e a c t i o n of the l a t t e r species with 2 - c y c l o p e n t e n - l - o n e , a f forded the conjugate a d d i t i o n product (8) . A fu r ther sequence of steps converted (8) in to the p ros tag land in (9) (Scheme 1) . H- 0-Bu,SnH Bu3Sn OTHP AIBN 1.n-BuLI •OTHP 2 - P r = Cu 3. (CHahCOOH (CH2)4 C H 3 OH OTHP Scheme 1 An e legant use o f f u n c t i o n a l i z e d v inylstannanes was demonstrated by S t i l l ^ i n the synthes is of the germacranolide eucannabinol ide (13). The d e s i r e d cyc lobuteny l t i n reagent (11) was prepared from the k e t a l (10) by a sequence of steps shown i n Scheme 2. Transmetalat ion of (11) wi th n - b u t y l l i t h i u m af forded the corresponding v i n y l l i t h i u m s p e c i e s , - 5 -which, upon treatment with the enone, formed the 1,2-addition product (12) as the major diastereomer. A further sequence of steps converted (12) into the natural product (13) (Scheme 2). Bu3Sn l.BujSnMgCI 0 M e 2.MsCI 3.K2C03,DMSO 1 0 OMe K OMe 11 OMe Ln-BuLI AcO OMe R=PhCH2OCH2 Scheme 2 Vinylstannanes have also been shown to be valuable precursors for the synthesis of polyenes, such as 12-hydroxyeicosa-5,8,14 (Z),10(E) -tetraenoic acid (12-HETE) (18) (Scheme 3 ) . 1 3 Thus, transmetalation of (14) with 1 equivalent of n-butyllithium, followed by treatment of the result ing vinyl l i thium species with a suspension of n-Bu^NCu(CN)2 and coupling of the resultant reagent with a functionalized alkyl iodide, afforded the vinylstannane (15). Sequential treatment of (15) with - 6 -n-butyllithium and cuprous bromide•dimethylsulphide complex afforded an organocopper reagent, which was treated with the acetylenic ketone (16). The resultant intermediate was quenched with a protic source to afford the corresponding conjugate addition product (17). A further sequence of steps converted (17) into the polyene 12-HETE (18). 4.HOAc,MeOH Scheme 3 The scope of the transmetalation reaction is further i l lus trated by the stereocontrolled construction of the C(3)-C(17) fragment of a-plasmomycin, a boron-containing antibiot ic (equation 3 ) . ^ Thus, reaction of (19) with n-butyllithium produced the corresponding vinyl l i thium species, which was sequentially treated with cuprous cyanide and the epoxide (20) to afford the coupled product (21). - 7 -Bu 3 Sn The retention of stereochemistry in the transmetalation of v i n y l -stannanes has been used in the short synthesis of the marine metabolite ( ± ) - t r i o p h a m i n e (25) (Scheme 4 ) . 1 5 This work established the configuration of the o lef inic double bonds present in the natural product. Thus, transmetalation of (E)-3-(tri-n-butylstannyl)-2-pentene Scheme 4 - 8 -(22) with n-butyllithium, followed by conjugate addition of the resultant vinyl l i thium species to (23), provided the o lef inic trimethyl-hydrazide (24). A further sequence of steps converted (24) into the natural product (25) . When a similar sequence of steps (Scheme 4) was repeated with (Z)-3-(tri-n-butylstannyl)-2-pentene a material different from the natural product was obtained.^ Recently a vinylstannane has been exploited for the stereoselective synthesis of a tetrasubstituted alkene (Scheme 5 ) . ^ a Thus, treatment of (26)16^ with n-butyllithium chemoselectively afforded a vinyl l i thium species, which was transformed into the corresponding organocopper derivative. The latter species was coupled with a l l y l bromide to form the trisubstituted vinylstannane (27). Halogen-metal exchange of (27) gave the corresponding v iny l iodide, which, upon treatment with tert-butyll ithium, afforded the vinyl l i thium (28). This reagent was converted into an organocopper derivative which was coupled with methyl iodide to afford the tetrasubstituted alkene (29). Hex Hex 1.n-BuLI Et 2B 26 2.CuBr>Me2S SnMe3 3.CH2CHCH2Br SnMe3 27 2.t-BuLi Hex Hex Me HMPA,P(OEt)3 2.Mel 1.CuBr>Me,S LI 29 28 Scheme 5 - 9 -The vinylstannane (26) can be regarded as a bifunctional conjunctive reagent .^ By d e f i n i t i o n ^ such a reagent possesses two reactive sites (e.g. two donor centres, two acceptor centres, or one donor and one acceptor centre) and is incorporated in whole or in part into a sub-strate molecule. A donor (d) centre refers to a potential nucleophilic centre, whereas an acceptor (a) centre refers to a potential electro-p h i l i c c e n t r e . ^ Hence (26) is synthetically equivalent to the d,d synthon* (30), in which the two donor centres are c is -re lated. H e x The v e r s a t i l i t y of vinylstannanes has recently been highlighted by the stereoselective synthesis of substituted enynes, dienes and alkenes v ia the stannylation of 1-trimethy1silyl 1 ,3-diynes.^ Thus, upon treatment of (31) with trimethylstannylcopper-dimethyl s u l f i d e ^ (2.5 equiv) in THF the corresponding (E)-bis(trimethylstannyl) enynes (32) were obtained in a chemo- and stereoselective fashion. These latter materials were then further elaborated into stereodefined tetrasubsti-tuted enynes (35). Addition of 1 equiv of methyllithium to a solution of (32) in THF afforded, chemoselectively, the corresponding v i n y l l i t h -ium species, which were trapped with an appropriate electrophile to form the trisubstituted vinylstannanes (34). A further sequence of steps A synthon is a unit within a molecule which can be synthesized, modified or joined by known or conceivable synthetic operations.^ 9 - 10 -involving transmetalation-alkylation of (34) afforded the. tetrasubsti-tuted enynes (35) (Scheme 6). Compounds (32) are thus synthetically equivalent to the d,d synthons (33) in which the two donor centres are trans-related. Scheme 6 In the preceeding discussion, two examples portraying bifunctional conjunctive reagents possessing two donor centres were presented. Attention now w i l l be focussed on examples of bifunctional conjunctive reagents possessing a donor carbon atom and an acceptor carbon atom. Reagents corresponding to such synthons constitute useful species for annulation reactions.^2 xhe required precursors of the reagents w-substituted 2-trimethylstannyl-l-alkenes (37) can be readily prepared by the addition of trimethylstannylcopper'dimethyl sulfide to w-substi-- 11 -tuted 1-alkynes (36) at - 6 3 ° C i n the presence of methanol (equation 4).2 3 The substances (37) are p o t e n t i a l l y s y n t h e t i c a l l y equivalent to the d,a synthons (38). SnMe, _ _ _ _ _ MejSnCu-MejS.tf eq) / d " = = l*' M 2)n — < • • (41 Nx MeOH(60 eq),-63°C \ \ 1 ' 36 37 ( C H 2 ) n ~ X 38 The u t i l i t y of compounds of general structure (37) i s c l e a r l y exemplified by the development of an e f f i c i e n t methylenecyclopentane annulation p r o c e s s ^ a which was used i n the t o t a l synthesis of (±)-A 9^ 1 2)-capnellene (42) (Scheme 7 ) . 2 ^ Thus, transmetalation of (39) Scheme 7 - 12 -afforded the corresponding vinyl l i thium species, which was treated with magnesium bromide to form the corresponding Grignard reagent. Copper(I)-catalyzed addition of the latter reagent to 2-methyl-2-cyclopenten-1-one in the presence of boron tr i f luor ide etherate afforded the conjugate addition product (40). Treatment of (40) with potassium hydride in THF afforded the b i cyc l i c ketone (41), which, v ia a further sequence of steps, was converted into ( ± ) - A 9 ( 1 2 ) - c a p n e l l e n e (42). Recently, a total synthesis of the sesterterpenoid ( ± ) - p a l a u o l i d e (46) (Scheme 8)25 was achieved u t i l i z i n g a methylenecyclohexane ambula-tion process,^2b which had been developed using reagents corresponding Scheme 8 - 13 -to d , a synthons s i m i l a r to those d iscussed above. Thus, fo l l owing a sequence of steps e n t i r e l y analogous to those d iscussed above (Scheme 7) , the Grignard reagent der ived from the v inyls tannane (43) was added c o n j u g a t i v e l y to 3 ,6-d imethyl -2 -cyc lohexen- l -one , to a f f o r d the chloro ketone (44). Treatment of the l a t t e r substance wi th potassium t e r t -butoxide i n t e r t - b u t a n o l . a f forded the b i c y c l i c ketone (45), which v i a a f u r t h e r sequence of s teps , was converted in to ( ± ) - p a l a u o l i d e (46).^5 (b) Palladium(O') - ca ta lyzed c r o s s - c o u p l i n g One of the most v e r s a t i l e react ions to have emerged i n the past few years has been the pa l lad ium(O)-cata lyzed c r o s s - c o u p l i n g r e a c t i o n of organot in reagents with organic e l e c t r o p h i l e s . ^ • ^ This r e a c t i o n takes p lace under m i l d c o n d i t i o n s , t o l e r a t e s a wide v a r i e t y of f u n c t i o n a l groups on e i t h e r coupl ing par tner , i s s t e r e o s p e c i f i c and genera l ly gives h igh y i e l d s o f product . Although other organometal l ic reagents con-t a i n i n g metals of intermediate e l e c t r o p o s i t i v e character ( e .g . Zn, B, A l , Hg)^ D undergo pa l lad ium(O)-cata lyzed c r o s s - c o u p l i n g react ions with organic e l e c t r o p h i l e s , organostannanes have been the most widely used. Presumably, organostannanes are p a r t i c u l a r l y u s e f u l because they are r e l a t i v e l y easy to prepare and are s tab le towards moisture and oxy-g e n . 2 7 a In the pa l lad ium(O)-ca ta lyzed c r o s s - c o u p l i n g of e l e c t r o p h i l e s with organot in reagents , only one of the groups on t i n enters in to the coup l ing r e a c t i o n (equation 5) . Furthermore, d i f f e r e n t groups are - 14 -RX + R"SnR'3 " R- R' + XSnR'3 (5) transferred from t i n with different rates. For example, simple a lkyl o groups (e.g. methyl or butyl) exhibit the slowest transfer rate. Thus, an unsymmetrical organotin reagent containing three simple a lkyl groups and a fourth functionalized group (e.g. alkynyl, alkenyl, a r y l , benzyl or a l l y l ) w i l l transfer, exclusively, the latter group. Functionalized vinylstannanes undergo the palladium(O)-catalyzed cross-coupling reaction with a variety of electrophiles: v iny l halides, 2** v iny l t r i f l a t e s , 2 7 a c i d c h l o r i d e s , 2 9 a l l y l h a l i d e s , 3 u aryl t r i f l a t e s , 3 ^ and aryl h a l i d e s . 3 2 The pathway v ia which the pal la -dium^) -catalyzed cross-coupling reaction is thought to occur is i l lus tra ted by the catalyt ic cycle shown in Scheme 9. The i n i t i a l step in the reaction can be considered to be oxidative addition of the electrophile to a palladium complex 'PdL,2'. The subsequent steps are transmetalation, trans/cis isomerization and reductive elimination, affording the coupled product R-R' and the palladium complex 'PdT_2'. The most commonly used palladium catalyst is tetrakis(triphenylphos-phine)palladium(O) (Pd(PPh 3 ) 4 ). The high stereoselectivity and the tolerance of functional groups in the cross-coupling reaction is i l lus trated by the synthesis of the insect pheromone (49) (equation 6 ) . 2 ® Thus, in a single step the v i n y l -stannane (47) was coupled with the v iny l iodide (48) to afford the pheromone (49). This reaction proceeded without any isomerization of the o le f in ic double bonds and without protection of the alcohol moiety. - 15 -Bu 4 7 4 8 4 9 The u t i l i t y of the palladium(O)-catalyzed cross-coupling reaction is further i l lus trated by the synthesis of a key intermediate in the synthesis of the antibiot ic ( ± ) - p y r e n o p h o r i n (53) (Scheme 1 0 ) . 2 9 a > 3 3 Thus, the acid chloride (50) was coupled with the vinylstannane (51) to afford the ketone (52), which was subsequently elaborated into the antibiot ic (53). The coupling reaction proceeded in the presence of the ester group and with retention of double-bond configuration. - 16 -Scheme 10 A further example i l lu s t ra t ing that a wide variety of functional groups can be tolerated in the coupling process is shown in equation 7. Reaction of the functionalized a l l y l bromide (54) with the v inyl stannane (55) proceeded smoothly to afford the coupled product (56). In part icular , this reaction exhibits regioselective carbon-carbon bond formation since the a l l y l halide (54) undergoes coupling at the less substituted carbon of the a l l y l i c framework. - 17 -One of the more versati le coupling processes involves the reaction of vinylstannanes with v iny l t r i f l a t e s , since the latter substances can be obtained readily from ketones3^ in a regioselective manner u t i l i z i n g well known enolate chemistry. This type of transformation was demon-strated in a synthesis of p leraplys i l l in -1 (60) (Scheme l l ) . 2 7 b The t r i f l a t e (58) was prepared as one regioisomer from 5,5-dimethyl-2-cyclo-hexen-l-one (57) by conjugate reduction u t i l i z i n g L - S e l e c t r i d e , ® followed by trapping of the enolate with N-phenyltrifluoromethylsulfon-imide. Palladium(O)-catalyzed coupling of (58) with the vinylstannane (59) proceeded smoothly in the presence of lithium chloride to afford p l erap lys i l l in -1 (60). Scheme 11 Recently, an annulation method leading to diene systems3-* has been developed u t i l i z i n g intramolecular palladium(O)-catalyzed cyclizations of enol triflate-vinylstannanes (equation 8). For example, transforma-- 18 -n = 1 o r 2 t ion of the ketones (61) into the corresponding enol t r i f la tes (62) was accomplished by u t i l i z i n g the procedure of McMurry and Scott . 3 ^ Treatment of compounds (62) with a catalyt ic amount of (PPt^^Pd effected eff ic ient ring closure to produce the b icyc l i c dienes (63). A variant of the annulation method described above that produces products in which both double bonds of the diene system are endocyclic has been developed3** and applied to the total synthesis of ( ± ) - ( 1 4 S ) -dolasta-l(15),7,9-trien-14-ol (67) (Scheme 1 2 ) . 3 6 Thus, the enolate of the ketone (64) was formed under thermodynamically controlled conditions and alkylated with (Z)-l-bromo-4-methyl-3-trimethylstannyl-2-pentene to afford the corresponding ketone (65). The latter material was treated with lithium diisopropylamide affording the enolate anion, which was trapped with N_-phenyltrifluoromethylsulfonimide producing the corre-sponding enol t r i f l a t e . Direct addition of a catalyt ic amount of (PPlvj^Pd to the solution containing the latter material provided the ketal diene (66). A further sequence of steps converted (66) into the - 19 -Scheme 12 natural product ( ± ) - ( 6 7 ) . S t i l l e 3 ^ recently demonstrated that the intramolecular palladium(O)-catalyzed cyclizations of v iny l triflate-vinylstannanes can be used for the synthesis of large-ring lactones (equation 9). The reactions were 68 69 performed under high di lut ion (10"* M) conditions in refluxing THF to afford the lactones (69) in isolated yields of 56-57%. Under the mild - 20 -reaction conditions, no E to Z isomerization of the E alkene function and no rearrangement of the exocyclic double bond occurred. Although the chemical l i terature contains numerous examples i l l u s -trating the u t i l i t y of the palladium(O)-catalyzed cross-coupling reac-t ion, the examples discussed in the preceeding text serve to i l lus tra te the relat ive ease with which two sp 2 carbon centres can be brought together with the formation of a new carbon-carbon bond. II . Previous work and proposals Previous work in our laboratories had focussed on the reaction of various (trimethylstannyl)copper(I) reagents with a,8-acetylenic esters . 3 ^ It was shown that the conjugate addition of two of these reagents to a,3-acetylenic esters (e.g. ethyl 2-butynoate) (70) could be controlled experimentally so as to produce, stereoselectively, either of the geometrically isomeric products (71) (the product of kinetic control) or (72) (the product of thermodynamic control) (Scheme IS). 3** 3 Me C0 2Et Me H Me3Sn H + 70 71 Me3Sn 72 C0 2Et (Me3SnCuSPh)LI , - 48°C,THF 2 Me3SnCu»Me2S , -48°C,THF > 99 < 1 98 Scheme 13 - 21 -Thus, reaction of (70) with lithium (phenylthio)(trimethylstannyl)-cuprate (THF, - 4 8 ° C ) , followed by protonation, produced the (Z) isomer (72) (>98% isomerically pure). On the other hand, reaction of (70) with (trimethylstannyl)copper(I)•dimethylsulfide (THF, - 4 8 ° C ) , followed by protonation, produced the (E) isomer (71) (>99% isomerically pure). At the time the preceeding study was done i t was envisaged that the synthetic u t i l i t y of the methodology described above could be enhanced s igni f icant ly i f the presumed intermediates (73) and/or (74) could be trapped with electrophiles ("E+") other than proton to afford the corresponding products (75) and/or (76) (Scheme 15). However, attempts to trap (73) and/or (74) with electrophiles (e.g. methyl iodide, benzyl bromide or cyclohexanone) fa i l ed . In each case, appropriate workup gave Me C0 2Et Cu — | Me 3Sn C0 2Et Me 3Sn Me 3Sn Me 73 E C0 2Et Me 3Sn E 75 76 Scheme 15 The formulas (73) and (74) are not meant to imply actual structures, but are used for the sake of c l a r i t y . - 22 -only the product resulting from protonation of the intermediates. In efforts to f ind conditions under which the desired trapping reactions would take place, the reaction temperature was increased. However, when methyl iodide was added to the reaction mixture obtained by allowing (70) to react with (trimethylstannyl)copper(I)•dimethylsulfide and the temperature was allowed to r ise from -48° to 0°C, the material obtained upon workup contained none of the desired product (76) (E = CH3). Instead, there was obtained, in addition to (76) (E=H), a low y i e ld of a substance which contained two trimethylstannyl groups and which was subsequently identif ied as ethyl (E)-2,3-bis(trimethylstannyl)-2-butenoate (77). Compound (77) represented a novel type of organotin derivative. After some experimentation i t was found that when (70) was allowed to react (THF, -48°C, 30 min, 0°C, 3 h) with 2.5 equiv of (trimethylstan-nyl) -dimethyl sulfide, the ester ethyl (E)-2,3-bis(trimethylstannyl)-2-butenoate (77) was produced in good y ie ld (equation 10).^1 Me — C0 2Et M» 3SnCu.Me 2S \ = J 2.5 eq, THF / \ Me3Sr\ C02Et (10) 7 0 7 7 Interestingly, the ct-Me3Sn group of ethyl (E)-2, 3-bis (trimethyl-stannyl)-2-butenoate (77) could be removed direct ly and selectively by transmetalation with methyllithium, without interference from either the ester moiety or the B-tte^Sn group. Furthermore, i t was found that the resultant nucleophilic intermediate reacted with a variety of reactive - 23 -electrophiles to afford trisubstituted vinylstannanes (75) (equation 11) . 2 ^ It has been postulated that the intermediate resulting from the Me3Sn C0 2Et Me3Sn C0 2Et 1 .MeLl.THF Me SnMe3 Me E 77 75 transmetalation of an a,/?-bis(trimethylstannyl) aunsaturated ester such as (77) with methyllithium is an allenoate a n i o n 3 9 (79), which reacts with an electrophile to give only one stereoisomer (80) (equation 12) . In fact, Marino^ has reported evidence that indicates that an allenoate intermediate may be involved in the addition of lithium dimethylcuprate to methyl propynoate. Me3Srt C02R' Me3Sn OR' Me3Sn C02R' >=< ( 1 2 ) R SnMe3 R OLI R E 78 79 80 One of our i n i t i a l goals was to investigate the poss ib i l i ty of preparing a lkyl 2,3-bis(trimethylstannyl)-2-alkenoates v ia an alterna-tive route. An alternative was desirable for a number of pract ica l reasons. 1) In the previous synthesis of a lkyl (E)-2,3-bis(trimethyl-stannyl) -2-alkenoates 2.5 equivalents of (trimethylstannyl)copper(I)• dimethyl sulf ide, and, therefore, 2.5 equivalents of hexamethylditin are required to form 1 equivalent of the desired product (equation 10). This is an important point since the price of hexamethylditin is >$3.00 per gram. 2) Copper(I) reagents are very sensitive to moisture, oxygen - 24 -and traces of inorganic s a l t s , ^ and, therefore, reactions involving these reagents can be capricious. 3) The reagents that are required for the formation of (trimethylstannyl)copper(I)• dimethyl sulfide, methyl-lithium and copper(I) bromide'dimethyl sulfide, tend to lose their ac t iv i ty after a short period of time. Thus, i t is important that both of these reagents are either freshly prepared (in the case of CuBr.Me2S), or, taken from a freshly opened bottle^*2 ( i n the case of methyllithium). Furthermore, the (trimethylstannyl)copper(I) reagents are thermally unstable, therefore, i t is necessary to carry out the reactions at low temperatures. Mitchel l ,^* 3 3 has reported the preparation of (Z)-1,2-bis(trimethyl-stannyl)-1-alkenes (82) by a novel route. Treatment of 1-alkynes (81) with hexamethylditin in the presence of a catalyt ic amount of (PPh^^Pd afforded (82) in a stereoselective manner (equation 1 3 ) . I s o l a t e d Me 3 Sn SnMe 3 H • H M e 6 S n 2 y = / (i3) Pd(pph3)4 8 1 ~ R 8 2 " yields of (82) ranged from 29% (R-C4H9) to 80% (R-H). The generality of the reaction was not investigated thoroughly, but i t was found to proceed for 1-alkynes in which R-Ph, MeOCH2 or PhCT^. However, efforts to extend the palladium(O)-catalyzed addition of hexamethylditin to non-terminal acetylenes were not successful. Nevertheless, we fe l t that i t would be worthwhile to investigate the poss ib i l i ty of preparing a lkyl 2,3-bis(trimethylstannyl)-2-alkenoates by the Pd(0)-catalyzed addition of hexamethylditin to a,B-acetylenic esters. - 25 -In the general introduction, the two common types of reaction that vinylstannanes undergo, transmetalation and palladium(O)-catalyzed cross-coupling, were shown to be highly versati le and depending on the part icular reaction, were shown to be chemo-, regio- and/or stereo-selective. Thus, i t was of particular interest to investigate the chemistry of 2,3-bis(trimethylstannyl)-2-alkenoates to determine whether or not they could be used effectively in synthesis. For example, i t appeared to us that either the (Z) or (E) esters ((83), (78), respect-ively) could serve as precursors for a fac i le route to functionalized, stereochemically defined tetrasubstituted alkenes (84) or (87), (Scheme 16). Thus, transmetalation of either the (E) isomer (78) or the (Z) isomer (83) , would presumably afford the same allenoate anion intermediate (79) , which could be trapped with a variety of electro-philes to afford the corresponding trisubstituted vinylstannanes (80). Suitable manipulation of the ester group of (80) would provide compounds of general structure (85) (W is a functionalized group derived from the CO2R' moiety). These latter compounds could serve as effective synthetic equivalents of the synthons (88). For example, i t was envisaged that reagents (86) , presumably available by transmetalation of (85), could be trapped by a variety of electrophiles to afford the corresponding tetrasubstituted alkenes (87). Alternatively, the fu l ly substituted alkenes (84) could be prepared from the palladium(O)-catalyzed cross-coupling reaction of the vinylstannanes (85) with an organic electrophile (e.g. v iny l halide, a l l y l halide or v iny l t r i -f la te ) . I f the plans outlined in Scheme 16 proved to be successful, then the synthesis of functionalized, stereochemically defined tetra-- 26 -Me3Sn SnMe3 Me3Sn OR' Me3Sn C02R' H — > — ( — H R 8 3 C02R' R ? g OLI R ^ SnMe 3 Me3Sn C02R' H Scheme 16 substituted alkenes would have been accomplished. It may be noted that, up to the present time, methodologies leading to such alkenes have been s c a r c e . 1 6 - 2 0 . 4 4 If the palladium(O)-catalyzed addition of hexamethylditin to a,8-acetylenic esters proved to be a viable route for the preparation of - 27 -2,3-bis(trimethylstannyl)-2-alkenoates, then a further poss ib i l i ty could be explored. In part icular, we were interested in effecting the palladium(O)-catalyzed addition of 'mixed' bimetall ic reagents ( u t i l i z -ing other Group IV elements such as s i l i con and germanium, for example, Me3SnSiMe3^ to a,^-unsaturated esters. The following chapters discuss the progress made thus far in this area of research. - 28 -RESULTS AND DISCUSSION I . Preparat ion of a,y9-acetylenic esters The r e q u i s i t e a , 8 - a c e t y l e n i c esters were prepared v i a known m e t h o d s . 4 2 In genera l , these mater ia l s were prepared by the r e a c t i o n of a l k y n y l l i t h i u m reagents (89) with methyl or e t h y l chloroformate (equation 15). Some of the r e q u i r e d a l k y n y l l i t h i u m species were, i n t u r n , generated by deprotonation of the corresponding 1-alkynes (81) with m e t h y l l i t h i u m 4 7 (equation 14). In general , the 1-alkynes (81) were e i t h e r commercial ly a v a i l a b l e or were made v i a known m e t h o d s . 4 2 R H+ MeLI R L I + CH 4 ( 1 4 ) 81 89 R — — u + ciccyr R — = = = — c c - j R 1 + L I C I ( 1 5 ) 89 90 The a l k y n y l l i t h i u m reagents requ ired for the prepara t ion of some w - h a l o - a , ^ - a c e t y l e n i c es ters were generated by the r e a c t i o n o f n - b u t y l -l i t h i u m with 1,1-dibromo olefins. 4 * 3 " For example, the 1,1-dibromo o l e f i n (94) served as an intermediate for the preparat ion of methyl 8-bromo-2-octynoate (95) (Scheme 17). Thus, treatment o f the commercially a v a i l a b l e d i o l (91) with hydrogen bromide (48%) i n r e f l u x i n g benzene 4 9 af forded (g lc a n a l y s i s ) , a 10:1 mixture of the monobromo product (92) and the corresponding dibromo product , r e s p e c t i v e l y . Column chromato-graphy of the crude mixture of these l a t t e r two mater ia l s on s i l i c a ge l a f forded 70% of the des i red product (92). Oxidat ion of the l a t t e r - 29 -Scheme 17 substance with pyridinium chlorochrornate3 afforded the aldehyde (93), which was treated with Ph3P=CBr2 (prepared from carbon tetrabromide, triphenylphosphine and Zn d u s t 4 ® ) to afford, in 96% y ie ld , the corresponding tribromide (94). This latter material, upon successive treatment with a solution of n-butyllithium in hexane and methyl chloroformate afforded, in 89% y ie ld , methyl 8-bromo-2-octynoate (95). In a sequence of steps entirely analogous to those depicted in Scheme 17, the alcohol 6-chloro-l-hexanol was transformed into the a,B-acetylenic ester methyl 8-chloro-2-octynoate (98) in an overall y i e ld of 65%. Once a particular co-halo a,/J-acetylenic ester had been prepared, i t could be converted conveniently into a structurally related substance by synthetically manipulating the halide moiety. For example the iodide (99) was readily prepared in 93% y ie ld from the bromide (95) by u t i l i z -We thank Professor L . Weiler for a generous sample of this compound. - 30 -Nal C02Me (CH3)2CO C02Me (16) ing the Finkelstein reaction (equation 16). By u t i l i z i n g the same reaction the chloride (100) was converted into the iodide, methyl 6-iodo-2-hexynoate (102), in 91% y i e l d . On the other hand, the bromide (101) could be prepared from the corresponding chloride (100) by u t i l i z i n g phase transfer catalysis.-'I Thus, successive treatment of a solution of (100) in heptane with a mixture of sodium bromide, water and Adogen 464® afforded the bromide (101) in 72% y ie ld (equation 17). NaBr, H,0 Adogen 464® ^ \ (17) 1 o1 C02Me A substitution reaction was also u t i l i z e d in the preparation of the bromide (104) (equation 18). The requisite j>-toluenesulfonate (1-03) was prepared by treating a solution of ethyl 5-hydroxy-2-pentynoate in CH2CI2 with j> -toluenesulfonyl chloride in the presence of pyridine and 4-dimethylaminopyridine. Subsequent treatment of a solution of the TsO NaBr,DMF Br (18) 104 C0 2Et We thank Mr. J . Wai for a generous sample of this compound. - 31 -E-toluenesulfonate (103) in DMF with sodium bromide afforded (90%) the corresponding bromide (104). Another type of a,B-acetylenic ester that was required was a that treatment of a terminal acetylene in the presence of an internal t r i p l e bond with B-bromo-9-borabicyclo[3.3.l]nonane afforded the corre-sponding v iny l bromide in a regio- and chemoselective manner. Such haloboration reactions proceed through cis addition of the reagent to terminal acetylenic bonds only, with the bromine and the boron moiety becoming attached to C-2 and C - l , respectively. Protonolysis of the intermediate affords exclusively the 2-bromo-l-alkene. Hence we envisaged u t i l i z i n g the haloboration reaction for the preparation of the ct,^-acetylenic ester, methyl 8-bromonon-8-en-2-ynoate (108) (Scheme 18). We fe l t that a suitable substrate for the haloboration reaction was the diynoate (106) , which could be obtained readily from the commercially available diyne (105). Thus, successive treatment of a THF functionalized enyne. Suzuki,- ) Z in a remarkable reaction, had shown C02Me C02Me 1 .MeLl.THF 2.CIC02Me 1 05 Br Scheme 18 - 32 -solution of the lat ter material with a solution of methyllithium (1.3 equiv) in ether and methyl chloroformate afforded (glc analysis), approximately a 1:1 mixture of the monoester (106) and the diester (107). Tic analysis showed that the mobilities of the two esters were very different and, therefore, these two substances were readily separated by column chromatography on s i l i c a gel . The required monoester (106) was isolated in 40% y ie ld . Subsequent treatment of a solution of the latter material in C H 2 C I 2 with B-bromo-9-borabicyclo-[3.3.1]nonane afforded (87%) the bromide (108). Since i t is possible to effect the mono-hydrogenationJ-> of a 1-alkyne function in the presence of an internal t r ip le bond, we fe l t that a diynoate such as (109) could also serve as an effective precursor to an enyne. The particular enyne that was required was methyl 6-hepten-2-ynoate (111) (equation 19). The requisite diynoate (109) was ,C02Me ( 1 9 ) ^/^S^ Pd -BaSQ 4 ,H 2 ^ Hexane 109 111 readily prepared (36% yield) by successive treatment of a THF solution of commercially available 1,5-hexadiyne with a solution of methyllithium in ether and methyl chloroformate. Subsequent hydrogenation of a solution of (109) in hexane in the presence of 10% palladium-on-barium sulfate afforded, after a reaction time of 2 h, the corresponding enyne(111) in an isolated y ie ld of 73%. It should be noted that each of the a,B-acetylenic esters discussed in this section exhibited spectral data in f u l l accord with the assigned - 33 -structure (see Experimental Section). Some of the a,/9-acetylenic esters that were employed in the work described in this thesis were prepared by known methods. 4 2 These a,B-acetylenic esters include ethyl 2-butynoate (70), methyl 2-pentynoate (114), methyl 4-methyl-2-pentynoate (115) and ethyl 4-tert-butyldimethvl-siloxy-2-butynoate (116). On the other hand, some of the a ,B-acetylenic esters were obtained from other researchers in our laboratory, who had prepared them by u t i l i z i n g known methods. 4 2 These a,B-acetylenic esters include methyl 3-cyclopropyl-2-propynoate (117), methyl 7-tert-butyl-dimethylsiloxy-2-heptynoate (118), methyl 6-tetrahydropyranyloxy-2-hexy-noate (119), methyl 5-(2-cyclopentenyl)-2-pentynoate (120), methyl 4-(3-cyclohexenyl)-2-butynoate (121), ethyl 5-chloro-2-pentynoate (122)-*4 and methyl 7-bromo-2-heptynoate (123). II . Synthesis of a lkyl (Z)- and (E)-2,3-bis(trimethylstannyl)-2-alkenoates and (E)-N,N-dimethyl-2,3-bis(trimethylstannyl)-2-alkenamides A. Preparation of a lkvl (Z)- and (E)-2.3-bis(trimethylstannyl)-2- alkenoates In the general introduction of this thesis i t was mentioned that our i n i t i a l objective was to explore the poss ib i l i ty of preparing a lkyl 2,3-bis(trimethylstannyl)-2-alkenoates v ia a route different from that employed previously in our laboratory u t i l i z i n g organocopper(I) - 34 -reagents.21 In doing so we hoped to overcome some of the pract ical problems associated with using organocopper(I) reagents. These problems were mentioned in the general introduction. M i t c h e l l ^ 3 a had reported the preparation of (2)-1,2-bis(trimethylstannyl)-1-alkenes by the palladium(O)-catalyzed addition of hexamethylditin to 1-alkynes. Thus, we sought to investigate the poss ib i l i ty of adding hexamethylditin to a,8-acetylenic esters, u t i l i z i n g palladium(O) catalysis . In the f i r s t such effort directed towards probing the poss ib i l i ty of adding hexamethylditin to an a,B-acetylenic ester u t i l i z i n g palladium(O) catalysis , the following reaction was attempted. To a solution of ethyl 2-butynoate (70) in THF was added 1 equivalent of hexamethylditin and 0.01 equivalents of (PPl^^Pd. After the reaction mixture had been s t i rred at room temperature for 21 h glc analysis of an aliquot indi -cated the absence of a peak corresponding to ethyl 2-butynoate (70) and the appearance of another major peak. Tic analysis ( s i l i c a gel, development with 95:5 petroleum ether-diethyl ether) of the mixture indicated the presence of one major component (Rf - 0.11) and a minor component (Rf - 0.90) corresponding to hexamethylditin. Removal of the solvent, followed by column chromatography of the residual orange-red o i l on s i l i c a gel and d i s t i l l a t i o n ( 7 0 - 7 5 ° C / 0 . 1 Torr) of the o i l thus obtained, afforded 82% of a clear, colorless o i l . This material was subsequently identif ied as ethyl (Z)-2,3-bis(trimethylstannyl)-2-butenoate (124) from an analysis of i t s spectral data ( i r , ms, ^H nmr). Structural elucidation of (124) was also fac i l i ta ted by comparing i t s chromatographic behaviour and spectral data with those of an authentic sample of ethyl (E)-2,3-bis(trimethylstannyl)-2-butenoate (77). This - 35 -Me3Sn H SnMe3 Me3Sn C02Et Me C02Et H Me SnMe3 124 77 lat ter material had been prepared by the addition of trimethylstannyl-copper(I)•dimethyl sulfide complex to ethyl 2-butynoate ( 7 0 ) . 2 1 Chromatographically, the two geometric Isomers (124) and (77), showed different behaviour. For example, t i c analysis ( s i l i c a gel, development with 95:5 petroleum ether-diethyl ether) showed that the (Z) isomer (124) (Rf - 0.11) was more polar than the (E) isomer (77) (Rf = 0.32). Furthermore, glc analysis of a pure sample of the (E) isomer (77) indicated that i t was thermally stable since a clean chromatogram with one dis t inct component was obtained. On the other hand, glc analysis of a pure sample of the (Z) is omer (124) indicated that i t was thermally unstable since a chromatogram with one major component and several unidentified components was obtained. The nmr and i r spectra of the (Z) isomer (124) were readily interpreted and they showed some dist inct differences from the corre-sponding spectra of the (E) isomer (77). For example, the infrared spectrum of the (Z) isomer (124) showed an absorption at 1700 cm"1, attributable to the carbonyl stretching frequency of the a,^-unsaturated ester moiety, and an absorption at 775 cm*1 due to the tin-methyl rocking frequency of a trimethylstannyl group. In contrast, the i r spectrum of the (E) isomer exhibited a carbonyl absorption at 1685 cm"1. The -^H nmr spectrum of the (Z) isomer (124) consisted of two sharp 9-proton singlets at S 0.22 (2J_sn-H = 5 2 , 5 H z ^ a n d 6 0 , 2 5 <2j-Sn-H = - 36 -53.5 Hz), a 3-proton t r ip l e t at S 1.27 (J - 7 Hz), a 3-proton singlet at 6 2.07 (^J.Sn-H - 10 Hz, ^Isn-H ~ ^ **z) a n c * a 2-proton quartet at 5 4.15 (J «= 7 Hz). In comparison, the ^H nmr spectrum of the (E) isomer (77) exhibited 9-proton singlets at 6 0.14 (2J.Sn-H " 5 3 H z ) a n d S 0 , 2 5 ( 2 J S n . H - 54 Hz), and a 3-proton singlet at S 2.22 ( 4 J.s n -H " 1 1 H z> 3 J g n _ L j - 49 Hz). In addition to the above spectral data, high resolution mass spectrometry showed that the molecular formula for the (Z) isomer (124) was C 1 2 H 2 6 ° 2 S n 2 -As a consequence of the eff ic ient , fac i le palladium(O)-catalyzed addition of hexamethylditin to ethyl 2-butynoate (70), we decided to investigate the generality of this reaction u t i l i z i n g a variety of a,/9-acetylenic esters. As such, the compounds of general structure (83) l i s t ed in Table I were prepared in isolated yields ranging from 64% to 95%. It is pertinent to note that many of the yields l i s t ed in Table I have not been optimized. Although the reactions were i n i t i a l l y per-formed at room temperature (entries 2-6), i t was found that reaction times were decreased when the reactions were carried out in refluxing THF. In each case (Table I) the progress of the reaction was easily monitored by t i c and/or glc analyses. A variety of functional groups present in the a,6-acetylenic esters are tolerated: carbon-carbon double bonds (entries 8-10), ether functions (entries 5-7), a v iny l bromide (entry 11) and primary halides (entries 12-19). In each case (Table I) , the ^H nmr, i r and mass spectra of the reaction product were in complete agreement with the assigned structure. In a l l cases studied (Table I) , apart from that summarized in entry 13, the reactions were clean and the products were readily isolated. - 37 -Table I : Conversion of a , /3 -acety len ic es ters (90) in to a l k y l ( Z ) - 2 , 3 - b i s ( t r imethy ls tanny l ) -2 -a lkenoates (83) 9 0 Me3Sn SnMe3 C0 2R' Me6Sn2,THF \ = / Pd(PPh3). / \ 3 4 R C0 2R' 83 b c d e f g Entry 90 R R' Condi- Time 83 Y i e l d t i o n s 3 (h) (%) b 1 70 Me Et A 4 124 95 2 114 Et Me A 18 125 88 3 115 i - P r Me A 36 126 90 4 117 c c y c l o p r o p y l Me A 28 127 83 5 118 d tert -BmMe 2 SiO(CH 2 )4 Me A 62 128 82 6 119 c THPOCH 2CH 2CH 2 Me A 15 129 83 7 116 tert-BuMeoSiOCHo Et B e 4 130 83 8 120 c 2 - (2 -cyc lopen teny l )e thy l Me B 6 131 73 9 121 c (3-eyelohexenyl)methyl Me B 3 132 74 10 111 CH 2=CHCH 2CH 2 Me B 4 133 85 11 108 C H 2 - C ( B r ) C H 2 ( C H 2 ) 3 Me B f 2 134 64 12 122S C1CH 2 CH 2 Et B 6 135 89 13 104 BrCH 2 CH 2 Et B 8 136 66 14 100 C1CH 2 CH 2 CH 2 Me B 5 137 86 15 101 BrCH 2 CH 2 CH 2 Me B 6 138 84 16 102 ICH 2 CH 2 CH 2 Me B 6 139 79 17 123 c BrCH 2 (CH 2 )3 Me B 5 140 78 18 95 B r C H 2 ( C H 2 ) 4 Me B 15 141 83 19 99 I C H 2 ( C H 2 ) 4 Me B 6 142 76 React ion c o n d i t i o n s : A: performed at room temperature (20°C) i n THF u t i l i z i n g approx. 0.01 equiv o f Pd(PPh3) 4 and 1 equiv of MegSn 2 . B: performed i n r e f l u x i n g THF u t i l i z i n g reagents as i n A. Y i e l d o f i s o l a t e d , p u r i f i e d product . These mater ia ls were prepared by Dr. J . M . C h o n g . 4 2 T h i s m a t e r i a l was prepared by Dr. B.A. Keay according to the procedure of C h o n g . 4 2 Th is r e a c t i o n was performed at 5 5 - 6 0 ° C . Th is r e a c t i o n was performed u t i l i z i n g a d i f f e r e n t source of p a l l a -dium^)- ' - ' (see t e x t ) . Th is m a t e r i a l was prepared by Mr. J . W a i . ^ 4 - 38 -Tic analysis of the crude product derived from substrate (104) (entry 13), however, showed the presence of one major component and several unidentified components. Similarly, glc analysis of an aliquot indi -cated the presence of one major component and several other components, including hexamethylditin and ethyl 6-bromo-2-pentynoate (104). Since glc and t i c analyses indicated that, as the reaction progressed, more unidentified components were produced, the reaction mixture was sub-jected to workup. After the red-black o i l thus obtained was chromato-graphed three times on s i l i c a gel, a clear, colorless o i l (compound (136)) was isolated in a y i e ld of 66%. The experiment summarized in entry 11, Table I, also deserves additional comment. It was envisaged that under the reaction condi-tions, the product (134) aris ing from the Pd(O)-catalyzed addition of hexamethylditin to the requisite ester, methyl 8-bromonon-8-en-2-ynoate (108) could undergo further reaction (equation 20). In part icular , (20) based on S t i l l e ' s work , 2 ® we envisaged the poss ib i l i ty of an intramolec-ular Pd(0) cross-coupling reaction between the v iny l bromide and v iny l -stannane moieties of (134) to afford the cyc l ic diene (143) (equation 20). However, when a solution of (108) in THF was treated with hexamethylditin and (PPt^^Pd, and the mixture was s t i rred for 20 h at room temperature, glc analysis indicated that no reaction had occurred. - 39 -Moreover, upon refluxing the mixture for 50 h, a considerable amount of unidentified material was evident by both t i c and glc analyses. However, after column chromatography of the crude o i l , a minor amount (<10%) of a mixture of the diene (143) and the addition product (134) was isolated. As a consequence of the fai lure of the above reaction to proceed in THF, the effect of changing the solvent was investigated. As such, when a solution of (108) in either CH3CN, DME or PhH was treated with hexa-methylditin and (PPl^^Pd and the mixture was s t irred for up to 50 h at 60°C, several unidentified materials were evident (glc and t i c analyses). Similar results were obtained when the reaction was carried out in the absence of solvent (neat). Therefore, i t was decided to investigate the reaction u t i l i z i n g an alternative source of Pd(0). In part icular , we were attracted to a recent r e p o r t , ^ which described how a mixture of palladium(II) acetate, triphenylphosphine and triethylamine was used to generate a source of Pd(0) in s i tu . Thus, a solution of the ester (108) in THF was treated with hexamethylditin and an in s i tu solution of Pd(0) in THF. After the mixture had been s t irred at reflux for 2 h, t i c and glc analyses of an aliquot indicated the absence of (108) and the presence of a new component. Removal of the solvent, followed by column chromatography of the crude o i l on s i l i c a gel, afforded 64% of a compound which was subsequently identif ied as methyl (2)-2,3-bis(trimethylstannyl)-9-bromo-2,9-nonadienoate (134). The spectra of the lat ter compound were fu l ly in accord with the assigned structure. The diene (143) was not detected in the crude product mixture by - 40 -either glc or t i c analyses. Furthermore, prolonging the reaction time did not lead to the formation of (143), but resulted instead in the formation of unidentified materials and a lower y ie ld of the addition product (134). The difference in react iv i ty observed by using two different sources of Pd(0) remains unclear. Attempts at effecting an intramolecular Pd(0)-catalyzed coupling of the v iny l bromide and vinylstannane moieties in (134) w i l l be discussed in a later section of this thesis (Section VI of the discussion). Although the Pd(0)-catalyzed addition of other hexaalkylditins to a,B-acetylenic esters was not thoroughly investigated, i t was found that the addition of commercially available hexa-n-butylditin was not a fac i le process. For example, when a solution of ethyl 2-butynoate (70) in THF was treated with hexa-n-butylditin and Pd(PPh.3)4 and the mixture was s t i rred at room temperature or at a s l ight ly elevated temperature (approximately 45°C) the reaction fa i led to go to completion (equation 21). In both reactions, glc or t i c analyses of the crude mixture M e — = = i — C 0 2 E t 70 indicated the presence of the ester (70) and hexa-n-butylditin. The best y i e ld of the addition product (144) that was obtained after column chromatography on s i l i c a gel was 31%. M i t c h e l l 4 3 b had also reported that the Pd(0)-catalyzed addition of hexa-n-butylditin to 1-alkynes is not synthetically useful. BujSn SnBut Pd(PPh a) 4,THF \ / f 2 1 ) .rvBUaSn. / \ Me cOjEt 144 - 41 -Of the a,B-acetylenic esters studied, only ethyl 4,4-dimethyl-2-pentynoate 4 2 (145) fa i led to undergo the Pd(0)-catalyzed addition reaction (equation 22). Thus, when a solution of (145), Pd(PPti3)4 and hexamethylditin in THF was refluxed for 4 days, no product was detected by either glc or t i c analyses. Furthermore, glc analysis of an aliquot of the crude mixture showed only the presence of (145) and hexamethyl-d i t i n , thus indicating that no reaction had occurred. The fai lure of this reaction (equation 22) to proceed most l i k e l y indicates that the M e 6 S n 2 , T H F — ==—C02Et P d ( P P h 3 ) 4 ' no reaction (22) 145 transit ion state of the Pd(0)-catalyzed addition of hexamethylditin to an a,y9-acetylenic ester such as (145) is sensitive to steric crowding about the t r ip l e bond. The fai lure of the ester (145) to undergo the Pd(0)-catalyzed addition reaction is in accord with the work of M i t c h e l l , 4 3 0 who reported that 3,3-dimethyl-1-butyne also fa i l ed to react with hexamethylditin under Pd(0)-catalysis conditions. A possible pathway for the Pd(0)-catalyzed addition of hexamethyl-d i t i n to a ,/3-acetylenic esters is represented by the catalyt ic cycle depicted in Scheme 19. The f i r s t step can be envisaged to be the oxidative addition of hexamethylditin to the PdL,2 catalyst to afford a square planar cis-PdLo(SnMe3)o complex [A].-* 6 Coordination of this la t ter species to the t r ip le bond of the a,^-acetylenic ester would afford an intermediate represented by [B]. The t r ip l e bond could then insert into one of the tin-palladium bonds to afford an intermediate - 42 -Scheme 19 depicted by [C]. This latter species could undergo reductive elimina-tion to afford the corresponding addition product (83) and the palladium catalyst PdL£. The palladium catalyst PdL2 would then undergo another catalyt ic cycle. The catalyt ic cycle depicted in Scheme 19 accounts for the observed stereochemical configuration of the addition products (83). A similar pathway has been evoked to account for the stereochemical configuration of products aris ing from the Pd(0)-catalyzed addition of disilanes to 1-alkynes.^7 In the early part of this section of the discussion i t was mentioned that glc chromatograms of a lkyl (Z)-2,3-bis(trimethylstannyl)-2-- 43 -alkenoates showed evidence of decomposition. This observation led to speculations that these compounds might be thermally unstable. Indeed, the thermal ins tab i l i ty of these compounds was ver i f ied in an early experiment in which a pure sample of methyl (Z)-2,3-bis(trimethyl-stannyl)-6-chloro-2-hexenoate (137) (entry 14, Table I) was d i s t i l l e d ( 9 0 - 9 5 ° C / 0 . 0 1 Torr) in a Kugelrohr bulb-to-bulb d i s t i l l a t i o n apparatus. Tic analysis ( s i l i c a gel , development with 95:5 petroleum ether-diethyl ether) indicated the presence of two major components. The more polar component (Rf •= 0.21) corresponded to the (Z) isomer (137), whereas the less polar component (Rf «=• 0.42) was subsequently found to correspond to methyl (E)-2,3-bis(trimethylstannyl)-6-chloro-2-hexenoate (146). Column chromatography of the crude mixture on s i l i c a gel afforded two separate o i l s , corresponding to (137) and (146). Subjection of each of these o i l s to reduced pressure (vacuum pump, 0.05 Torr) for approximately 1 h afforded 60% of the (Z) isomer (137) and 30% of the (E) isomer (146). The large proportion of the (E) isomer (146) that was formed during the d i s t i l l a t i o n indicated that the thermal isomerization of the (Z) isomer is a fac i le process. Consequently, a l l of the a lkyl (Z) -2 ,3-b is ( tr i -methylstannyl)-2-alkenoates that were prepared, as summarized in Table L, were not d i s t i l l e d but were subjected to reduced pressure (vacuum pump, 0.05-0.1 Torr) to remove any traces of solvent for a period of 1-2 h. The spectral data derived from the (E) isomer (146) was readily interpreted and, as a consequence, the structural assignment was straightforward. For example, the i r spectrum exhibited an absorption at 1685 cm"1 attributable to the carbonyl stretching frequency of an a,8-unsaturated ester function and an absorption at 775 cm"1 due to the - 44 -tin-methyl rocking frequency of a trimethylstannyl group. The . H nmr spectrum of (146) consisted of two sharp 9-proton singlets at 6 0.17 ( 2 J S n . H - 54 Hz) and 6 0.26 (2J.Sn-H ~ 5 5 H z )> a 2-proton multiplet at 6 1.73-1.82, a 2-proton multiplet at 6 2.60-2.66 ( 3 l sn-H ~ 6 0 H z >• a 2-proton t r i p l e t at S 3.55 (J » 7 Hz) and a 3-proton singlet at 6 3.71. Furthermore, high resolution mass spectrometry ver i f i ed that the molecular formula was C^3H2702ClSn2. Up to this point in the discussion conclusive evidence for assign-ment of stereochemical configuration of the compounds obtained from the Pd(0)-catalyzed addition of hexamethylditin to a,/3-unsaturated esters has not been presented. Since we had managed to isolate a compound (146), which had presumably arisen from the thermal isomerization of (137), an opportunity had arisen in which the relative stereochemistry of both compounds could be elucidated. The stereochemical configuration of compounds (146) and (137) was unequivocally established by performing nOe difference experiments on each compound. Thus, irradiat ion of the singlet at 6 3.70 (-OMe) in compound (137) caused signal enhancement of only one of the 9-proton singlets (6 0.25, -SnMe.3). On the other hand, irradiat ion of the singlet at 6 3.71 (-OMe) in compound (146) caused signal enhancement of both of the 9-proton singlets at S 0.17 (-SnMe.3) and 6 0.26 (-SnMe.3). The results of the nOe difference experiments are - 45 -consistent only with the stereochemical configurations depicted in structures (137) and (146), i . e . (Z) and (E) respectively. It should be noted that the result of the nOe difference experiment on compound (137) showed that, of the two 9-proton singlets, the one appearing at higher f i e l d corresponds to the a-Me3Sn group. To ensure that the thermal rearrangement of the (Z) isomer was an ef f ic ient process the following experiment was performed. A neat sample of methyl (Z)-2,3-bis(trimethylstannyl)-6-chloro-2-hexenoate (137) was heated, with s t i r r i n g , at approximately 75°C. After a period of 24 h, t i c analysis indicated the appearance of a new material and the absence of the starting material (137). The pale yellow o i l was d i s t i l l e d to afford a colorless o i l , which was spectrally and chromatographically identical with methyl (E)-2,3-bis(trimethylstannyl)-6-chloro-2-hexenoate (146). This latter material was isolated in a y i e ld of 96%. As a consequence of the eff ic ient thermal isomerization of the (Z) isomer (137) into the (E) isomer (146), the generality of the isomerization process was investigated by employing a variety of alkyl (Z)-2,3-bis(trimethylstannyl)-2-alkenoates (83). As such, the compounds l i s t e d in Table II were prepared in yields ranging from 66-98%. The isomerization process was found to tolerate a variety of functional groups. The functional groups that were tolerated included alkyl groups (entries 1-4), s i l y l and tetrahydropyranyl ether functions (entries 5-7), carbon-carbon double bonds (entries 8-10), a v iny l bromide (entry 11) and primary halides (entries 12-14). The compounds l i s t ed in Table II exhibited nmr, i r and mass spectra that are in complete agreement with the assigned structures (78). - 46 -Table II: Conversion of a lkyl (Z)-2,3-bis(trimethylstannyl)-2-alkenoates (83) into a lkyl (E)-2,3-bis(trimethylstannyl)-2-alkenoates (78) Me3Sn SnMe, Me3Sn CO,R' H — H R C0 2R' R SnMe3 83 78 Reaction Entry 83 R R' conditions 3 ( °C/h) 78 Yie ld (%)b 1 124 Me Et 79/30 77 82 2 125 Et Me 85/18 147 82 3 126 i -Pr Me 80/6 148 98 4 127 cyclopropyl Me 85/7 149 83 5 128 tert-BuMeoSiOCCHoV| Me 95/12 150 94 6 129 THPOCH2CH2CH2 Me 80/6 151 93 7 130 tert-BuMeoSiOCHo Et 81/12 152 86 8 131 2-(2-cyclopentenyl)ethyl Me 80/8 153 81 9 132 (3 -cyclohexenyl)methyl Me 88/48 154 88 10 133 CH2=CHCH2CH2 Me 80/14 155 81 11 134 CH 2 -C(Br)CH 2 (CH 2 ) 3 Me 83/36 156 66 12 137 C1CH2CH2CH2 Me 75/24 146 96 13 95 BrCH 2 (CH 2 ) 3 Me 85/40 157 80 14 99 BrCH 2(CH 2)4 Me 86/21 158 88 A l l reactions were performed neat at a temperature of 75 -95°C. Y ie ld of isolated, d i s t i l l e d product. - 47 -In general, i t was found that the isomerization reaction was a fac i le process that occurred readily at moderate temperatures (75-95°C) over periods of 6-48 hours (Table II) in the absence of solvent. However, the isomerization of compound (134) (entry 11, Table II) was not a clean reaction. Tic analysis of the crude o i l indicated the presence of the desired compound (136), but also present were numerous unidentified components. Furthermore, the yellow reaction mixture contained some insoluble so l id material which was not identi f ied. After the crude o i l had been s t irred at 83CC for 36 h the product (156) was isolated in a y i e ld of 66%. At shorter reaction times t i c analysis indicated only par t ia l isomerization. Although the effect of solvent on the isomerization process was not investigated the problem associated with the isomerization of compound (156) could perhaps be overcome i f the reaction was performed in a solvent such as toluene. Interestingly, the thermal ins tab i l i ty of some of the (Z) isomers (83) l i s t ed in Table II (entries 1-4, 7) is such, that storage of a neat sample of these compounds at 5°C for a period of up to several months results in par t ia l isomerization. However, over such a long period of time, some decomposition of the compounds (83) also occurs. This is part icu lar ly evident from the physical appearance of the crude o i l s , which, upon storage for extended periods of time, become pale yellow and contain insoluble so l id material. Nevertheless, the isomerization process is a fac i le one i f the reaction is performed at a moderately high temperature ( 7 5 - 9 5 ° C ) . A possible mechanistic pathway for the thermal isomerization of compounds (83) to compounds (78) is depicted by equation 23. Upon - 4 8 -Me3Sn SnMe3 Me3Sn OSnMe3 Me3Sn C0 2R' H SnMe3 (23) R 83 C0 2R' R OR' R 159 78 # Me3Sn SnMe3 / O R OR" 160 examination of molecular models corresponding to compounds (83), i t i s apparent, that there ex i s t s a severe s t e r i c i n t e r a c t i o n between the two c i s t r i m e t h y l s t a n n y l groups. On the other hand, i n molecular models corresponding to compounds (78) , t h i s s t e r i c i n t e r a c t i o n has been r e l i e v e d s ince the two t r imethy l s tanny l groups are now t r a n s - r e l a t e d . Hence i t cou ld be expected, that under the r e a c t i o n cond i t i ons , (78) rearranges to the a l l enoate species (159). Presumably, t h i s l a t t e r intermediate could a r i s e v i a a t r a n s i t i o n s tate depicted by (160). Coord inat ion of the oxygen atom with the t i n atom could r e s u l t i n a four -centered t r a n s i t i o n s ta te , which would l ead to the a l l enoate species (159). Th i s l a t t e r species could then undergo i somer iza t ion v i a a four-centered t r a n s i t i o n s tate to a f f o r d the thermodynamically more s tab le product (78). A l t e r n a t i v e l y , the i somer iza t ion process cou ld proceed v i a the pathway depic ted i n Scheme 20. In the d i s c u s s i o n d e a l i n g wi th the previous pathway i t was mentioned that , based on s t e r i c f a c t o r s , the (E) isomers (78) would be expected to be thermodynamically more s table than - 49 -Me3Sn SnMe3 Me3Sn + Me3Sn* C02R' 83 161 Me3Sn C02R' + Me3Sn* R SnMe3 R 78 162 Scheme 20 the (Z) isomers (83). As such, i t could be expected that, i n i t i a l l y , under the reaction conditions, the (Z) isomers (83) could undergo homolytic cleavage of the carbon-tin bond alpha to the ester function to afford the v iny l radical (161) and a trimethylstannyl radica l . The inversion of configuration at a v iny l radical centre has been shown to be a fac i le process.^ 8 Hence, we can consider that the v iny l radical (161) is in equilibrium with the v iny l radical (162). Based on evidence in the l i t e r a t u r e , ^ which suggests that a favourable electronic interaction exists between the t i n atom and the ester function when they are c is related, we can expect the equilibrium to favour the v iny l radical (162). This lat ter species could react with compound (83) or i t could react with a trimethylstannyl radical to afford, in each case, the thermodynamically more stable product (78). In connection with the discussion of the isomerization of compounds (83) to compounds (78), i t is pertinent to note that M i t c h e l l 4 3 ^ reported the photochemical isomerization of the ester (163) to the ester - 50 -(164) (equation 24). Me3Sn SnMe3 Me3Sn C02Me H - — H H C02Me H SnMe3 163 164 (24) Returning to the Pd(0)-catalyzed addition of hexamethylditin to a,B-acetylenic esters, when the reaction was carried out on the diynoate (112) the structural ly interesting diene (165) was isolated in 56% y ie ld (equation 25). For example, when a solution of the ester (112) in THF ,C0 2Et _ ^ Me6Sn2,THF ( y ^ S n M e j (25) Et0 2C Pd(PPh3)4 112 was treated with (PPl^^Pd and hexamethylditin and the mixture was refluxed for 9 h, glc analysis of an aliquot indicated the presence of one major component, which was subsequently identif ied as the diene (165). The structural assignment of the latter compound was clearly established by analysis of the spectral data. For instance, the i r spectrum showed, an absorption at 1698 cm"1 attributable to the carbonyl stretching frequency of an a,y9-unsaturated ester, an absorption at 1611 cm"1 attributable to the carbon-carbon double bond stretching frequency of an a,^-unsaturated ester and an absorption at 771 cm"1 attributable to the tin-methyl rocking frequency. The 1 H nmr of (165) consisted of one 6-proton singlet at 6 0.51 (2J_sn-H = 0^ Hz), a 6-proton t r ip l e t at 6 1.28 (J = 7 Hz), a 2-proton quintet at 6 2.02 (J = 8 Hz), a 4-proton - 51 -t r i p l e t at 6 2.87 (J - 8 Hz) and a 4-proton quartet at 6 4.17 (J - 7 Hz). In addition to the above spectral data, high resolution mass spectrometry showed that the molecular formula for (165) was Ci5H2204S n-It is pertinent to note that the formation of compound (165) cannot be wholly accounted for by the catalyt ic pathway depicted in Scheme 19. An alternative pathway which could account for the formation of (165) remains unclear. It is thus apparent from the preceeding discussion in this section that the palladium(O)-catalyzed addition of hexamethylditin to a,B-acetylenic esters proceeds smoothly and ef f ic ient ly to afford alkyl (Z)-2,3-bis(trimethylstannyl)-2-alkenoates (83). Furthermore, these lat ter compounds are thermally unstable and, upon warming to 75 -95°C, rearrange cleanly to the corresponding (E) isomers (78). B. Spectral data of alkvl (Z)- and (E)-2.3-bis(trimethylstannyl)-2- alkenoates During the course of the preceeding discussion, i t was mentioned several times that the spectral data of a pair of geometrically isomeric a lkyl 2,3-bis(trimethylstannyl)-2-alkenoates show some dist inct d i f fer-ences , and as such the spectral data can provide evidence for the assigned stereochemical configuration. Such differences are clearly seen in the selected ^H nmr chemical shift data of a series of (E) and (Z) isomers, (78) and (83) respectively (Table III) and in the -^H nmr spectra depicted in Figures 1 and 2 (entry 9, Table III) . A character-- 52 -i s t i c trend that can be noticed in Table III is that the chemical shifts of the two 9-proton singlets (Me3Sn groups) of the (Z) isomers (83) are very close together (within 0.03 ppm). On the other hand, the chemical shifts of the two 9-proton singlets (Me3Sn groups) of the (E) isomers (78) are further apart (up to 0.1 ppm). Moreover, the chemical shifts of the 7 protons of the latter compounds are further downfield than those of the corresponding (2) isomers (83). A l l of the examples given in Table III follow this trend except for the pair of isomers given in entry 3. Thus, in the nmr spectra of methyl (Z) - and (E)-2,3-bis-(trimethylstannyl)-4-methyl-2-pentenoate, (126) and (148) respectively, the 7-proton of the (E) isomer resonates at lower f i e l d than the 7 proton of the (Z) isomer (entry 3). Regardless of the anomalous behaviour of these latter compounds, the fact that in a l l other cases (Table III) the 7 protons of the (Z) isomer resonate at higher f i e l d than those of the (E) isomer is unexpected, part icular ly when one considers the anisotropic effect of the carbonyl group of the ester function. On the basis of this effect one would expect the 7-protons of the (Z) isomers ( i . e . those compounds in which the ester function is cis to the 7-protons) to resonate at lower f i e l d . Since this is not the case, presumably the ester function is oriented in a conformation in which the shielding and/or deshielding effects of the carbonyl group are minimal. This presumption is based on the fact that in the series of tr isubst i tuted vinylstannanes of general structure (80A) (vide infra) . In which E — an a lkyl group, the chemical shift of the v inyl methyl group is approximately 2.1 ppm. This value is in close agreement with the chemical shift value of the corresponding v iny l methyl group (6 - 53 Table III: Selected --H nmr chemical shift data for compounds (83) and (78) B A B Me3Sn SnMe3 Me3Sn C02R' H H R C02R' R SnMe3 83 78 A Chemical S h i f t 3 Configu- Com- (SnAMe3) (SnBMe3) 5(7-pro-Entry R R' ration pound 6 6 ton) b 1 Me Et Z 124 0. ,22 0. .25 2, .07 E 77 0. .25 0, .14 2 .22 2 Et Me Z 125 0. .21 0. .22 2, .35 E 147 0. .26 0, .18 2 .49 3 i -Pr Me Z 126 0. .25 0, .28 2 .77 E 148 0, .23 0, .20 2 .66 4 cyclopropyl Me Z 127 0. .23 0. .23 1. .73 E 149 0, .26 0, .17 1. .78 5 tert-BuMeoSiOCHo(CHo)3 Me Z 128 0. .24 0. .25 2, .35 E 150 0. ,25 0. .15 2, .44-2 .51 6 tert-BuMe 2SiOCH 2 Et Z 130 0. .20 0. .23 4. .35 E 152 0. ,24 0. ,15 4. .34 7 (3 -cyclohexeny1)me thy1 Me Z 132 0, .18 0. .20 2. .21-2, .38 E 154 0. ,20 0. ,10 2. ,36-2. .53 8 CH2=CHCH2CH2 Me Z 133 0, .24 0. .245 2. .38-2, .45 E 155 0. .26 0. ,16 2. ,53-2, .61 9 C1CH2CH2CH2 Me Z 137 0. .25 0. .26 2. .47 E 146 0. ,26 0. ,17 2. ,60-2. .66 10 BrCH 2 (CH 2 ) 3 Me Z 140 0. .25 0. .25 2. .36 E 157 0. .26 0. ,17 2. ,47-2. .54 11 BrCH 2 (CH 2 ) 4 Me Z 141 0. .24 0. .25 2. .34 E 158 0. .25 0. ,15 2. .48 Chemical shift (6) was measured relative to the chloroform signal fin (6 7.25) D U in ppm. The spectra were recorded in deuteriochloroform solutions. S (7-protons) refers to the chemical shift of the protons 7 to the ester function. - 54 -Me3Sn C02Me SnMe, X F i g . 2: The 400 MHz X H nmr spectrum of (146) Me,Sn SnMe3 CO.Me Cl 137 A _ A I 3 2 F i g . 1: The 400 MHz X H nmr spectrum of (137) - 55 -Me3Sn H C02Et Me3Sn SnMe3 H Me E 80A Me 77 C0 2Et 2.07) i n compound (77). In f a c t , i t seems apparent that the 7-proton of resonate at lower f i e l d than those of the (Z) isomers due, perhaps, to the deshielding e f f e c t of the t i n atom. Nevertheless, t h i s trend, which i s summarized i n Table I I I , enables one to d i s t i n g u i s h between a p a i r of geometric isomers (78) and (83). The chemical s h i f t s of the two 9-proton s i n g l e t s (5 (Sn AMe3)) and (S (Sn^Me3)) of the (Z) isomers (83) were assigned to the respective trimethylstannyl groups on the basis of the following evidence. In an nOe d i f f e r e n c e experiment performed on compound (137) (entry 9, Table I I I ) , as was described e a r l i e r , i r r a d i a t i o n of the s i n g l e t at 6 3.70 (-OMe) caused enhancement of the 9-proton s i g n a l that corresponded to the high f i e l d s i g n a l . Therefore, t h i s resonance was assigned to the SnMe3 group on the a carbon of the unsaturated ester (137) (5(Sn AMe 3)). By analogy, the chemical s h i f t s of the two 9-proton s i n g l e t s i n the (Z) isomers (Table III) were designated accordingly. That i s , i n each case, the resonance at higher f i e l d was assigned to the trimethylstannyl group a to the ester function. On the other hand, the corresponding chemical s h i f t assignments of the two 9-proton s i n g l e t s of the (E) isomers (78) were assigned to the respective trimethylstannyl groups on the basis of the following evidence. In the next chapter of the discussion (III.A) the formation the (E) isomers ( i n which the Me3Sn group and the 7-protons are c i s ) - 56 -Me 3 Sn C0 2 R' H R E 80 of tr isubstituted vinylstannanes of general structure (80) w i l l be discussed. The trimethylstannyl group and the ester function in these compounds are cis—related, as is the case in the (E) isomers (78). The chemical shift of the 9-proton singlet (SnMe3 group) of each of the compounds (80) was found to correspond closely to that of the high f i e l d Me3Sn singlet of the two 9-proton singlets of the (E) isomers (78). Consequently, by analogy, the resonance at higher f i e l d was assigned to the trimethylstannyl group on the 6 carbon of the unsaturated esters (78) (5(SnBMe 3)). A tool that further corroborated the stereochemical assignments of the two geometric isomers, (83) and (78), was 1 3 C nmr spectroscopy (Tables IV and V) . If one considers the selected chemical shift data presented in Table IV, the most s tr iking feature to note is the large difference in the chemical shifts observed for the carbonyl carbons of a given pair of geometrically isomeric a lkyl 2,3-bis(trimethylstannyl)-2-alkenoates. For instance, for the methyl 2,3-bis(trimethylstannyl)-2-butenoates (entry 1) the chemical shifts of the carbonyl carbons (5C^, Table IV) are 6 159.8 ((Z) isomer) and S 180.8 ((E) isomer), a difference of 21 ppm. Most of the Isomeric pairs l i s t ed in Table IV show a similar difference in chemical shi f t . The smallest difference (10.6 ppm) is observed for the isomeric pair given in entry 5 (R = tert-BuMe2Si0CHo-). The chemical shifts of the carbonyl carbon of the - 57 -Table IV: Se lec ted 1 3 C nmr chemical s h i f t data f o r compounds (78) and (83) A Me3Sn C0 2R' Me3Sn SnMe3 R D S nMe 3 R D C 0 2 R ' A 78 83 C h e m i c a l s h i f t 8 E n t r y R R' C o n f i g u - Com- « ( C A ) « ( C B ) < ( C C ) « ( C D ) b « ( S n M e 3 ) r a t i o n p o u n d 1 He E t Z 124 159. 8 149. .9 171 .7 26 .3 -7 2 , -6 .8 E 77 180. .8 144. ,2 171, .6 28, .2 - 5 • 9 , -6 .7 2 E t He Z 125 166. 8 148. .2 172, .3 34, .0 -6 • 8 , -6 .7 E 147 185 .6 143. .4 172 .2 34, .5 -6 • 1 , -6 .6 3 i - P r He Z 126 170. .9 146, 6 172, .8 40 , .3 -6 . 3 , - 4 , .5 E 148 184. .2 143, .7 172, .7 4 3 , .1 -4 • 4 , -6 .2 4 t e r t - B u M e 2 S i O C H ; ( C H 2 > 3 He Z 128 165. .3 148, .8 172 .3 40 , .9 -6 . 8 , -6 .7 E 150 184. .4 143, 8 172, .2 4 1 . .6 - 6 . 1 . - 6 , .6 5 j p _ x - BuMe 2 S i OCH2 E t Z 130 166. .1 147, .1 171 .6 68 , .0 -6 . 5 , - 5 .8 E 152 177, .7 144. .9 171 .9 69. .9 -6 0, - 6 , .1 6 ( 3 - c y c l o h e x e n y l ) m e t h y l He Z 132 163. .7 149. .9 172 .4 4 7 . ,7 - 6 . 6 , - 6 . ,5 E 154 184. .2 144, .7 171 .7 4 7 . .7 - 5 . 5 , - 6 , .2 7 C H 2 - C H C H 2 C H 2 He Z 133 163 .2 149, .6 172 .1 40 . .3 - 6 8 , - 6 . ,7 E 155 182. .3 144, .6 172, .1 4 0 . 8 - 6 . • 0 , - 6 . .5 8 C H 2 - C ( B r ) C H 2 ( C H 2 ) 3 He Z 134 164. .8 149. .2 172, .2 40 . 6 - 6 . • 7 , - 6 . .7 E 156 183, .8 144, .2 172, .1 4 1 . 3 - 6 , 0, - 6 . .5 9 C1CH 2 CH 2 CH 2 He Z 137 163, .2 150. 8 172, .1 4 4 . .4 - 6 7 , - 6 . .7 E 146 182. .3 145. .5 172 .0 4 4 . .3 - 6 , 0, - 6 . ,4 10 B r C H 2 ( C H 2 > 3 He z 140 164, .4 147. .7 172 .1 39. 8 -6 8 , - 6 . .7 E 157 183. .5 144. .6 172 .0 4 0 . ,7 - 6 . 0, - 6 . .5 11 B r C H 2 ( C H 2 ) 4 He Z 141 164. .8 149 . .2 172 .1 4 0 . .6 - 6 . 8 , - 6 . ,7 E 158 183. .9 144. ,1 172 .1 4 0 . 4 - 6 . 0. - 6 . 5 Chemical s h i f t (6) was measured r e l a t i v e to the deuter iochloroform s i g n a l (5 7 7 . 0 ) 6 0 i n ppm. A l l spect ra were recorded on deuter io -chloroform s o l u t i o n s . o"(CD) r e f e r s to the chemical s h i f t o f the a l l y l i c carbon 7 to the es te r f u n c t i o n . - 58 -(Z) isomers appeared in the range 159-171 ppm, while for the (E) isomers the range was 177-186 ppm. As such, the stereochemical configuration of a pair of geometric isomers could be ver i f ied by comparing the chemical shifts of the carbonyl carbons. Upon comparison with the nmr chemical shifts of the v iny l i c carbons of methyl (E)-2-butenoate,^ the high f i e l d signals of the v i n y l i c carbons of the geometric isomers (83) and (78) were assigned to the carbon (5(Cg)) alpha to the ester function. It can be noted that the chemical shift of the latter carbon (5(Cg)) decreased by approximately 5 ppm in going from the (Z) isomer (83) to the (E) isomer (78). On the other hand, the chemical shift of the carbon (5(CQ ) ) beta to the ester remained re lat ive ly unchanged. The signals due to the two 3-carbon singlets corresponding to the two trimethylstannyl groups of both the (E) and (Z) isomers appear at high f i e l d relative to tetramethylsilane (TMS). Thus, in a l l cases (Table IV) the chemical shifts are at approximately -6.0 ppm. These signals were not assigned to specific trimethylstannyl groups of the compounds (78) and (83). Table V contains a summary of tin-carbon coupling constants observed in the nmr spectra of compounds (78) and (83). These constants range from one bond coupling (^isn-c) t o t ^ i r e e hond coupling (3J.Sn-c) • The ^J.sn-C v a l u e s a r e a n average of the H^Sn and ^-^Sn signals, whereas the 2J.Sn-C a n d ^Sn-C v a l u e s refer to the H 9 S n signal,^1 since in these lat ter cases the centres of the H^Sn a n d H 7 g n sate l l i tes are unresolved. The largest tin-carbon coupling constants occur for coupling through one bond. Thus, these values range from 326 to 346 Hz - 59 -Table V: Se lec ted 1 3 C nmr J va lues f o r compounds (78) and (83) Me3Sn C02R' Me3Sn SnMe3 \ £ J / W / \ A i \ R D SnMe3 R D C02R' A 78 83 •ISn-C ( » - ) Intry R R* Configu-ration Com-pound < liSn •Me)* ( 2 i S n - C n ) b ( 3 i S n - C n ) C ( 3 iSn C 1 Me Et Z 124 326, 342 62 71 E 77 344, 339 62 62 2 Et Me Z 125 338, 332 57 68 6 5 E 147 342, 340 57 57 7 7 3 i - P r Me Z 126 340, 337 52 65 13 0 E 148 340, 337 51 59 13 0 ££i£-BuMe 2 Si0CH 2 (CH 2 )3 Me Z 128 338, 331 55 66 8 0 E 150 343, 332 55 55 8 3 5 tert-BuMe2S10CH3 Et Z 130 345, 337 35 76 -E 152 345, 332 41 61 -6 (3-cyclohexenyl)methyl Me Z 132 340, 331 53 65 6 6 E 154 342, 340 53 53 6 9 7 CH2-CHCH2CH2 Me Z 133 339, 332 55 66 7 0 E 155 344, 340 55 55 7 9 S CH 2 -C(Br)CH 2 (CH 2 ) 3 Me Z 134 338, 330 55 66 7 6 E 156 341, 340 55 55 7 3 9 C1CH2CH2CH2 Me Z 137 337, 333 55 66 7 0 E 146 346, 341 55 55 7 9 10 BrCH 2 (CH 2 ) 3 Me Z 140 342, 327 55 66 7 8 E 157 341. 340 54 54 7 0 11 BrCH2(CH2>4 Me Z 141 342, 326 54 66 8 1 E 158 343, 342 55 55 7 6 '^Sn-Me- coupling between the t in atom and the neighbouring carbon of a methyl group. "'isn-C : coupling between the t in atom of a fi-SvHe^ group and the D a l l y l i e carbon 7 to the ester function. 3 iSn-C : coupling between the t in atom of an Q-SnMe3 group and the D a l l y l i c carbon 7 to the ester function. 3 iSn-C : coupling between the t in atom of a 0-SnMe3 group and the D ' carbon adjacent to the a l l y l i c carbon (C D ) . Me,Sn MejSn C02R* Me3Sn ^ Me,Sn SnMe3 Co SnMe3 °D Cp C02R' 3 i S n - C n ' 3 i S n - C n (ii*) 2 2sn-C n 3 i S n - C D ( i I £ H £ ) - 60 -(Table V ) . There seems to be l i t t l e c o r r e l a t i o n between the magnitude o f the *";Isn-C a n d t b e s tereochemical c o n f i g u r a t i o n of the isomers (78) and (83). The ""^Sn-C values that appear i n Table V are of s i m i l a r magnitude to those reported by M i t c h e l l 4 3 b f o r ( Z ) - 1 , 2 - b i s ( t r i m e t h y l -s t a n n y l ) - 1 - a l k e n e s . A l s o o f i n t e r e s t i n Table V are the ^J_Sri-Cn v a l u e s . A feature c o n s i s t e n t throughout a l l examples presented i n Table V i s that J s n - C ^ ( t rans) > ^J_sn-Cjj ( c i s ) . 6 2 For example, i n the p a i r of isomers g iven i n entry 1, the " \ l s n - C n va lues are 71 and 62 Hz, f o r the (Z) and (E) isomers, r e s p e c t i v e l y . Th is d i f f e r e n c e i n magnitude (-10 Hz) between ^-Sn-Cp ^ n t b e (2) a n d ( £ ) isomers i s apparent f o r a l l cases presented i n Table V and, thus enables one to d i s t i n g u i s h the c o n f i g u r a t i o n of a g iven p a i r . I n t e r e s t i n g l y , the ^ i s n - C ^ ( c is ) values ( i . e . those c o r r e -sponding to the (E) isomer) are equal to the 2 J _ s n - C n va lues f o r a l l examples l i s t e d i n Table V apart from the (E) isomers g iven i n e n t r i e s 3 and 5. For the (E) isomer (152) given i n entry 5 (R = ter t -BuMe 2 Si0CH 2 ) the va lue of ^J.Sn-C n l s 6 1 whereas the 2J_Sn-Cjj va lue i s 41 Hz. Obviously i n t h i s l a t t e r case the a l l y l i c oxygen atom exerts some e l e c -t r o n i c e f f e c t that a f f e c t s the magnitude of the coup l ing constants . However, the reason f o r the anomaly that appears i n the case of the (E) isomer (148) g iven i n entry 3 (R = i.-Pr) i s not c l e a r . A l s o of note i n Table V are the i s n - C ' v a l u e s , which are s m a l l , genera l l y l e s s than 9 Hz. A fu r ther feature to note i n Table V are the 2 J . S n - C n v a l u e s . Not unexpectedly, these va lues are the same f o r any given p a i r of geometric isomers regard less of the stereochemical c o n f i g u r a t i o n . Th is i s - 61 -Me3Sn SnMe3 CO. Me I | I I I I ] M I 1 | ! 1 200 ISO a i ] l i T i | i r n ]•—i I'TTT i T i ] i T i i i i 11 i | i i i i | i i i i | n i i | i T i i | i i i i tT r r f | i i i i | IT-T T ] TT'1 I | 11 i i | i i i i | i i 160 140 120 100 60 60 40 20 0 PPM I f * " Fig. 3: The 75.6 MHz 1 JC nmr and APT spectra of (141) 62 -Me3Sn C02Me SnMe, i A I 200 r r p IbO T 140 a — b a rp-r-100 i i i i | i r i • 60 T" 60 *0 20 0 P ? u I I I F i g . 4: The 75.6 MHz 1 J C nmr and APT spectra of (158) - 63 -apparent i n a l l cases presented i n Table V apart from the p a i r of isomers given i n entry 5 (R — tert-BuMeoSiOCrfo). The 1 3 C nmr spect ra depic ted i n Figures 3 and 4 serve to i l l u s t r a t e the features d iscussed i n t h i s s e c t i o n of the t h e s i s . I t i s pe r t inen t to note that the m u l t i p l i c i t y of the 1 3 C nmr data which appears i n the experimental s e c t i o n was determined by the APT technique. A f i n a l s p e c t r a l t o o l which was used i n a few examples to corrobor -ate the stereochemical c o n f i g u r a t i o n assigned to the isomers (78) and (83) was 1 1 9 S n nmr s p e c t r o s c o p y 6 1 (Table V I ) . Although only three p a i r s of geometric isomers were s tud ied the r e s u l t s obtained i n d i c a t e that 1 1 9 S n nmr spectroscopy can be used e f f e c t i v e l y i n ass ign ing the s te reo-chemical c o n f i g u r a t i o n of a given p a i r of isomers. A s t r i k i n g feature of the data summarized i n Table VI i s the d i f f e r e n c e i n the ^ i s n - S n va lues i n going from a (Z) to an (E) c o n f i g u r a t i o n . For example, fo r the p a i r of isomers g iven i n entry 1 the ^J_Sn-Sn v a l u e *- s 3 3 4 H z f ° r t b e (Z) isomer (128) and 562 Hz fo r the (E) isomer (150). Such a large increase of over 200 Hz i s a lso apparent fo r the p a i r of isomers given by e n t r i e s 2 and 3. Furthermore, the chemical s h i f t s of the two t i n s i g n a l s i n the (E) isomers are approximately 6* -50 ppm, whi le i n the (Z) isomers they are approximately 6 -36 ppm. The former chemical s h i f t va lues are c o n s i s t e n t f o r a l l of the (E) isomers l i s t e d i n Table VI except f o r the (E) isomer given by entry 5 (E - 1 - P r ) . The 1 1 9 S n nmr spect ra dep ic ted i n F igures 5 and 6 serve to i l l u s t r a t e the d i s t i n c t d i f f e r e n c e s apparent i n a p a i r of geometric isomers. In c o n c l u s i o n , i t i s apparent from the preceeding d i s c u s s i o n that a combination of ^H, 1 3 C and 1 1 9 S n nmr spectroscopy can provide conc lus ive - 64 -Table VI: 1 1 9 S n nmr data for compounds (78) and (83) Me3Sn H C02R' R SnMe3 78 Me3Sn H SnMe3 R C02R' 83 Entry R R' Configu-ration Com-pound 6"(SnMe 3>a ( 3^Sn-Sn) 1 tert-BuMeoSiOCHo(CHo)3 Me Z 128 -37. .2, -36. .4 334 E 150 -51. 5, -50. ,1 562 2 C1CH2CH2CH2 Me Z 137 -35, .4, -35. .3 317 E 146 -50. 2, -49. ,3 527 3 BrCH 2 (CH 2 ) 4 Me Z 141 -36, • 9, -36. .0 330 E 158 -51. 5, -50. .5 558 4 Et Me E 147 -51. 1, -50. 7 562 5 i -Pr Me E 148 -60. 2, -44. ,5 572 6 tert-BuMeoSiOCHo Et E 152 -48. 8, -47. ,1 510 7 CH2=CHCH2CH2 Me E 155 -51, .6, -51. ,0 551 8 (3 -cyclohexenyl)me thy 1 Me E 154 -51. .8, -50. ,2 564 Chemical shift (5) was measured relative to the Me4Sn signal (6 - 0) in ppm. A l l spectra were recorded on deuteriochloroform solutions. J is measured in Hz and represents coupling between 1 1 9 S n and 1 1 9 S n . - 65 -F i g . 6: The 111.8 MHz 1 1 9 S n nmr spectrum of (158) Fi g . 5: The 111.8 MHz l l s S n nmr spectrum of (141) - 66 -evidence for the stereochemical configuration of a lkyl (E)- and (Z)-2,3-bis(trimethylstannyl)-2-alkenoates. C. Preparation of (E)-N.N-dimethyl-2.3-bis(trimethylstannyl)-2- alkenamides On the basis of the work described above, i t is evident that internal alkynes containing an electron-withdrawing group attached to the t r ip l e bond (e.g. a,B-acetylenic esters) undergo fac i le Pd(0)-catalyzed addition of hexamethylditin. It was of interest to probe the poss ib i l i ty of using other internal alkynes that are activated by an electron withdrawing group. As a preliminary study, the poss ib i l i ty of u t i l i z i n g a,B-acetylenic N,N-diethylamides was examined. Thus, to a solution of N,N-dimethyl-2-butynamide (166) in 20 mL of THF was added 1 equiv of hexamethylditin and 0.01 equiv of (PPl^^Pd and the mixture was s t i rred at room temperature. After the reaction mixture had been s t i rred for 44 h, glc analysis of an aliquot indicated the appearance of a new peak and the absence of the signal corresponding to the amide (166). Tic analysis ( s i l i c a gel, development with 1:1 petroleum ether-ethyl acetate) of the mixture indicated the presence of two major components (Rf — 0.36 and 0.60) and one minor component (Rf = 0.95) corresponding to hexamethylditin. After removal of the solvent, the two major products were separated by column chromatography of the crude mixture on s i l i c a gel to afford two different o i l s . The major compound (80% of the product) was subsequently identif ied as (Z)-N.N-di-- 67 -methyl-2,3-bis(trimethylstannyl)-2-butenamide (167) and the minor compound (20% of the product) was identif ied as (E)-N,N-dimethyl-2,3-bis(trimethylstannyl)-2-butenamide (168) (equation 26). Me ===== CONMe2 Me3Sn SnMe3 Me3Sn CONMe2 — H • H -Me CONMe2 Me SnMe3 166 167 168 The spectral data derived from the two compounds (167) and (168) were readily interpreted. The i r spectra of both compounds showed absorptions at 1620 cm' 1 , attributable to the carbonyl stretching frequency of an a,B-unsaturated amide function, and absorptions at 775 and 770 cm"1 attributable to the tin-methyl rocking frequency of the trimethylstannyl groups. The 1 H nmr spectrum of the (Z) isomer (167) consisted of two sharp 9-proton singlets at 6 0.20 (2J_Sn-H ~ ^ 4 ^z) and 6 0.22 ( 2Isn - H " 5 4 H z ) • a 3-proton singlet at 5 1.94 (3J_sn-H = 4 5 H z ' 4 J S n . H - 11 Hz) and two 3-proton singlets at 6 2.91 and 6 2.95. In contrast, the nmr spectrum of the (E) isomer (168) consisted of two 9-proton singlets at 5 0.12 ( 2J_s n-H = 5 3 H z > a n d 6 ° - 2 5 ( 2 j-Sn-H " 5 3 Hz), a 3-proton singlet at 6 2.05 ("'j.Sn-H ~ 4 6 ^z, 4J.Sn-H ~ 1 1 ^z) and a broad 6-proton singlet at S 2.92. In addition to the above spectral data, high resolution mass spectrometry ver i f ied that the molecular formula for both isomers was C^2H270NSn2. Although direct evidence for the stereochemical configuration of the two compounds (167) and (168) was not obtained, there was enough indirect evidence to show that our assignments were correct. The over-- 68 -whelming piece of evidence, of course, was the f a c t that i n the Pd(0)-ca ta lyzed a d d i t i o n of hexamethyldi t in to the amide (166) two isomeric products were obtained. Based on the e a r l i e r f i n d i n g that a l k y l ( Z ) - 2 , 3 - b i s ( t r i m e t h y l s t a n n y l ) - 2 - a l k e n o a t e s are thermal ly unstable , one would p r e d i c t that of the two products (167) and (168), the (E) isomer (168) had a r i s e n as a r e s u l t of in_ s i t u i somer iza t ion o f the (Z) isomer (167). Indeed, when a s o l u t i o n of the (Z) isomer (167) i n THF was r e f l u x e d for 1.5 h , t i c ana lys i s i n d i c a t e d that (167) had completely i somerized to the corresponding (E) isomer (168) (equation 27). Me3Sn SnMe3 H THF.A 1.5h Me CONMe2 1 67 Furthermore, the ^H nmr spectra of the two isomers (167) and (168) showed pat terns very s i m i l a r to the ^H nmr spectra of methyl (E) - and (Z) -2 ,3 -b i s ( t r imethy l s tanny l ) -2 -butenoate s (77) and (124), r e s p e c t i v e l y . For example, i n the ^H nmr spectra of the (Z) isomers (167) and (124), the two 9-proton s i n g l e t s due to the t r i m e t h y l s t a n n y l groups appear very c lose together (AS = 0.02 and 0.03 ppm, r e s p e c t i v e l y ) . On the other hand, i n the ^H nmr spectra of the two (E) isomers (168) and (77) , the two corresponding 9-proton s i n g l e t s appear fur ther apart (AS = 0.13 and 0.09, r e s p e c t i v e l y ) . Moreover, the resonances of the v i n y l methyl groups i n the two (Z) isomers are at h igher f i e l d than the two c o r r e -sponding s igna l s of the two (E) isomers, r e s p e c t i v e l y . Although the Pd(0) -cata lyzed a d d i t i o n of hexamethyldi t in to a,8-a c e t y l e n i c N , N - d i e t h y l a m i d e s (169) was not i n v e s t i g a t e d extens ive ly i t Me3Sn CONMe2 (27) Me SnMe3 168 i 1 H - 69 -was found to be a r e l a t i v e l y f a c i l e process for a number of amides (Table V I I ) . I t should be noted that i n each case, except for the experiment summarized i n entry 1, only the (E) isomer (170) was i s o l a t e d under the s p e c i f i e d r e a c t i o n c o n d i t i o n s . The f u n c t i o n a l groups present i n the s t a r t i n g mater ia l s that were t o l e r a t e d dur ing the a d d i t i o n were a l k y l groups ( entr ies 1,2) , a primary bromide (entry 3) and a s i l y l ether f u n c t i o n (entry 4) (Table V I I ) . Although, i n the l a s t two examples ( entr i e s 3 and 4) , the react ions were performed i n r e f l u x i n g THF, r e a c t i o n times were cons iderably longer when compared to c o r r e -sponding examples i n v o l v i n g a , ^ - a c e t y l e n i c es ters (Table 1) . In a l l cases (Table VII) the ^H nmr, i r and mass spectra of the products were found to be i n complete agreement with the assigned s t r u c t u r e s . The pathway for the Pd(0) -cata lyzed a d d i t i o n of hexamethyldi t in to a,^-acetylenic N,N-dimethylamides (169) to a f f o r d the corresponding (Z) -N ,N-d imethy l -2 ,3 -b i s ( t r imethy l s tanny l ) -2 -a lkenamides i s most l i k e l y analogous to that depic ted i n Scheme 19. The subsequent i somer iza t ion of these l a t t e r compounds in to the corresponding (E) isomers probably fol lows a mechanist ic pathway analogous to that depic ted i n equation 23 (or Scheme 20). I t i s evident from the preceeding d i s c u s s i o n that the (Z) isomers obtained from the corresponding a,B-acetylenic N,N-dimethy1-amides (166) are l e s s s table than the (Z) isomers obtained from the corresponding a,B-acetylenic esters (90). This d i f f erence i n s t a b i l i t y can be a t t r i b u t e d to the greater s t e r i c i n t e r a c t i o n imposed by the amide group as depic ted i n s t ruc tures (177) and (177A) vs that of the es ter group as depic ted i n s t ruc ture (178). As a consequence, i t would be expected that the energy requ ired for the i somer iza t ion process to occur - 70 -Table VII: Conversion of a,/9-acetylenic N,N-dImethylamIdes (169) into (E)-N,N-dimethyl-2,3-bis(trimethylstannyl)-2-alkenamides (170) Me3Sn CONMe2 •CONMe, H 169 R i 7 0 S n M e 3 Entry 169 Reaction conditions 3 ( °C/h) 170 Yie ld (%)b 166c Me 20/44 168 13c 171c Et 20/72 174 48 172* BrCH2CH2CH2 67/26 175 75 173c ;t^rt-BuMe 2SiOCH 2CH 2CH 2 67/48 176 63 Reactions were performed in solutions of THF u t i l i z i n g approximately 0.01 equiv of (PPt^^Pd and approximately 1 equiv of MegSn2. Y ie ld of isolated, d i s t i l l e d product. These materials were prepared by Dr. J .M. Chong. 4 2 50% of the corresponding (Z) Isomer was also isolated. We thank Dr. J .M. Chong for a sample of this material. - 71 -i n (Z)-N,N-dimethyl-2,3-bis(trimethylstannyl)-2-alkenamides such as (167) would be le s s than that required f o r the corresponding a l k y l (Z)-2,3-bis(trimethylstannyl)-2-alkenoates (83). The d i f f e r e n c e i n the rate of isomerization i s borne out experimentally. For instance, when the Pd(0)-catalyzed a d d i t i o n r e a c t i o n i s performed i n r e f l u x i n g THF, a, 8 -acetylenic esters lead to the corresponding (Z) isomers, whereas a,8-acetylenic N,N-diethylamides lead to the corresponding (E) isomers. I I I . Chemistry of a l k y l (Z)- and (E)-2,3-bis(trimethylstannyl)-2-alkenoates A. Transmetalation of the t i t l e compounds and r e a c t i o n of the resultant  intermediates with e l e c t r o p h i l e s Having established an e f f i c i e n t and f a c i l e route f o r the preparation of a l k y l 2,3-bis(trimethylstannyl)-2-alkenoates, a program was i n i t i a t e d to determine whether or not these substances could be used e f f e c t i v e l y i n synthesis. Chong 2! had shown that the o-SnMe3 group of ethyl (E)-2,3-bis(trimethylstannyl)-2-butenoate (77) could be removed - 72 -selectively by transmetalation with methyllithium and that the resultant nucleophilic intermediate reacted with a variety of reactive electro-philes to afford trisubstituted vinylstannanes (equation 11). As a consequence, our i n i t i a l objective in probing the u t i l i t y of the t i t l e compounds in synthesis was to determine the generality of the trans-metalation reaction by employing alkyl 2,3-bis(trimethylstannyl)-2-alkenoates that possessed different functional groups and to determine the react iv i ty of the resultant nucleophilic intermediates by treating them with a variety of electrophiles. The conditions under which the transmetalation reaction was per-formed is i l lus trated by the following example. Thus, a solution of methyl (Z)-2,3-bis(trimethylstannyl)-2-pentenoate (125) in THF was treated with a solution of methyllithium in ether at -98°C for 15 min. 3-Iodopropene was added and the solution was s t irred at -98°C for 30 min and at -78°C for 45 min. After appropriate workup, the ester (179) was isolated as the sole substitution product in 85% y ie ld (equation 28). Me3Sn SnMe3 Me3Sn C02Me 1.MeLI,THF,-98°C \ = / (28) 2. CH2CHCH2I / \ / C02Me -98° — -78°C 125 3" H + 179 Determination of the constitution of compound (179) was readily accomplished by analysis of the H^ nmr spectrum, which showed the presence of one 9-proton singlet (Me3Sn group) as well as signals corresponding to an a l l y l group. These lat ter signals consisted of a 2-proton dt at 6 3.21 (J •= 6, 1.5 Hz), a 1-proton ddt at fi 4.97 (J - 17, - 73 -2, 1.5 Hz), a 1-proton ddt at 6 4.98 (J = 10, 2, 1.5 Hz) and a 1-proton ddt at 6 5.87 (J - 17, 10, 6 Hz). Furthermore, high resolution mass spectrometry confirmed that the molecular formula was C^2l^ 2402^^2 * The results of reactions involving the use of other alkyl 2,3-bis-(trimethylstannyl)-2-alkenoates and a variety of alkylating agents are summarized in Table VIII. These reactions proceeded in yields ranging from 40% to 81%, although in some cases the yields have not been optimized. A feature to note in the results summarized in Table VIII is that the yields of substitution products (80) were generally good when reactive alkylating reagents were employed. For example, the alkylating agents 3-iodopropene (entries 15-17), iodomethane (entries 7, 11, 13), 3-iodo-2-methylpropene (entries 3, 8, 10, 14) and l-bromo-3-methyl-2-butene (entries 5, 9, 12), gave good to excellent yields of the products (80). In a l l of these experiments involving the use of reactive halides, unidentified polymeric material was also present in the solu-tions. However, this latter material was readily removed from the crude o i l by column chromatography of the mixture on s i l i c a gel or by direct d i s t i l l a t i o n , thus affording the ester (80) as the sole substitution product. On the other hand, isolated yields of the substitution product (80) were lower when less reactive halides (for example, l -chloro-3-iodopropane (entry 1) and 2,5-diiodo-l-pentene (entry 4)) were employed. In these cases, glc analyses of the solutions indicated the presence of varying amounts (up to 10%) of the corresponding products in which E=H. Also evident upon workup was a higher proportion of unidentified polymeric material. Efforts were made to increase the product yields in those cases involving "unreactive" alkylating agents. However, these - 74 -T a b l e VI I I : Transmetalat ion of a l k y l (Z) or ( E ) - 2 , 3 - b i s ( t r i m e t h y l s tanny l ) -2 -a lkenoates ((83) or (78)) and r e a c t i o n of the r e s u l t a n t intermediates with e l e c t r o p h i l e s Me3Sn SnMe, Me3Sn C02R' M e,Sn C02R" H « H - i r - H R C02R' R SnMe3 R E 83 78 80 E n t r y 3 (83 o r 7 8 ) b R R' E X C 80 Y i e l d (%)d 1 77 Me E t I C H 2 C H 2 C H 2 C 1 180 54 2 77 Me E t C l S l M e 3 181 70 3 77 Me E t I C H 2 - C M e - C H 2 e 182 69 4 77 Me E t I C H 2 C H 2 C H 2 - C I - C H 2 f 183 42 5 77 Me E t B r C H 2 - C H - C M e 2 184 66 6 77 Me E t B r C H 2 - O C - S i M e 3 185 40 7 153 2 - ( 2 - c y c l o p e n t e n y l ) e t h y l Me IMe 186 72 8 153 2 - ( 2 - c y c l o p e n t e n y l ) e t h y l Me I C H 2 - C M e - C H 2 e 187 68 9 153 2 - ( 2 - c y c l o p e n t e n y l ) e t h y l Me B r C H 2 - C H - C M e 9 I C H 2 - C M e - C H 2 ^ 188 71 10 152 t . e r t - B u M e 2 S i 0 C H 2 E t 189 74 11 152 t e r t - B u M e 2 S i O C H 2 E t IMe 190 74 12 152 t e r t - B u M e 2 S i G C H 2 E t B r C H 2 - C H - C M e 2 191 81 13 149 c y c l o p r o p y l Me IMe 192 79 14 149 c y c l o p r o p y l Me I C H 2 - C M e - C H 2 e 193 76 15 125 E t Me I C H 2 - C H - C H 2 179 85 16 126 i - P r Me I C H 2 - C H - C H 2 194 73 17 133 C H 2 - C H C H 2 C H 2 Me I C H 2 - C H - C H 2 195 75 R e a c t i o n c o n d i t i o n s : A s o l u t i o n ( T H F , - 9 8 ° C ) o f (78) o r (83) was t r e a t e d w i t h M e L i ( 1 . 2 e q u i v ) , t h e r e a c t i o n m i x t u r e was s t i r r e d a t - 9 8 ° C ( 10 -35 m i n ) , t h e a p p r o p r i a t e a l k y l a t i n g a g e n t (EX) was a d d e d , t h e r e a c t i o n m i x t u r e was s t i r r e d a t - 9 8 ° C (30 min) a n d a t - 7 8 ° C (45 m i n - 2 . 5 h ) a n d t h e n s a t u r a t e d a q u e o u s NH4CI was a d d e d . I n a l l c a s e s t h e s t a r t i n g m a t e r i a l was t h e ( £ ) i s o m e r ( 7 8 ) , e x c e p t f o r t h e e x a m p l e s g i v e n i n e n t r i e s 1 5 - 1 7 . I n e a c h o f t h e s e c a s e s , t h e s t a r t i n g m a t e r i a l was t h e (Z) i s o m e r ( 8 3 ) . T h e s e m a t e r i a l s were p a s s e d t h r o u g h a c o l u m n o f a c t i v i t y I b a s i c a l u m i n a i m m e d i a t e l y p r i o r t o u s e , w i t h t h e e x c e p t i o n o f l - b r o m o - 3 - m e t h y l - 2 - b u t e n e ( e n t r i e s 5 , 9 , 12) w h i c h was d i s t i l l e d i m m e d i a t e l y p r i o r t o u s e . Y i e l d o f p u r i f i e d d i s t i l l e d p r o d u c t . T h i s m a t e r i a l was s u p p l i e d b y D r . I . D . S u c k l i n g o f o u r l a b o r a t o r i e s . T h i s m a t e r i a l was s u p p l i e d b y D r . A . Y u e n g o f o u r l a b o r a t o r i e s . - 75 -eforts were not successful. For instance, when the reaction tempera-ture was raised to 0°C, glc analysis of an aliquot of the solution showed an increase in the proportion of product in which E=H. For example, when the experiment summarized in entry 1 was carried out at 0°C instead of at -78°C, the glc ratio of the substiution product to the product in which E=H was approximately 1:1. Furthermore, upon enhancing the nucleophilcity of the anionic intermediate by adding HMPA to the reaction mixture, the proportion of product in which E=H was slightly decreased, but the reactions were not as clean as in the absence of HMPA, and consequently the yields were lower. It should be mentioned that when the experiment summarized by entry 6 was carried out, glc analysis of the solution indicated the presence (up to 10%) of the coresponding product in which E=H. However, upon chromatography of the crude oil on silica gel, the ester (185) was obtained as the sole substiution product. Although the yield of (185) was low, eforts were not made to optimize the reaction conditons. It should be noted that in order to ensure that the transmetalation-alkylation reactions proced in a clean and eficient maner it is imperative to maintain moisture free conditons and to use methylithium of low halide content from a relatively freshly opened botle (up to 1 month old). Al compounds reported in Table VII exhibited H^ nmr, ir and mas spectra in ful acord with the asigned structures. Regardles of the stereochemistry of the alkyl 2,3-bis(trimethyl-stannyl) -2 -alkenoate employed for the transmetalation-alkylation proces, the product posesed the same stereochemistry in both cases. Thus, treatment of THF solutions of (78) or (83) with methylithium, - 76 -followed by alkylation of the resultant intermediate, provided in both cases, a single product in which the ester group and the trimethylstan-nyl group are in a c is relationship. Presumably, transmetalation of (83) and (78) leads, in each case, to the formation of allenoate anions 3 9 (79) , which alkylate from the side opposite the bulky trimethyl-stannyl group, thus affording a single stereoisomer (80) (Scheme 21). Me3Sn SnMe3 Me3Sn OR' Me3Sn C02R' H — > — ( — H R ft, C02R' R » 0 L i R SnMe 83 ' 79 78 Me3Sn CO,R' H R E 80 Scheme 21 However, one might expect a lowering in the stereoselectivity i f the electrophile was s t er i ca l ly undemanding, such as proton. Indeed, when the intermediate resulting from the transmetalation of (124) was protonated, glc analysis of the solution showed the presence of the geometrically isomeric products (196) and (197), in a rat io of 1:8, respectively (equation 29). These latter two products were readily distinguished from each other by analysis of their ^H nmr spectra. E x p l i c i t l y , in each of the ^H nmr spectra, the signal corresponding to the v i n y l i c proton showed sate l l i t e peaks due to tin-proton coupling ( 3 Jg n _jj). The coupling constant associated with this coupling is 72 Hz - 77 -Me3Sn SnMe3 Me3Sn H Me3Sn C02Et H H • H ,29> Me C0 2Et Me C0 2Et Me H 124 196 197 1 8 in compound (196) and 116 Hz in compound (197). Thus, based on the fact that 3J_Sn-H ^ t r a n s ^ > ^J-Sn-H (c i s ) 4 2 , 43a stereochemical configura-t ion of (196) was assigned as (E), whereas (197) was assigned as (Z). Chong, 4 2 had reported a product ratio of 1:9 ((196):(197)) for the transmetalation-protonation of ethyl (E)-2,3-bis(trimethylstannyl)-2-butenoate (77). Up to this point in the discussion no conclusive evidence has been presented regarding the stereochemical configuration assigned to the substitution products (80). However nOe difference experiments on a representative example unequivocally established the stereochemical configuration of these compounds. Thus, in the ^H nmr spectrum of (179), i rradiat ion of the singlet at 6 3.73 (-OMe) caused signal Me3Sn C02Me 179 enhancement of the singlet at 6 0.15 (-SnMe.3), while irradiat ion of the signal at 6 2.45 (-CH2CH3) caused signal enhancement at 6 3.19 (-CH 2CHCH 2), 6 0.93 (-CH 2CH 3) and 6 0.15 (-SnMe.3). Furthermore, i rradiat ion of the singlet at 8 0.15 (-SnMe.3), caused signal enhancement at 6 0.93 (-CH 2 CH 3 ) , 6. 2.45 (-CH 2CH 3) and 6 3.73 (-OMe). - 78 -Since i t seemed l ike ly that the transmetalation of a lkyl 2,3-bis-(trimethylstannyl)-2-alkenoates leads to the formation of allenoate anions, an attempt was made to provide evidence for such allenoate anions. Speci f ical ly , attempts were made to direct ly trap an allenoate anion using various s i l y la t ing agents, such as tert-butyldimethylsi lyl chloride and tert-butyldimethylsi lyl trifluoromethanesulfonate. How-ever, when a solution of ethyl (E)-2,3-bis(trimethylstannyl)-2-butenoate (77) in THF was treated with a solution of methyllithium in ether, followed by the addition of tert-butyldimethylsi lyl chloride or tert-butyldimethylsi lyl trifluoromethanesulfonate at different temper-atures ( - 9 8 ° C , -78°C, - 4 8 ° C ) , no material corresponding to the substituted allene (198) was isolated (equation 30). Although the reactions were not clean, the. predominant material which was identif ied was the corresponding product (197). Furthermore, the i r spectra of the crude o i l s showed no evidence of a carbon-carbon double bond stretching frequency corresponding to an allene function. Me3Sn C0 2Et \ f Me3Sn OEt H 3 - )—( Me SnMe3 or TBDMSQTf Me OSIMe2!Bu 77 198 Interestingly, though, when tr imethyls i ly l chloride was added to a THF solution of the intermediate resulting from the transmetalation of (77) at -98°C, and the reaction mixture was then warmed to -78°C, an unexpected product was formed. After appropriate workup, the latter material was isolated in 70% y ie ld . Analysis of the spectral data indicated that this substance possessed the structure depicted in - 79 -molecular formula (199). For example, the i r spectrum of (199) showed an absorpt ion at 1695 c m ' 1 a t t r i b u t a b l e to the carbonyl s t r e t c h i n g frequency of an a ,^-unsaturated ester func t ion and an absorpt ion at 850 cm" 1 a t t r i b u t a b l e to the s i l i c o n - m e t h y l rock ing frequency of a t r i m e t h y l -s i l y l group. The -^ -H nmr spectrum of (199) cons i s t ed of a 9-proton Me3Sn C02Et H Me SiMe3 199 s i n g l e t at 5 0.15 ( 2 J_sn-H = 5 3 H z ) > a 9-proton s i n g l e t at 6 0.25 ( -S iMe 3 group), a 3-proton t r i p l e t at 6 1.30 (J = 7 Hz) , a 3-proton s i n g l e t at 6 2.22 ( 3J_Sn-H = 5 1 H z ^ a n d a 2 " P r o t o n quartet at 5 4.12 (J = 7 Hz) . Furthermore, h igh r e s o l u t i o n mass spectrometry v e r i f i e d that the mole-c u l a r formula was C ^ r ^ C ^ S ^ 1 1 , Although conc lus ive evidence for the stereochemical c o n f i g u r a t i o n of (199) was not obtained, the assignment was made by analogy to that of compound (179). Moreover, i n the 1 H nmr spectrum of (199) the chemical s h i f t of the v i n y l methyl group i s 5 2.22. I f the es ter func t ion and the methyl group were c i s - r e l a t e d we would expect the corresponding chemical s h i f t of the v i n y l methyl group to be at approximately 5 2.1 ppm (e .g . see entry 1, Table I I I ) . With a seemingly e f f i c i e n t method of generat ing v i n y l s i l a n e s such as (199) at hand, the g e n e r a l i t y of t h i s method was i n v e s t i g a t e d . However, unexpectedly, when the intermediate r e s u l t i n g from the transmeta lat ion of a THF s o l u t i o n of methyl (Z) -2 ,3 -b i s ( t r imethy l s tanny l ) -2 -pentenoate (125) was t rea ted with t r i m e t h y l s i l y l c h l o r i d e at - 9 8 ° C and the r e a c t i o n was warmed to - 7 8 ° C , a s u b s t a n t i a l amount of (201) was formed (equation - 80 -31). Glc analysis of the reaction mixture indicated the presence of an 85:15 mixture of products corresponding to (201) and (200), respectively (equation 31). When the reaction was carefully monitored (glc analysis) Me3Sn SnMe3 Me3Sn C02Me Me3Sn C02Me = J 1.MeLI,THF \ = / \ = / (311 ^ 27TMSC1 f \ + / \ 1 1 C02Me ' SIMe3 ' H 125 200 201 15 85 at different temperatures (-78 6C, -48°C, -20°C, O'C, 25°C) i t was found that the rat io of (200) to (201) remained re lat ive ly unchanged. Further-more, changing the solvent to pentane or to a DME;THF (5:1) mixture did not improve the outcome of the reaction (equation 31). When the reaction was repeated using other alkyl 2,3-bis(trimethylstannyl)-2-alkenoates such as (150) and (153), there was obtained, in each case, a mixture of products analogous to those shown in equation 31, in a similar rat io (glc) . Presumably, when the a lkyl group ( i . e . R group) of Me3Sn C02Me Me,STi C0 2Me M SnMe3 J——' SnMe3 BJMe 2SI0' 1 5 0 r \ 153 the alkyl-2,3-bis(trimethylstannyl)-2-alkenoates becomes s t er i ca l ly more demanding than that of a methyl group (compounds (125), (150) and (153)), .& competition arises between O-s i ly lat ion and C-s i ly la t ion . In these l a t t er cases O-s i ly la t ion would predominate to afford compounds analogous to (198), which, upon exposure to workup conditions would lead - 81 -to the observed products. As such, ethyl 2,3-bis(trimethylstannyl)-2-butenoate (77) was the only compound, which, upon transmetalation-s i l y l a t i o n , gave substantial amounts of v inyls i lane. The transmetalation-alkylation reactions discussed so far in this section have consisted of sequences involving intermolecular alkylation processes. We were also interested in probing the u t i l i t y of the corresponding intramolecular alkylation reactions. In part icular , we f e l t that the transmetalation of methyl (E)- or (Z)-w-halo-2,3-bis(tri-methylstannyl)-2-alkenoates ((202) or (204)), followed by intramolecular alkylat ion of the resultant anions, would lead to the formation of cyc l i c trimethylstannyl a,^-unsaturated esters (203) (equation 32). 202 203 " 204 These lat ter compounds have served as useful intermediates in the development of a new annulation sequence.^3 It was found that when a solution of methyl (Z)-2,3-bis(trimethyl-stannyl) -6-iodo- 2 -hexenoate (139) in THF was treated successively with methyllithium (ether solution) and HMPA (2.3 equiv) at -98°C, and the mixture was then s t i rred at -98°C for 1 h, a single product was formed. After appropriate workup, the latter material was isolated in 73% y i e l d (equation 33). Determination of the structure of this material (205) 139 205 - 82 -was accomplished by analysis of the nmr, i r and mass spectra. For example, the nmr spectrum of (205) showed a 9-proton singlet at S 0.16 (2J.Sn-H " 5 5 H z )> a 2-proton quartet at 5 1.87 (J - 7 Hz), a 4- proton t r i p l e t at 5 2.60 (J - 7 Hz) and a 3-proton singlet at 6 3.70. Furthermore, high resolution mass spectrometry showed that the molecular formula of this material is CioHisC^SJn. The results of using other alkyl w-halo-2,3-bis(trimethylstannyl)-2-alkenoates are summarized in Table IX. It should be noted, that as expected, the stereochemical configuration of the substrate is of no consequence in the cycl izat ion process. For example, compare the experiments summarized in entries 1 and 2. These examples provide further evidence that the reactive intermediates resulting from the chemoselective transmetalation of a lkyl 2,3-bis(trimethylstannyl)-2-alkenoates are allenoate anions. It may also be noted that the yields of the reactions summarized in Table IX are generally good, ranging from 58% to 74%. Although glc analyses of each of the reaction mixtures of the experiments summarized in Table IX indicated the presence of one major component (90%), t i c analyses indicated the presence of polar baseline material corresponding to unidentified polymeric material. As a consequence, the isolated yields of the cyclized compounds (203) in Table IX are not as high as one might expect. Nevertheless, the y i e ld of 58% (entry 6) is good considering the fact that i t reflects the formation of a 7-membered r ing. In contrast, the reactions leading to 5- and 6-membered rings were eff ic ient processes, proceeding in isolated yields of 69-74% (Table IX). A l l the compounds that are summarized in Table IX exhibit ^H nmr, i r and mass spectra in f u l l accord with the - 83 -Table IX: Formation of c y c l i c ^ - t r i m e t h y l s t a n n y l a ,^ -unsatura ted es ters (203) 202 203 204 E n t r y 3 202 204 n X 203 Y i e l d (%) l c 146 - 1 C l 205 69 2 - 138 1 Br 205 74 3 - 139 1 I 205 73 4 - 141 2 Br 206 72 5 - 142 3 I 207 58 React ion c o n d i t i o n s : A s o l u t i o n (THF, - 98 °C ) of (202) or (204) was t rea ted with MeLi (1.2 equiv) and HMPA (2-3 equ iv ) , the r e a c t i o n mixture was s t i r r e d at -98°C f o r 1 h , and then saturated aqueous NH^Cl was added. Y i e l d of p u r i f i e d , d i s t i l l e d product . In t h i s r e a c t i o n , the r e a c t i o n mixture was warmed to - 7 8 ° C . - 84 -assigned structures. It should also be noted that the amide (208) was readily formed in 70% yield from the intramolecular transmetalation-alkylation of (E)-N,N-dimethyl-2,3-bis(trimethylstannyl)-6-bromo-2-hexenamide (175) (equation 34). The spectral data derived from compound (208) are fully in accord with the assigned structure. In summary i t should be pointed out that, in order for the intramo-lecular transmetalation-alkylation reactions to proceed in a clean and efficient manner, i t is imperative to use HMPA. On the other hand, HMPA is not required for the corresponding intermolecular transmetalation-alkylation reactions. B. Synthesis of stereochemically defined trisubstituted vinyl iodides With a facile synthesis of trisubstituted vinylstannanes of general structure (80) at hand, our next objective was to util ize these com-pounds as intermediates for developing a synthetic route to functional-ized, stereochemically defined tetrasubstituted alkenes. An in i t ia l transformation that we envisaged was the manipulation of the ester function of (80) to provide compounds of general structure (85) (W is a (34) 175 208 - 85 -functionalized group derived from the C O 2 R ' moiety) (Scheme 22). In part icular , we envisaged reduction of the ester moiety of substances (80) to the a l l y l i c alcohols (209), which could then, for example, be converted into ethers of general structure (210) (Scheme 22). These lat ter compounds are, of course, equivalent to compounds of general structure (85), in which W - C H 2 0 R " . Me3Sn C02R* Me,Sn w H H R E R E 80 85 Me3Sn / — O H Me3Sn OR" R E R E 209 210 Scheme 22 We were pleased to find that the reduction of the ester function of compounds (80) to the a l l y l i c alcohols (209) was a fac i le process. For example, when a solution of methyl (Z)-2-(2-propenyl)-3-trimethyl-stannyl -2 -pentenoate (179) in diethyl ether was treated with a solution of DIBAL in hexane, and the solution was s t irred at -78°C for 1 h and at 0°C for 1.5 h, t i c analysis of an aliquot showed the presence of a single compound, which was subsequently identif ied as the alcohol (211) (equation 35). After appropriate workup, the alcohol (211) was isolated in a y i e ld of 94%. The spectral data obtained from (211) readily confirmed the structural assignment. For example, the i r spectrum of - 86 -Me3Sn C0 2 Me Me3Sn . — OH DIBAL,Et20 -78° — 0°C (35) 179 21 1 (211) showed a broad absorption at 3348 cm"1 attributable to the 0-H stretch of an alcohol function and an absorption at 769 cm"! attribut-able to the tin-methyl rocking frequency of a trimethylstannyl group. The nmr spectrum of (211) showed the presence of a -CH2OH moiety, which gave r ise to a 1-proton t r ip l e t at J 1.2 (J - 6 Hz) and a 2-proton doublet at S 4.05 (J = 6 Hz). Furthermore, high resolution mass spectrometry showed that the molecular formula was C]^H22OSn. Under a set of conditions identical with those described above, (Z)-4-methyl-2-(propenyl)-3-trimethylstannyl-2-penten-l-ol (212) was prepared in 97% y ie ld from the corresponding methyl ester. It was found that the reduction of the ester moiety of compounds (80) could also be accomplished by using lithium aluminum hydride. However, reaction times were longer and the reactions were not as ef f ic ient as those in which DIBAL was used as the reducing agent. For example, a solution of (189) in diethyl ether was treated with LAH at room temperature and the mixture was s t i rred for 18 h. Tic analysis of the reaction mixture indicated the presence of one major compound (Rf = 212 - 87 -0.25). ( s i l i c a gel , development with 5:1 petroleum ether-diethyl ether) and some polar baseline material. After appropriate workup, the alcohol (213) was isolated in 65% y ie ld (equation 36). It may be noted that Me3Sn Bit* Me2SIO OH C 0 2 E t Me 3 Sn // ^ ... / = \ / Bi/ Me2SIO (36) 1 89 2 1 3 (213) is a trans - 2-butene-1.4-diol derivative in which one of the hydroxyl groups is protected. The spectral data obtained from (213) was found to be In complete agreement with the structural assignment. Under a set of reaction conditions similar to those describing the LAH reduction of compound (189), the alcohol (214) was prepared in 68% from the corresponding methyl ester. The spectral data obtained from (214) was found to be in complete agreement with the assigned structure. The conversion of the alcohol moiety of compound (211) into a methoxymethyl ether was readily accomplished. Thus, a solution of (Z)-2-(2-propenyl)-3-trimethylstannyl-2-penten-l-ol (211) in C H 2 C I 2 was treated with N,N-diisopropylethylamine and methoxymethyl c h l o r i d e 6 4 and the solution was s t i rred at room temperature for 3 h. Glc analysis of the reaction mixture indicated the presence of a new component, which was subsequently identi f ied as the ether (215). After appropriate - 88 -workup, the ether (215) was isolated in 79% y ie ld (equation 37). The spectral data obtained from (215) readily confirmed the structural assignment. For example, the i r spectrum of (215) showed an absorption at 1152 cm"1 attributable to the C-O stretch ©f an ether function. The nmr spectrum of (215) c learly showed ±he presence of a -CH2OCH2OCH3 moiety, which gave rise to a 3-proton s inglet at S 3.38, a 2-proton singlet at S 3.96 ( 4 « I s n - H *" 1 0 Hz) and a 2-proton singlet at 6 4.62. Furthermore, high resolution mass spectrometry showed that the molecular formula was C^3H2502Sn. Me3Sn —OH Me3Sn —OMOM 211 215 Compound (215) represents a potential ly useful intermediate. Conceivably, transmetalation of (215) with an alkyll i thium reagent would afford a vinyl l i thium species (216), which could react with a variety of electrophiles to afford tetrasubstituted alkenes (217). Alternatively, these lat ter compounds could be formed by the Pd(0)-catalyzed cross-coupling reaction of (215) with a variety of organic electrophiles (equation 38). (38) 215 217 216 - 89 -However, a l l attempts to effect clean transmetalation of (215) with different alkyl l i thium reagents, under a variety of conditions, met with fa i lure . For example, a solution of (215) in THF was treated succes-sively with methyllithium (ether solution) and HMPA (30 equiv) at -78°C, and the mixture was s t irred at -78°C for 1 h. After the mixture was quenched with saturated aqueous ammonium chloride, glc and t i c analyses of the reaction mixture indicated the presence of only one compound (215). Moreover, upon workup, 67% of the latter material was recovered. Similarly , when the transmetalation reaction was repeated using n-butyl-lithium or sec-butyllithium in the absence of HMPA, approximately 65% of (215) was recovered in each case. Furthermore, when the reaction was repeated using sec-butyllithium in solvent mixtures comprised of THF and HMPA (8:1 to 3:1) at -78°C, numerous unidentified components including the vinylstannane (215) were detected (glc and t i c analyses). Presumably, the s ter ica l ly hindered nature of the trimethylstannyl group is primarily responsible for the fact that the transmetalation process is very sluggish (equation 39) .^a>^^ S t i l l e and coworkers^ have reported that the Pd(O)-catalyzed cross-coupling reaction of vinylstannanes with a l l y l i c halides is a fac i le process. Since we were not successful in effecting clean transmetala-t ion of compound (215) the Pd(0)-catalyzed cross-coupling reaction ( 3 9 ) - 90 -between (215) and 3-iodo-2-methylpropene was investigated. Unfortu-nately, a l l attempts to effect coupling between these substances fa i led (equation 40). For example, when (215) and 3-iodo-2-methylpropene were (40) added to a solution of palladium(II) acetate, triphenylphosphine and triethylamine-*-* in CH3CN and the mixture was s t irred at 85°C for 24 h, 82% of the vinylstannane remained in solution (glc analysis). When the reaction was repeated in CH3CN using bis(dibenzylideneacetone)palla-dium(O)^ and triphenylphosphine numerous unidentified components were detected (glc and t i c analyses). However, the major component (36% by glc analysis) was subsequently identif ied as the coupled product (218) and was isolated in approximately 10% y ie ld . Efforts to increase the y i e ld by using different solvents (THF or DMF) were not successful. It should be mentioned that the Pd(0)-catalyzed cross-coupling reaction was also attempted with other vinylstannanes such as (179) and (211) using v iny l hal ides 2 ^ and v iny l t r i f l a t e s 2 ^ such as bromoethylene and 3-methyl-1-trifluoromethanesulfonyloxycyclohexene. However, these 179 211 - 91 -la t ter reactions resulted in the formation of mixtures containing numerous unidentified components. Although the transmetalation and Pd(0)-catalyzed cross-coupling reactions were not successful with the vinylstannane (215), we fe l t that an alternative route for forming tetrasubstituted alkenes could be u t i l i z e d . In part icular , we envisaged that vinylstannanes of general structure (80) could be converted into the corresponding v iny l iodides (219) (equation 41), since numerous reports in the l i t e r a t u r e 1 have shown that the process is smooth and eff ic ient . Indeed, when a solution of the alcohol (211) in CH2CI2 was treated with i o d i n e 6 7 at room temperature, t i c analysis of the pale yellow solution indicated the presence of one major component along with some polar baseline material. After appropriate workup, the iodide (220) was isolated in 63% y ie ld (equation 42). The spectral data obtained from (220) confirmed the structural assignment. For example, the nmr spectrum of (220) consisted of a 3-proton t r ip l e t at 6 1.07 (J - 7.5 Hz), a 1-proton (42) 2 1 1 2 2 0 - 92 -t r i p l e t at f 1.64 (J = 6 Hz), a 2-proton quartet at S 2.61 (J - 7.5 Hz), a 2-proton dt at 8 3.09 (J •= 6, 1.5 Hz), a 2-proton doublet at 5 4.24 (J - 6 Hz), a 1-proton ddt at 6 5.06 (J - 10, 2, 1.5 Hz), a 1-proton ddt at 6 5.08 (J - 17, 2, 1.5 Hz), and a 1-proton ddt at 8 5.76 (J = 17, 10, 6 Hz). Furthermore, high resolution mass spectrometry showed that the molecular formula of compound (220) is CgH^OI. The stereochemical configuration of compound (220) was assumed to be as shown, since the iododestannylation reaction occurs with retention of c o n f i g u r a t i o n . 6 ® Conversion of the alcohol (220) into the corresponding methoxyeth-oxymethyl e t h e r , 6 9 was readily accomplished by treating a solution of (220) in CH2CI2 with N,N-diisopropylethylamine and 2-methoxyethoxymethyl chloride. Glc analysis of an aliquot of the solution showed the presence of a single compound, which was subsequently identif ied as the ether (221). After appropriate workup, the ether (221) was isolated in 88% y ie ld . The spectral data obtained from (221) confirmed the structural assignment. For example, the i H nmr spectrum (which is depicted In F ig . 7) showed the presence of a -CH2OCH2OCH2CH2OCH3 moiety which gave r ise to a 3-proton singlet at S 3.41, a 2-proton multiplet at 4" 3.55-3.61, a 2-proton multiplet at S 3.72-3.77, a 2-proton singlet at 8 4.22 and a 2-proton singlet at 8 4.75. Furthermore, high resolution mass spectrometry ver i f ied that the molecular formula of (221) is O O 221 - 94 -C12 H21 ° 3 I • By u t i l i z i n g a sequence of steps similar to those just described, the ether (223) was prepared from the alcohol (212) (equation 43). The spectral data obtained from compounds (222) and (223) were found to be in f u l l accord with the structural assignments. The u t i l i t y of compounds (221) and (223) as key intermediates for the synthesis of functionalized, stereochemically defined, tetrasubsti-tuted alkenes w i l l be discussed in the following section of this thesis. In the meantime, alternative transformations of the alcohol moiety of compounds of general structure (224) w i l l be discussed. For instance, a poss ib i l i ty that we envisaged was the conversion of the alcohol function of (223) into an aldehyde moiety, which could then be treated with a Wittig reagent to afford substituted dienes of general structure (225) (equation 44). Indeed, i t was found that when a solution Me3Sn .— QH OMEM (43) 212 222 \ 223 (44) R E R E 224 225 of pyridinium chlorochromate, sodium acetate and the alcohol (220) in CH2CI2 was s t i rred for 1 h 45 min, t i c analysis of an aliquot indicated - 95 -the presence of only one component (Rf •» 0.77) ( s i l i c a gel, development with 7:3 petroleum ether-ethyl ether), which was subsequently identif ied as the aldehyde (226). After appropriate workup, the aldehyde (226) was isolated in 82% y ie ld (equation 45). The spectral data obtained from (226) c learly showed the presence of an aldehyde function. For example, the Ir spectrum showed an absorption at 2859 cm"1 attributable to the aldehyde carbon-hydrogen stretching frequency and an absorption at 1729 cm"1 attributable to the carbonyl stretching frequency of the aldehyde function. Moreover, the 1 H nmr spectrum of (226) showed a 1-proton singlet at 6 9.04. In addition, high resolution mass spectrometry ver i f i ed that the molecular formula of (226) is CgH^OI. H (45) 220 226 The subsequent conversion of (226) into the corresponding diene was readily accomplished. Thus, when the aldehyde (226) was added to a solution of methylenetriphenylphosphorane in THF and the solution was s t i rred at room temperature for 2 h, t i c analysis of the reaction mixture indicated the presence of a single UV active component (Rf -0.66) ( s i l i c a gel , development with 95:5 petroleum ether-diethyl ether), which was subsequently identif ied as the triene (227). After appropriate workup, the triene (227) was isolated in 78% y i e l d . The spectral data of this material was found to be in f u l l accord with the assigned structure. For example, the "^H nmr of (227) showed a 3-proton - 96 -t r i p l e t at S 1.12 (J - 7.5 Hz), a 2-proton quartet at 6 2.72 (J - 7.5 Hz), a 2-proton dt at 6 3.15 (J - 6, 1.5 Hz), a 1-proton ddt at 6 5.02 (J - 10, 2, 1.5 Hz), a 1-proton ddt at S 5.04 (J = 17, 2, 1.5 Hz), a 1-proton doublet at 5 5.16 (J - 11 Hz), a 1-proton doublet at S 5.29 (J = 17 Hz), a 1-proton ddt at 6 5.76 (J = 17, 10, 6 Hz), and a 1-proton dd at 5 6.69 (J = 17, 11 Hz). Furthermore, high resolution mass spectrometry ver i f i ed that the molecular formula of (227) is C9H13I . By u t i l i z i n g a series of steps similar to those that have been discussed up to this point in the thesis, the tetraene (230) was synthesized (Scheme 23). The synthesis of (230) was accomplished according to the following sequence. Reduction of the ester function of (195) with a solution of DIBAL in hexane, afforded the alcohol, which, without puri f icat ion , was converted direct ly into the corresponding iodo alcohol (228) (isolated y ie ld -67%). Oxidation of this lat ter material afforded a 91% y ie ld of the aldehyde (229) , which was treated with methylenetriphenylphosphorane to afford, in 89% y ie ld , the corresponding tetraene (230). It should be noted that the spectral data of the compounds shown in Scheme 23 were found to be in f u l l accord with the assigned structures. For example, the i r spectrum of compound (228) showed a broad absorption at 3332 cm"l attributable to the 0-H stretching frequency of an alcohol function. On the other hand, the i r - 97 -195 228 PCC.NaOAc, CH2CI2 H 230 Ph 3P=CH 2 THF 229 Scheme 23 spectrum of (229) showed an absorption at 1680 cm"1 attributable to the carbonyl stretching frequency of an enal function. The nmr spectrum of compound (230) c learly showed the presence of a conjugated v iny l moiety, which gave a 1-proton dd at S 5.18 (J — 11, 0.5 Hz), a 1-proton dd at 6 5.30 (J = 17, 0.5 Hz) and a 1-proton dd at S 6.70 (J - 17, 11 Hz). Furthermore, high resolution mass spectrometry of compounds (228), (229) and (230) ver i f ied that the molecular formulas are C10H15^1> ^11^13^1 a n d ^11^15l' respectively. The poss ib i l i ty of transforming alcohols of general structure (224) into the corresponding halides (231) (X — halogen) was also considered (equation 46). It was fe l t that substances (231), which are potentially synthetically equivalent to the d,a synthons (232), could be useful for the development of annulation sequences.3** We were pleased to f ind that - 98 -(46) the transformation (equation 46) was readily accomplished. For example, when a solution of the alcohol (212) in CC1 4 was treated with triphenyl-phosphine and tr iethylamine 7 0 and the solution was refluxed for 12 h, t i c analysis of the reaction mixture showed the presence of one major component (Rf — 0.55) ( s i l i c a gel, development with 95:5 petroleum ether-diethyl ether), which was subsequently identif ied as the chloride (233). After appropriate workup, the chloride (233) was isolated in 91% y i e l d . Treatment of a solution of this compound in CH2CI2 with iodine afforded the corresponding iodide (234) in an isolated y ie ld of 95% (equation 47). The spectral data of compounds (233) and (234) were (47) readily interpreted and were found to be in f u l l accord with the assigned structures. For example, the nmr spectrum of (234) showed a 6-proton doublet at 6 0.95 (J - 7 Hz), a 1-proton septet at 6 2.35 (J -7 Hz), a 2-proton dt at £ 3.15 (J - 6, 1.5 Hz), a 2-proton singlet at 6 4.30, a 1-proton ddt at 6 5.05 (J = 17, 2, 1.5 Hz), a 1-proton ddt at 6 5.10 (J - 10, 2, 1.5 Hz) and a 1-proton ddt at 5 5.77 (J — 17, 10, 6 - 99 -Hz). Furthermore, high resolution mass spectrometry ver i f ied that the molecular formula of (234) is CgH^ClI . It was found that when solutions of alkyl 2,3-bis(trimethylstannyl)-2- alkenoates in CH2CI2 were treated with iodine, some unexpected compounds were formed. For example, a solution of ethyl (Z)-2,3-bis-(trimethylstannyl)-2-butenoate (124) in CH2CI2 was treated with a solution of iodine in CH2CI2 at -78°C and the purple mixture was s t i rred at -78°C for 30 min. Tic and glc analyses of the reaction mixture indicated the presence of two components, one of which was found to correspond to trimethylstannyl iodide. The other component, which was isolated in 91% y ie ld , was subsequently identif ied as ethyl (Z)-2-iodo-3- trimethylstannyl-2-butenoate (235) (equation 48). The spectral data Me3Sn SnMe3 Me3Sn I y=^ I 2 , C H 2 C I 2 S ) = = ^ ( 4 8 ) Me C0 2 Et " ? 8 C Me C0 2 Et 124 235 obtained from (235) clearly established the constitution and stereo-chemical configuration. For example, the i r spectrum showed an absorp-t ion at 1719 cm"1 attributable to the carbonyl stretching frequency of an a,B-unsaturated ester function. The ^H nmr spectrum of (235) consisted of a 9-proton singlet at S 0.32 (2J_Sn-H " -*6 Hz), a 3-proton t r i p l e t at 6 1.32 (J - 7 Hz), a 3-proton singlet at 6 2.10 (3J_Sn-H " 4 5 Hz) and a 2-proton quartet at 6* 4.25 (J - 7 Hz). The important piece of ^H nmr data to note is the ~*J_Sri-H v a l u e Hz) associated with the v iny l methyl group, which unequivocally established the regiochemistry - 100 -of the product to be as depicted by s t ruc ture (235). The other r e g i o -isomer would invo lve a 4J_sn-H which would be much smal ler than 45 Hz. F i n a l l y , h igh r e s o l u t i o n mass spectrometry v e r i f i e d that the molecular formula of (235) i s C 9H 1 702lSn2. The stereochemical c o n f i g u r a t i o n of (235) was corroborated by performing nOe d i f f e r e n c e experiments. Thus, i r r a d i a t i o n of the s i g n a l at 5 0.32 (-SnMe.3) caused s i g n a l enhancement at S 2.10 ( v i n y l methyl ) , whi le i r r a d i a t i o n of the s i g n a l at 6 4.25 (-OCH2CH3) caused s i g n a l enhancement at 6 2.10 and 8 1.32 ( -OCH 2 CH 3 ) . The r e s u l t s of t h i s nOe d i f f e r e n c e experiment confirmed that the t i n - i o d i n e exchange process occurred with r e t e n t i o n of s tereochemistry , as one would expect based on l i t e r a t u r e precedent.*"** I t i s i n t e r e s t i n g to note , i n the nmr spectrum of (235), the e f f e c t of the e lec t ronegat ive iod ine atom. For example, the chemical s h i f t of the v i n y l i c carbon a to the es ter f u n c t i o n i n (235) i s 6* 93.6, compared to 6 149.9 i n the s t a r t i n g mate r ia l (124). Under a set of cond i t ions s i m i l a r to those descr ibed above, methyl (Z ) -2 - iodo-3 - t r imethy ls tanny l -2 -pentenoate (236) was prepared i n 97% y i e l d from the corresponding b i s ( t r i m e t h y l s t a n n y l ) a.^-unsaturated e s t e r . Iododestannylat ion reac t ions (equation 49) have been the subject of i n t e n s i v e mechanist ic s tud ies dur ing the past three decades.71-73 C02Me 2 3 6 - 101 -R ' — S n R 3 + l 2 • R'l + ISnR3 (49) Electrophi l ic attack of the halogen molecule on the carbon bearing the tr ia lkylstannyl group is the recognized mode of reaction.71-73 j t ^as been found that different groups on t i n are cleaved by iodine with different rates. Thus, i f one considers an organotin compound contain-ing three a lkyl groups (e.g. n-butyl) and a fourth group, then the ease of cleavage by iodine follows the sequence benzyl > aryl ~ v iny l > methyl > higher a l k y l . F o r mixed te tra-a lky l t in compounds the reaction can occur either with retention or inversion of configuration in an a lkyl group (R' in equation 49), depending on the nature of the a lkyl groups on t i n and of the so lvent .^ For v inyl t r i a l k y l t i n compounds (R' in equation 49 is an alkenyl group), the reaction always CO occurs with retention of configuration in the alkenyl group . 0 0 The mechanism of the iododestannylation reaction is s t i l l the subject of controversy, largely revolving around the depiction of the transit ion state. A charge-transfer mechanism^0 or a cyc l ic or an open S£2 transit ion state^ 2-75 j i a s been proposed to account for the observed se lect iv i ty in te tra-a lky l t in compounds. In many cases an open Sg2 transit ion state (237), which can lead to inversion or retention of configuration, appears to be favoured when the solvent is the strongest nucleophile present (e.g. I 2 in methanol).^2•75 Qn the other hand, i f a portion of the iodine reagent is the strongest nucleophile present (e.g. I 2 i n C C I 4 ) , the reaction apparently involves a cyc l i c S£2 transit ion state (238), which always leads to retention of configuration.^2.75 Nasie lski 0 ^ and coworkers have proposed a transit ion state shown in - 102 -.Sn • I — I ••solvent 237 \ 1.* • • • * 238 (239) to account for the retention of stereochemistry observed in the iododestannylation of v inyl t r i a l k y l t i n compounds, when the reaction is carried out in a polar solvent such as methanol. In this case the solvent assists in the cleavage of the carbon-tin bond. / \ / •• a* ' a". SnR, 239 H .OCH 3 A possible transit ion state that accounts for the chemo- and stereoselective iododestannylation of a lkyl (Z)-2,3-bis(trimethyl-stannyl)-2-alkenoates, and that is in accord with those reported in the l i t e r a t u r e 7 4 ' 7 5 > 7 7 i s shown in (240). Presumably, the chemoselectivity arises from the fact that, of the two v iny l i c carbons, the carbon a to the ester function is more able to bear a developing negative charge, since i t can be stabi l ized by the ester function. As a consequence, the a-carbon becomes more susceptible to e lectrophi l ic attack by the iodine molecule. Moreover, the cleavage of the carbon-tin bond a to the ester function is now fac i l i ta ted by the nucleophilic portion of the iodine molecule interacting with the electropositive t i n atom. - 103 -R Me3Sn C-TTT:C I SnMe3 2 4 0 Interestingly, though, when an alkyl (£)-2,3-bis(trimethylstannyl)-2-alkenoate was treated with Iodine, a different type of compound was formed as compared to that obtained from the corresponding (Z) Isomer. For example, when a solution of methyl (E)-2,3-bis(trimethylstannyl)-2-pentenoate (147) in C H 2 C I 2 was treated with iodine at room temperature, and the mixture was stirred for 30 min, tic analysis of the yellow reaction mixture did not show the presence of a distinct compound, even when developing solvents of different polarities were used. However, glc analysis of the reaction mixture showed the presence of a new component with a retention time longer than that of (147). This material was subsequently identified as methyl (E)-3-(iododimethyl-stannyl)-2-trimethylstannyl-2-pentenoate (241), and, after appropriate workup, was isolated in 85% yield (equation 50). The spectral data obtained from (241) clearly confirmed the structural assignment. For example, the i r spectrum showed an absorption at 1636 cm"1 attributable (50) - 104 -to the carbonyl stretching frequency of an a,^-unsaturated ester function. The nmr spectrum of (241) consisted of a 9-proton singlet at 5 0.29 ( 2 J .s n -H = 5 5 H z ) • a 6-proton singlet at 5 0.95 ( 2J_s n-H " 6 6 Hz), a 3-proton t r i p l e t at S 1.03 (J - 7 Hz), a 2-proton quartet at 6 2.85 (J - 7 Hz, 3J_Sn-H ~ 9 0 H z ^ a n d a 3 - P r o t o n singlet at S 3.84. Furthermore, high resolution mass spectrometry ver i f i ed that the molecular formula of (241) is C_]H2302lSn2. The iododimethylstannyl group of (241) was shown to be B to the ester function on the basis of the following spectral evidence. In the nmr spectrum of (241) the 3 J S n . H value associated with the v iny l methyl group is 90 Hz, compared to a typical value of 55 Hz in an alkyl 2,3-bis(trimethylstanhyl)-2-alkenoate. This increase of the 3 J_s n .H i - s in accord with a recent l i terature r e p o r t , ^ which states that such an increase is apparent upon substitution of a methyl group on t i n by iodine. Moreover, in the i r spectrum of (241), the carbonyl stretching absorption of the ester function appears at 1636 cm'^, while, in compound (147), the corresponding absorption appears at 1685 cm'^. Such a marked decrease in frequency can be attributed to intramolecular coordination at t i n by the carbonyl oxygen. This coordination would be fac i l i t a t ed by the presence of the iodide atom, since, due to i ts inductive effect, the B-tin atom of (241) would be more e lectrophi l ic than that of (147). The effect of intramolecular coordination at t i n by oxygen is also evident In the * 3 C nmr spectra of (241). For example, the chemical shift of the carbonyl carbon of (241) i s S 193.6, compared to 6 185.6 for the carbonyl carbon of (147). The type of coordination (depicted in (241A)) is in accordance with l i terature reports,^ 9 which - 105 -indicate that intramolecular coordination at t i n by oxygen can only occur to any appreciable extent v ia a 5-membered ring. The formation of compound (241) represents an example of a complete reversal in selectively in the iododestannylation of a 'mixed' tetra-, 0 . 241 A organotin compound. That i s , an alkyltin-carbon bond was cleaved in preference to a vinyltin-carbon bond. This reversal of se lect iv i ty has recently been r e p o r t e d ® 0 to occur in a structurally similar compound (242). Thus, treatment of a solution of (242) in C D C I 3 with iodine afforded the corresponding compound (243) in approximately 80% yie ld (equation 51). A geometric argument was used to explain these results . aSnBu3 / " \ ^ ! n n .M Q " ^y ^ t , 3 ^ - * \ ^ S n B u 2 l (51) C02Me ' ^ "C02Me 242 243 It was argued that intramolecular assistance at t i n by oxygen, during the approach of iodine to carbon, can occur in the transit ion state (depicted in (244)), v i a formation of a 5-membered r ing . This coordina-t ion constrains the v iny l carbon linked to t i n to be In the equatorial posit ion and the carbon of an alkyl group to be in an apical posit ion. Thus, the a lkyl group becomes susceptible to e lectrophi l ic attack (see - 106 -R —• I — I # OMe 244 (244)), which results in the preferential cleavage of the alkyl-tin bond. We feel that the reversal of selectivity observed in the iodode-stannylation of compound (241) can also be rationalized by invoking a geometric argument similar to that discussed above. As a consequence, the process most likely occurs via a transition state analogous to that depicted in (244). Presumably, the low yields of 60-75% observed for the iododestanny-lation of compounds of general structure (209) can be rationalized by a competing pathway involving intramolecular coordination at tin by oxygen. Such a rationale is borne out experimentally, since tic analysis of reaction mixtures involving treatment of (209) with iodine R E 209 showed evidence of polar baseline material. Moreover, upon completion of the reactions, the solutions were yellow. These latter two observa-tions are identical with those evident in the iodination of compound - 107 -(147) (equation 50). This is in contrast to the iododestannylation of compounds such as (124) and (233), in which the yields were >90%. In these cases, no polar baseline material was evident ( t ic analysis) and the solutions were pale purple upon completion of the reaction. Me3Sn SnMe, H Me C0 2Et 1 24 With a fac i le synthesis of v iny l iodides such as (235) and (236) at hand, a br ie f study was in i t ia ted to determine their synthetic u t i l i t y . In part icular , we envisaged reduction of the ester moiety of (245) to afford the corresponding alcohols, which could then be converted into ethers (246). Thus, i t may be noted that the ethers (246) are potential ly synthetically equivalent to the d,d synthons (247), in which the two donor centres are cis-related (equation 52). I f the two donor 245 246 247 centres in (246) could be selectively and successively deployed to afford vinyl l i thium species, which could then react with appropriate electrophiles, a synthesis of stereochemically defined tetrasubstituted alkenes would have been real ized. We were pleased to find that when a solution of (236) in ether was - 108 -t r e a t e d wi th DIBAL at - 7 8 ° C and the mixure was s t i r r e d at - 7 8 ° C for 1 h and at 0°C for 1 h , the a l c o h o l (248) was i s o l a t e d i n 85% y i e l d a f t e r appropriate workup (equation 53). I t should be noted that (248) i s (53) thermal ly unstable , s ince , upon g lc a n a l y s i s , extensive decomposition i s ev ident . The s p e c t r a l data der ived from (248) were found to be i n f u l l accord with the assigned s t r u c t u r e s . For example, the i r spectrum of (248) showed a broad absorpt ion at 3349 cm" 1 a t t r i b u t a b l e to the O-H s t r e t c h i n g frequency of an a l c o h o l func t ion . The ^H nmr spectrum of (248) showed a 9-proton s i n g l e t at 5 0.90 ( 2 J_sn-H = ^ ' a 3-proton t r i p l e t at S 1.16 (J = 7 Hz) , a 1-proton t r i p l e t at 6 1.54 (J = 6 Hz) , a 2-proton qt at 6 2.23 (J = 7, 1.5 Hz) , a 2-proton dt at 5 4.26 (J = 6, 1.5 Hz) . Furthermore, h igh r e s o l u t i o n mass spectrometry v e r i f i e d that the molecular formula of (248) i s CgH^702lSn. Unfor tunate ly , attempts to convert the a l c o h o l (248) in to a c o r r e -sponding ether f a i l e d . Various condi t ions were i n v e s t i g a t e d . These inc luded 2-methoxyethoxymethyl c h l o r i d e , N ,N-d i i sopropy le thy lamine , CH2CI2,6 9 methoxymethyl c h l o r i d e , N ,N-d i i sopropy le thy lamine , CH2CI2,64 t e r t - b u t y l d i m e t h y l s i l y l c h l o r i d e , imidazole , CH2CI2,81 t e r t - b u t y l d i -m e t h y l s i l y l t r i f luoromethanesul fonate , 2 , 6 - l u t i d i n e , CH2CI2®2, d ihydro-pyran, p y r i d i n i u m p.-toluenesulphonate, CH2CI2®3 and t e r t - b u t y l d i m e t h y l -s i l y l c h l o r i d e , l i t h i u m s u l f i d e , CH3CN®4. The only product that was - 109 -isolated in most cases was the coresponding acetylenic ether. Although the formation of compounds of general structure (246) was not realized, additonal work in this area is required. C. Synthesi  of functionalized stereochemicaly defined tetrasubsti- tuted alkenes The vinyl iodides (249), which were prepared as described in the previous section, represent potentialy useful intermediates since presumably, treatment of such compounds with an alkylithium reagent should result in the formation of the coresponding vinylithium species (250). Conceivably these later species, upon treatment with appropri-ate electrophiles, should aford the coresponding fuly substiuted alkenes (251) (equation 54 ) . Thus, it may be noted that the vinylith-ium species (250) would then be syntheticaly equivalent to the d-synthon represented by structure (252). (54) 252 The proces of lithium-iodine exchange' is analogous to the lithium-tin exchange (transmetalation proces) which was discused in - 110 -the general introduction. For instance, the reaction is reversible, leading to an equilibrium mixture favouring the more stable organolith-ium species. Moreover, the lithium-iodine exchange has been assumed to proceed through a four-centred transit ion state (253) . 7 b R L I I R 253 It was thus our intention to find the appropriate experimental conditions under which the vinyl l i thium species (250) could be generated. After some experimentation with the iodide (221), i t was found that conditions that cleanly produced the corresponding l i t h i o species involved treatment of a THF solution of (221) with 2.2 equiv of n-butyllithium at -78°C for 15 min. When the lat ter solution was quenched with saturated aqueous ammonium chloride, glc analysis of the solution showed the presence of a 1:1 mixture of two compounds, the diene (254) and the hydrocarbon n-octane (equation 55). On the other (55) hand, when the reaction was repeated employing only 1.1 equiv of n-butyllithium, glc analysis of the quenched (saturated aqueous ammonium chloride) solution showed the presence of a 9:1 mixture of two com-- I l l -pounds, the dienes (254) and (255), respectively (equation 56). As a consequence, in order to avoid the presence of n-butyl iodide in the reaction mixture, most of our experiments were done with 2.2 equiv of n-butyllithium. Direct alkylation of the vinyl l i thium reagents derived from lithium-iodine exchange of the v iny l iodides (249), proceeded in a smooth fashion to afford the stereochemically homogeneous tetrasubstituted alkenes (entries 1-6, Table X) as the sole substitution products. For example, a solution of the vinyl l i thium reagent in THF, derived from the v iny l iodide (221), was treated with l-bromo-3-methyl-2-butene at -78°C and the mixture was s t irred at -78°C for 30 min. After the mixture had been quenched with saturated aqueous ammonium chloride, t i c analysis indicated the presence of one major component (Rf — 0.33) ( s i l i c a gel, development with 4:1 petroleum ether-diethyl ether). The lat ter material was isolated in 67% y ie ld and was subsequently identif ied as ( Z ) - 5-ethyl-4-(2-methoxyethoxy)methoxymethyl-8-methyl-1,4,7-nonatriene (256) (equation 57). The structure of (256) was ver i f i ed by analysis of the ^H nmr data. For example, in addition to the signals due to the CH2OMEM, a l l y l , and ethyl groups, there appeared two 3-proton singlets at 5 1.67 and S 1.69, a broad 2-proton doublet at J 2.83 (J = 7 Hz) and - 112 -Table X: Preparation of v i n y l l i t h i u m species and t h e i r reactions with e l e c t r o p h i l e s W 249 Jtt-BuLl THF LI W E' W 251 Entry' 249 W E'XC 251 Y i e l d (%) c 221 Et CH2OMEMa Mel 257 93 221 Et CH2OMEMd Me2C-CHCH2Br 256 67 221 Et CHoOMEM" n-BuI 255 65 221 Et CH2OMEMd C1(CH 2) 5I 258 72 227 Et CH=CH2 n-BuI 259 54 230 CH2=CHCH2CH2 CH=CH2 CH 2=CH(CH 2) 3I 260 67 Reaction conditions: A s o l u t i o n (THF, -78°C) of (249) was treated with n-BuLi (1.1 or 2.2 equiv), the re a c t i o n mixture was s t i r r e d at -78°C (10-15 min), the a l k y l a t i n g agent E'X was added, the re a c t i o n mixture was s t i r r e d at -78°C (10 min-2 h) and quenched (NH4CI-H2O) or warmed to 25°C (30 min-7 h) and quenched (NH^Cl-^O). These materials were passed through a column of a c t i v i t y I basic alumina immediately p r i o r to use, except f o r l-bromo-3-methyl-2-butene (entry 2), which was d i s t i l l e d immediately p r i o r to use. c Y i e l d of p u r i f i e d , d i s t i l l e d product. d MEM = CH2OCH2CH2OMe. - 113 -(57) a one proton multiplet in the region 5 4.95-5.05. Furthermore, high resolution mass spectrometry ver i f ied that the molecular formula of (256) is C 1 7 H 2 9 0 3 . S imilarly , when a solution of the vinyl l i thium reagent in THF, derived from the v iny l iodide (221), was treated with iodomethane at -78°C and the mixture was s t irred at -78°C for 10 min, the alkene (257) (entry 1, Table X) was isolated in 93% yie ld after appropriate workup. The spectral data obtained from (257) were found to be in f u l l accord with the assigned structure. When less reactive halides such as n-butyl iodide (entry 3) and 5-chloro-l-iodopentane (entry 4) were employed, the reaction mixtures were warmed to room temperature to ensure complete reaction. The alkenes formed from the experiments summarized in entries 3 and 4, (255) and (258), were isolated in yields of 65% and 72%, respectively. The spectral data of the latter two compounds are fu l ly in accord with the assigned structures (Table X). The ^H nmr spectrum of (258) is depicted in F ig . 8. The formation of tetrasubstituted alkenes from the corresponding iodides (249), in which W - CH=CH2, was also found to be a fac i le process. For example, treatment of a solution of the triene (227) in THF with 1.1 equiv of n-butyllithium at -78°C, followed by addition of - 115 -n-butyl iodide and warming of the reaction mixture to room temperature, afforded the triene (259) in an isolated y ie ld of 54% (equation 58). The spectral data derived from (259) were found to be in f u l l accord 1.n-BuLi(1.1eq),THF / / 2.Q-Bul,-78° — 2 5 ° C Bu / ( 5 8 ) 227 259 with the assigned structure. For example, the •'•H nmr spectrum of (259) showed, in addition to the signals due to the ethyl and a l l y l groups, a 3-proton t r i p l e t at 6 0.92 (J - 7 Hz), a 4-proton multiplet in the region S 1.26-1.44, a 2-proton t r ip l e t at S 2.19 (J - 7 Hz), a 1-proton dd at 6 4.98 (J - 10, 1.5 Hz), a 1-proton dd at 5 5.14 (J - 17, 1.5 Hz) and a 1-proton dd at 6 6.73 (J = 17, 10 Hz). Furthermore, high resolution mass spectrometry ver i f ied that the molecular formula of (259) is C 1 3 H 2 2 . S imilarly , the pentaene (260) was obtained from the iodide (230) by alkylat ion of the corresponding vinyl l i thium reagent with 5-iodo-l-pentene. In this reaction, glc analysis of the crude product showed the presence of 10%'of the corresponding product (261). However, careful d i s t i l l a t i o n of the crude o i l afforded the pentaene (260) in 67% y ie ld . It should be noted that this latter compound is structural ly interest-ing, since, as one moves around the central double bond in a clockwise fashion beginning at the v iny l group, each successive group possesses an additional carbon atom. As expected, the ^H nmr spectrum of (260) is very complex and consists of multiplets corresponding to the methylene - 116 -protons and v iny l i c protons. Nevertheless, the spectral data derived from (260) were found to be in f u l l accord with the assigned structure. Interestingly, when a THF solution of the vinyl l i thium species (262), derived by treatment of the corresponding iodide (221) with 2.2 equiv of n-butyllithium, was treated with 3-iodo-2-methylpropene, the iodide (221) was returned (93%) v ia a "reverse" lithium-iodine exchange (equation 59). Presumably, the greater s tab i l i ty of the a l ly l l i th ium (59) 2 6 2 2 2 1 species, compared to that of the vinyl l i thium species (262) drives the equilibrium to the r ight , thus returning the v iny l iodide (221). However, this problem was readily overcome by treating the vinyl l i thium species (262) with 1 equiv of cuprous(I) bromide•dimethyl sulfide complex at -48°C to afford the corresponding vinylcopper(I) species (263). When this lat ter reagent was treated with 3-iodo-2-methylpropene at -48°C and the mixture was s t irred at -48°C for 45 min, glc analysis of the solution indicated the presence of a minor amount (7%) of the product (254) and a major amount (86%) of the coupled product (266). - 117 -Column chromatography of the crude o i l on s i l i c a gel afforded the alkene (266) in an isolated y ie ld of (69%) (equation 60). The spectra derived i from (266) were found to be in f u l l accord with the assigned structure. (60) 263 266 For example, the nmr spectrum of (266) showed, in addition to the signals due to the CH2OMEM, ethyl, and a l l y l groups, a 3-proton singlet at S 1.69, a 2-proton singlet at 5 2.85, a 1-proton doublet at 6 4.64 (J - 0.5 Hz) and a 1-proton doublet at 6 4.75 (J ~ 0.5 Hz). Furthermore, high resolution mass spectrometry showed that the molecular formula of (266) is C 1 6 H 2 8 0 3 . As a consequence of the clean and eff ic ient coupling between the vinylcopper(I) species (263) and 3-iodo-2-methylpropene, the reactions summarized in Table XI were carried out. It should be noted that the coupling reactions were quite eff ic ient even with substrate (223) (entries 1 and 2, Table XI) containing a f a i r l y bulky iso-propvl group. The reactions summarized in entries 1 and 2 afforded the corresponding alkenes, (264) and (265) in isolated yields of 77% and 70%, respec-t ive ly . Also of note is the eff ic ient introduction of a functionalized electrophile (2,3-dibromopropene) summarized by entries 2, 4 and 5. In each of the reactions (Table XI) the alkene (251) was isolated as the sole substitution product. The spectral data derived from these compounds were in f u l l accord with the assigned structures. The ^H nmr - 118 -Table XI: Preparation of vinylcopper(I) species and their reactions with electrophiles W / 1.n-BuLI. 249 / CuBr.Me2S Me2S.Cu _ R i W E' W 251 Entry 3 249 W E ' X b 251 Yie ld (%)c 223 i -Pr CH2OMEMc CH2=C(Me)CH2I 264 77 223 i -Pr CH2OMEMc CH2=C(Br)CH2Br 265 70 221 Et CH20MEMc CH2=C(Me)CH2I 266 69 221 Et CH20MEMc CH2=C(Br)CH2Br 267 78 227 Et CH=CH2 CH2=C(Br)CH2Br 268 74 Reaction conditions: A solution (THF, -78°C) of (249) was treated with n-BuLi (2.2 equiv), the reaction mixture was s t i rred at -78°C (10-15 min), CuBr.Me2S (1 equiv) was added, the mixture was s t i rred at -48°C (20-30 min), E'X was added, the mixture was s t i rred at -48°C (45-60 min) and then quenched (NH4C1-H20) or warmed to 25°C (30 min-7 h) and quenched (NH4CI -H2O) . These materials were passed through a column of act iv i ty I basic alumina immediately prior to use Yie ld of puri f ied , d i s t i l l e d product. MEM = CH20CH2CH20Me. - 119 -spectrum of compound (268) (entry 4) is depicted in F i g . 9. It is apparent from the eff ic ient formation of compounds (259) and (260) (entries 5 and 6, respectively, Table X) and compound (268) (entry 5, Table XI) , that the metal-coordinating OCH2OCH2CH2OMe function (see structure (269), in which M=Li or Cu-SMe2) is not necessary for effecting conversions of the type shown in equation 61 (in which W = CH20MEM). I, W E' W 269 Based on work'" ' 0 3 that had been carried out previously in our laboratory, we envisaged that, perhaps, suitable reagents derived from the v iny l iodides (249) could be conjugatively added to enones. We were thus pleased to find that after successive addition of magnesium bromide etherate (1.1 equiv), cuprous(I) bromide•dimethyl sulfide complex (0.23 eq), 2-cyclohexen-l-one (1.05 equiv) and boron tr i f luor ide etherate (1.1 e q u i v ) 8 6 to a THF:Et 2 0 (1:2). solution ( -78°C) of the vinyl l i thium reagent (262), followed by s t i r r i n g of the reaction mixture at -78°C for 3 h, the substituted cyclohexanone (270) was isolated in a y i e ld of 68% (equation 62). The spectral data derived from (270) was found to be in Fig. 9: The 400 MHz AH nmr spectrum of (268) - 121 -(62) f u l l accord with the assigned structure. For example, the i r spectrum showed an absorption at 1714 cm"1 attributable to the carbonyl stretch-ing frequency of a ketone function. The nmr spectrum of (270) showed, in addition to the signals due to the CH2OMEM, a l l y l , and ethyl groups, a 3-proton multiplet in the region 6 1.64-1.78, a 1-proton multiplet in the region S 2.07-2.17, a 2-proton multiplet in the region S 2.22-2.32, a 2-proton multiplet in the region 5 2.35-2.44 and a 1-proton multiplet in the region 5 3.04-3.12. Furthermore, high resolution mass spectrometry ver i f ied that the molecular formula of (270) is C 1 8 H 3 0 ° 4 -It should be noted that the y i e ld of (270) was lower (approximately 40%) when the reaction was performed on a large scale (up to 0.8 mmol), compared to the scale of the reaction discussed above (0.2 mmol). When the vinyl l i thium reagent derived from the transmetalation of (223) was treated with the reagents described above, the y i e ld of the corresponding conjugate addition product (271) was only 31% (equation 63). Presumably the steric bulk of the iso-propyl group is primarily responsible for the fact that the conjugate addition is very sluggish. In summary, i t i s worthwhile to note that in the tetrasubstituted alkenes prepared v ia the two methods discussed previously, two (trans) substituents on the double bond (R and W) are derived from readily - 122 -O OMEM ( 6 3 ) 2 7 1 synthesized a ,8-acetylenic esters, while the other two (trans) substituents (E and E') are introduced by alkylation reactions (Scheme 24). The demonstrated and potential f eas ib i l i ty of synthetically manipulating the ester function, along with the poss ib i l i ty of employing a wide variety of functionalized alkylating agents in addition to those l i s t ed in Tables X and IX, indicates that a versati le and effective synthesis of functionalized, stereochemically defined tetrasubstituted alkenes has been developed. 8 7 derived from second alkylation reaction derived from C02R' function R E from the parent acetylene R — = = —C0 2 R derived from transmetalation-alkylatlon reaction Scheme 24 - 123 -IV. Synthesis and chemistry of alkyl (E)-2-(tri-n-butylstannyl)-3-tri methylgermyl-2-alkenoates and alkyl (Z)-3-(tri-n-butylstannyl)-2-trimethylgermyl-2-alkenoates. A. Synthesis of the t i t l e compounds The Pd(0)-catalyzed addition of hexamethylditin to a a c e t y l e n i c esters has been shown to be a smooth and efficient process for the stereoselective formation of alkyl (Z)-2,3-bis(trimethylstannyl)-2-alkenoates. Recently, two reports in the l i t e r a t u r e 4 5 ' 4 6 demonstrated the f e a s i b i l i t y of adding 'mixed' bimetallic reagents to 1-alkynes. For example, i t was found that the Pd(0)-catalyzed addition of t r i a l k y l -s i l y l t r i m e t h y l t i n reagents to 1-alkynes afforded the corresponding adducts (272) in a regio- and stereoselective manner (equation 6 4 ) . 4 5 , 4 6 R'3SiSnMe3 Pd(PPh3)4 Me3Sn SiR' 3 - H R H (64) 81 272 The adducts (272) were isolated i n yields ranging from 65% (R - i-Pr, R' - __t-BuMe2) to 92% (R - THPOCH2CH2, R' - n-Bu). 4 6 b As a consequence, we decided to investigate the possibility of the Pd(0)-catalyzed addi-tion of trialkylstannyltrimethylgermanium compounds to a,B-acetylenic esters, and to determine the regiochemical outcome of such a reaction. In the f i r s t such study we decided to u t i l i z e trimethylgermyltri-methyltin, since this compound was conveniently prepared in 76% yield by - 124 -the addition of trimethylgermanium bromide to a solution of trimethyl-stannyllithium in THF at -20°C. As such, the following experiment was performed. To a solution of ethyl 2-butynoate (70) in THF was added trimethylgermyltrimethyltin (1 equiv) and (PPl^^Pd (0.02 equiv) and the mixture was s t i rred at 50-55°C for 30 h. Tic analysis ( s i l i c a gel, development with 9:1 petroleum ether-diethyl ether) of the reaction mixture indicated the presence of only one component (Rf = 0.40) and the absence of components corresponding to the starting materials. How-ever, glc analysis of an aliquot indicated the presence of 3 major components in a relative proportion of approximately 2:1:1. Removal of the solvent, followed by column chromatography of the brown o i l on s i l i c a gel afforded a clear colorless o i l . The ^H nmr spectrum of this o i l showed, amongst other signals, 3 dist inct signals at 5 2.07, 8 2.03 and 8 1.96, each of which corresponded to a v iny l methyl group. Integration of these singlets showed that these signals had relat ive areas of approximately 1:1.3:2.0, respectively. The compounds corre-sponding to these signals were subsequently identif ied as ethyl (Z)-2,3-bis(trimethylstannyl)-2-butenoate (124), ethyl (Z) -2 ,3 -b is ( tr i -methylgermyl)-3-trimethylstannyl-2-butenoate (273) and ethyl (Z) -3 - t r i -methylgermyl-2-trimethylstannyl-2-butenoate (274), respectively. Evidence for the structures of compounds (124), (273) and (274) was Me COjEt Me3Ge SnMe3 Me C02Et Me COzEt 124 273 274 - 125 -obtained as follows. When a mixture of these 3 inseparable compounds was heated at 110°-115°C for 10 h, t i c analysis ( s i l i c a gel , development with 9:1 petroleum ether-diethyl ether) indicated the presence of 3 major components (Rf — 0.62, 0.51, 0.40). Column chromatography of the crude o i l on s i l i c a gel readily afforded three o i l s , which were subse-quently ident i f ied as ethyl (E)-2,3-bis(trimethylstannyl)-2-butenoate (77), ethyl (Z)-2-trimethylgermyl-3-trimethylstannyl-2-butenoate (273) and ethyl (E)-3-trimethylgermyl-2-trimethylstannyl-2-butenoate (275). The former compound (77) was readily identif ied, since the corresponding Me3Sn C0 2Et Me3Sn GeMe 3 Me 3Ge C0 2Et H H H Me SnMe3 Me C0 2Et Me SnMe3 77 273 275 spectra were found to be identical with those of an authentic sample of ethyl (E)-2,3-bis(trimethylstannyl)-2-butenoate. As a consequence, of the i n i t i a l 3 inseparable compounds ((124), (273), (274)), the minor component was identif ied as ethyl (Z)-2,3-bis(trimethyl-stannyl)-2-butenoate (124). This assignment was made on the basis of the chemical shi f t of the v iny l methyl group (6 2.07), which was found to be Identical with that of the v iny l methyl group of an authentic sample of (124). The structures of compounds (273) and (275) were ver i f ied by analysis of the corresponding spectral data. For example, the i r spectra of (273) and (275) showed absorptions at 1709 cm"1 and 1704 cm" 1, respectively, attributable to the carbonyl stretching frequency of the a,/8-unsaturated ester functions. The nmr spectrum of (273) showed a 9-proton singlet at 6 0.23 (2J_Sri-H ** ^ 5 H z ^ ' a 9-proton singlet - 126 -at S 0.31 (-GeMe3). a 3-proton t r ip l e t at 6 1.27 (J - 7 Hz), a 3-proton singlet at 6 2.03 (3J.Sn-H ~ 4 8 H z)> a n d a 2-proton quartet at 6 4.18 (J - 7 Hz). On the other hand, the ^H nmr spectrum of (275) showed a 9-proton singlet at S 0.26 ( 2 Js n -H " 5 4 Hz), a 9-proton singlet at 5 0.27 (-GeMe 3). a 3-proton t r ip l e t at 6 1.27 ( 1 = 7 Hz), a 3-proton singlet at 6 2.00 (4J.Sn-H " 1 1 H z ) a n d a 2-proton quartet at 5 4.10 (J -7 Hz). Hence, on the basis of the J_sri-H v f l l u e s f ° r coupling between the t i n atom and the protons of the v iny l methyl group, the regiochemistry of compounds (273) and (275) was readily assigned. For instance, the 3Jsn-H v a l u e of 48 Hz (vinyl methyl of (273)) shows that the trimethyl-stannyl group must be B to the ester as depicted in structure (273). On the other hand, the 4J_s n-H v a l u e °^ ^ Hz ( v i - n y l methyl of (275)) shows that the trimethylstannyl group must be a to the ester function as depicted in structure (275) (or (274)). The stereochemical assignments related to compounds (273), (274) and (275) were made for the following reasons. The i n i t i a l Pd(0)-catalyzed addition of trimethylgermyltrimethyltin to ethyl 2-butynoate, under the mild reaction conditions described previously, can be assumed to lead to the formation of cis-adducts only ( i . e . (124), (273), (274)). During the subsequent thermolysis reaction, two of the adducts isomerized, (124) -+ (77) and (274) -» (275). That the latter isomerization process had occurred was shown by the fact that the signal due to the v iny l methyl group of (274) (5 1.96) disappeared during the thermolysis reaction. Moreover, the crude thermolysis product mixture showed a new singlet at 6 2.00 which was assigned to the v iny l methyl group of (275), the geometric isomer of (274). On the other hand, the signal at S 2.03, - 127 -corresponding to the v iny l methyl group of (273), was also present In the crude thermolysis reaction mixture. Hence, compound (273), ethyl (Z)-2-trimethylgermyl-3-trimethylstannyl-2-butenoate, had not undergone isomerization. Conclusive evidence for the stereochemical configuration of compounds such as (273) and (275) w i l l be presented later in this section of the thesis. I n i t i a l l y , the origin of compound (124) in the Pd(0)-catalyzed addition of trimethylgermyltrimethyltin to ethyl 2-butynoate (70) was puzzling. However, upon probing the l i t e r a t u r e , 4 6 ^ i t was found that tr imethyls i ly l tr imethylt in w i l l equilibrate with hexamethylditin and hexamethyldisilane in a reaction catalyzed by (PPl^^Pd under refluxing THF (equation 6 5 ) . However, i t has also been s h o w n , t h a t with t r i -Me 3SiSnMe 3 1 Me 3SiSiMe 3 + Me 3SnSnMe 3 (65) alkyls i lyltr ialkylstannanes in which the a lkyl groups attached to s i l i c o n or t i n are larger than methyl, the disproportionation reaction is inhibited. Presumably, trimethylgermyltrimethyltin undergoes a similar disproportionation reaction as shown in equation 6 5 . It has been shown that such a reaction does occur at room temperature in a polar s o l v e n t . ® 8 Indeed, when the Pd(O)-catalyzed addition of t r i -methylgermyltrimethyltin to ethyl 2-butynoate (70) was carried out in DMF at 5 0 - 5 5 ° C , the ^H nmr spectrum of the o i l obtained after workup showed the presence of compounds (77) (273) and (274) in a relative proportion of about 28:1:2, respectively. It was subsequently found that when the reaction was performed in the absence of solvent, the -^ H - 128 -nmr spectrum of the product mixture showed the presence of a 1:2.8:8.4 mixture of (77), (273) and (274). It may thus be noted that the rat io of (273) to (274) had increased from approximately 1:1 (THF) to 1:3 (neat). As a consequence, a l l subsequent reactions were performed in the absence of solvent. In order to avoid the presence of hexamethylditin in the Pd(0)-catalyzed addition reactions we decided to employ tr i -n-buty ls tannyl tr i -methylgermane. This reagent was prepared in 89% y ie ld by the reaction of t r i - n - b u t y l t i n hydride with IDA in THF at -20°C, followed by the addition of trimethylgermanium bromide (equation 66). Bu3SnH 1.LDA.THF Bu 3 SnGeMe 3 (66) 2.Me3GeBr 3 276 With a fac i le synthesis of (276) at hand, the following experiment was conducted in order to probe the u t i l i t y of the Pd(0)-catalyzed addition of (276) to a,^-acetylenic esters. Thus, when a mixture of ethyl 2-butynoate (70), (276) (1.03 equiv) and (PPt^^Pd (0.03 equiv) was s t i rred at 85°C for 24 h, t i c analysis ( s i l i c a gel, development with 95:5 petroleum ether-diethyl ether) indicated the presence of 3 compo-nents (Rf - 0.38, 0.53, 0.90). Column chromatography of the black o i l on s i l i c a gel afforded 3 o i l s , each of which was subjected to reduced pressure (vacuum pump, 0.1 Torr, 1 h) . Of the 3 substances, the least polar compound (Rf - 0.90) was found to correspond to (276) and was recovered in 22% y i e l d . Of the remaining two compounds, the major one (61% isolated yield) was subsequently identif ied as ethyl (E)-2- ( tr i -n-butylstannyl) -3-trimethylgermyl-2-butenoate (279) and the minor compound - 129 -(19% isolated yield) was identif ied as ethyl (Z) -3 - ( tr i -n -buty l -2 - tr i -methylgermyl-2-butenoate (280). The constitution of these latter compounds was readily determined by analysis of the corresponding spectral data. For instance, the i r spectra of (279) and (280) showed Me3Ge C0 2Et Bu3Sn GeMe3 H H Me SnBu3 Me COzEt 279 280 absorptions at 1704 and 1709 cm"l, respectively, attributable to the carbonyl stretching frequency of the a,^-unsaturated ester functions. The nmr spectrum of (279) showed a 9-proton singlet at S 0.24, a 9-proton t r i p l e t at 6 0.87 (J - 7 Hz), a 6-proton multiplet at 6 0.92-1.02, a 3-proton t r ip l e t at 6 1.27 (J - 7 Hz), a 6-proton multiplet at 6 1.20-1.39, a 6-proton multiplet at 6 1.40-1.58, a 3-proton singlet at S 1.95 (4J_Sn-H "* 1 0 H z ^ a n d a 2 _ P r o t o n quartet at S 4.08 (J = 7 Hz). On the other hand, the ^H nmr spectrum of (280) showed a 9-proton singlet at 5 0.30, a 9-proton t r ip l e t at S 0.90 (J - 7 Hz), a 6-proton multiplet at 5 0.92-1.00, a 3-proton t r ip l e t at S 1.29 (J = 7 Hz), a 6-proton multiplet at 6 1.23-1.40, a 6-proton multiplet at 6 1.40-1.57, a 3-proton singlet at 6 2.01 (3J_Sn-H ~ ^ ^z) and a 2-proton quartet at S 4.17. It should be noted that the magnitudes of the tin-proton coupling constants (J_Sn-H^ a r e * n a c c o r ( i with the regiochemical assign-ments in compounds (279) and (280). For instance, a value of 10 Hz (vinyl methyl group of (279)) is in accord with a 4J_Sn-H' w b - i c h c a n o n l y be attributed to compound (279) in which the t i n atom is a to the ester function. In addition to the above spectral data, high resolution mass - 130 -spectrometry ver i f i ed that the molecular formula of both compounds was c 2 1 H 4 4 ° 2 G e S n -It should be noted that in the addition reaction discussed above, 22% of the reagent (276) (n-Bu3SnGeMe3) was recovered after appropriate workup. Efforts were made to "force" the reaction to completion, but these were not successful. For example, longer reaction times resulted in a lower y ie ld of the addition products (279) and (280). Moreover, when an excess of (276) (- 5 equiv) was u t i l i z ed , the yields of the addition products remained unchanged, and over 4 equiv of (276) was returned. Increasing the amount of (PPl^^Pd to approximately 0.1 equiv actually led to a lower y ie ld of addition products. F ina l ly , changing the source of Pd(0) also had no effect on the reaction progress or on the regiochemical outcome of the reaction. Other Pd(0) sources that were used included bis(dibenzylideneacetone)palladium(0)/triphenyl-phosphine 6 6 and bis(triphenylphosphine)palladium(II)chloride/diisobutyl-aluminum h y d r i d e . 6 6 Since the Pd(0)-catalyzed addition of tri-n-butylstannyltrimethyl-germane (276) to ethyl 2-butynoate (70) proceeded in a reasonable y ie ld to afford the adducts (279) and (280), the generality of this reaction was investigated using a variety of a ,B-acetylenic esters (90). As such, the compounds of general structure (277) and (278) shown in Table XII were prepared in isolated yields of 48-61% and 14-19%, respectively. In each case (Table XII) the reactions were performed neat at tempera-tures of 8 5 C - 1 0 0 ° C for 5-24 h. The reactions were easi ly monitored by t i c analyses and the products were readily separated by column chroma-tography of the black o i l s on s i l i c a gel. A variety of functional - 131 -Table XII: Synthesis of a lkyl (E)-2-(tri-n-butylstannyl)-3-trimethyl-germyl-2-alkenoates (277) and alkyl (Z)-3- ( tr i -n-butyl -stannyl)-2-trimethylgermyl-2-alkenoates (278) MejGe^ C02R' BujSn^ GeMe 3 • COaR' •H • H R SnBu3 R COaR' 90 277 278 Entry 90 Reaction R' Condi-t ions 3 C C A ) 277 278 Yie ld (%)b 277,278 1 70 Me Et 85/24 279 280 61,19 2 115 i -Pr Me 86-90/24 281 282 48,15 3 98 C1CH2(CH2)4 Me 92-95/5 283 284 55,15 4 118 c tert-BuMe 2SiOCH 2(CH 2) 3 Me 95/14 285 286 56,14 5 119d THPOCH2CH2CH2 Me 95/5 287 287 55,15 6 121 d (3 -cyclohexenyl)methyl Me 100/16 289 290 53,16 A mixture of (90) (1 equiv), tri-n-butylstannyltrimethylgermane (1.0-1.5 equiv) and (PPl^^Pd (0.02-0.006 equiv) was s t irred under the conditions shown. Y ie ld of puri f ied , isolated product. This material was prepared by Dr. B.A. Keay according to the procedure of Chong. 2 These materials were prepared by Dr. J .M. Chong. 4 2 - 132 -groups present in the a,B-acetylenic ester ( 9 0 ) were tolerated: an alkyl chloride (entry 3), ether functions (entries 4,5) and a carbon-carbon double bond (entry 6). It should also be noted that the presence of the f a i r l y bulky iso-propyl group (entry 2) does not stop the reaction, although the y i e ld was s l ight ly lower than in the other reactions. In each case (Table XII) the ^ti nmr, i r and mass spectra are in complete agreement with the assigned structure. The stereochemical configurations of the addition adducts (277) and (278) were unequivocally corroborated by performing appropriate nmr decoupling and nOe difference experiments on the compounds (281) and (282) (entry 2, Table XII). For example, in the case of (281), i rradia -t ion of the doublet at S 2.08 (M^CH-) caused collapse of the multiplet at 6 2.33 (Me2CH-) to a singlet (with sate l l i te peaks due to Sn-H coupling) and showed that 4J_Sn-H ^ o r t n e lat ter signal is 9 Hz, a value typical of coupling between an a-Sn atom and a -y-H in an o,/9-unsaturated enhancement at 6 3.64 (-OMe) and S 1.12 (Me 2CH-), while irradiat ion at 6 3.64 (-OMe) caused signal enhancement at S 0.33 (-GeMe.3). On the other hand, in the case of (282), irradiat ion of the doublet at 6 1.00 (Me.2CH-) caused collapse of the septet at S 2.68 (Me2CH-) to a singlet (with sa te l l i t e peaks due to Sn-H coupling) and showed that 3J.Sn-H ^ o r the lat ter signal is 80 Hz, a value which corresponds to a coupling 281 282 ester. Furthermore, irradiat ion at 6 0.33 (-GeMe.3) caused signal - 133 -between a 8-Sn atom and a 7-H in an a,^-unsaturated ester. Furthermore, i rradiat ion at 6 0.32 (-GeMe.3) caused signal enhancement at 6 3.67 (-OMe), while irradiat ion at S 3.67 (-OMe) caused signal enhancement at 6 0.32 (-GeMe3) and 6 2.68 (Me2CH-). In addition, irradiat ion at S 2.68 (Me2CH-) caused signal enhancement at S 3.67 (-OMe) and 6 1.00 (Me 2CH-). The results of the decoupling and nOe difference experiments are consis-tent only with the structures depicted in formulas (281) and (282). Although the Pd(0)-catalyzed addition of (276) to other t r ip l e bonds was not extensively investigated i t was found that a single regio-and stereoisomer was obtained when the addition was carried out on a 1-alkyne and an N,N-dimethyl a,8-acetylenic alkynamide. For example, when a solution of N,N-dimethyl-2-butynamide (166) in benzene was treated with (276) (1 equiv). and (PPh^^Pd and the mixture was s t irred at 80°C for 31 h, t i c analysis indicated the presence of two components. After column chromatography of the crude o i l on s i l i c a gel two separate o i l s were obtained, one of which was found to correspond to (276) (72% recovery). The more polar compound was subsequently identif ied as ( £ ) - N , N- dime thy 1- 2-tri-n-butylstannyl- 3 -trimethylgermyl- 2-butenamide (291) (equation 67) and was isolated in 19% y ie ld . The spectral data of MejGe CONMe2  M . - ^ C O N M „ ) = ( I*" Me SnBuj 166 291 this compound was found to be in f u l l accord with the assigned structure (see Experimental section). The regiochemistry and the stereochemical - 134 -configuration was readily established from the •LH nmr spectrum and from nOe difference experiments. For example, the nmr spectrum of (291) showed a 3-proton singlet at 6* 1.92 with sa te l l i t e peaks due to Sn-H coupling. This coupling constant is 11 Hz which is in accord with a 4 J g n . j j and thus establishes that the t i n atom is o to the amide func-t ion. Furthermore, irradiat ion at 6 0.21 (-GeMe.3) caused signal enhancement at S 1.92 (vinyl methyl), 6 2.90 (-NMe) and 6 2.92 (-NMe), while irradiat ion at 5 1.92 (vinyl methyl) caused signal enhancement at 6 0.21 (-GeMe3) and 6 0.98 ( C H 3 ( C H 2 ) 2 C H 2 ) 3 S n - ) . Moreover, irradiat ion at 6 2.90 (-NMe) and 5 2.92 (-NMe) caused signal enhancement at 6 0.98 (CH 3 (CH 2 )2CH2)3Sn-) and S 0.21 (-GeMe.3). When a mixture of phenylacetylene, (279) (1.07 equiv) and (PPt^^Pd was s t i rred at 120°C for 24 h, t i c analysis of the mixture indicated the presence of two components. Glc analysis of an aliquot also indicated the presence of phenylacetylene. After column chromatography of the black o i l on s i l i c a gel two o i l s were obtained, one of which was found to correspond to (279) (67% recovery). The other compound was subsequently identif ied as (Z)-1-phenyl- l - tr i -n-butylstannyl-2-tri -methylgermylethene (292) (27% yield) (equation 68). The spectral data BuaSnGeMe, Pd(PPh3)4 Bu3Sn GeMe3 Ph (68) Ph H 2 9 2 of this la t ter material was found to be in f u l l accord with the assigned structure (see Experimental section). The regiochemistry and the - 135 -stereochemical configuration of (292) was unequivocally corroborated using a single piece of spectral data. The nmr spectrum of (292) showed, amongst other signals, a 1-proton singlet at 6 6.78 (vinyl proton) with sa te l l i t e peaks due to Sn-H coupling. The coupling constant associated with this coupling is 161 Hz which is in accord with a "^Isn-H (trans). The only structure in which such a coupling is possible is that shown by (292). It is not clear why the Pd(0)-catalyzed addition of t r i -n -buty l -stannyltrimethylgermane to a,B-acetylenic esters fa i l s to go to completion. However, i t is apparent that the reactions proceed to a much greater extent than those involving addition of n-Bu3SnGeMe3 to phenylacetylene or N,N-dimethyl-2-butynamide (166). Presumably, the ester function exerts a greater electronic effect on the t r ip le bond as compared to an amide function or phenyl group. It should be noted that the Pd(0)-catalyzed addition of hexabutylditin to ethyl 2-butynoate (70) also fa i l ed to go to completion (see Section II of the Discussion). This problem could perhaps be overcome by changing the a lkyl groups on t i n to a size intermediate in size between a methyl and a n-butyl group. For example, i f triethylstannyltrimethylgermane were to be used, the Pd(0)-catalyzed addition reaction should go to completion, since M i t c h e l l 4 3 0 had reported complete reaction in the Pd(0)-catalyzed addition of hexamethylditin to 1-alkynes. Moreover, disproportionation would presumably, not be a problem. 4 6** Presumably, a pathway which accounts for the Pd(0)-catalyzed addi-t ion of tri-n-butylstannyltrimethylgermane to a,B-acetylenic esters would be analogous to that depicted in Scheme 19, which i l lustrates the - 136 -pathway for the Pd(0)-catalyzed addition of hexamethylditin to a,/9-unsaturated esters. However, the i n i t i a l l y formed alkyl (Z) -2 - tr i -n-butylstannyl-3-trimethylgermyl-2-alkenoates (277A) would be expected to isomerize 3 9 under the reaction conditions to afford the geometric isomers (277) (equation 69). The mechanistic pathway accounting for Me3Ge SnBu3 Me3Ge C02R' 8J-10P°C ( 6 9 ) R C0 2R' R SnBu3 277A 277 this isomerization process (equation 69) is very l i k e l y analogous to that depicted for the alkyl 2,3-bis(trimethylstannyl)-2-alkenoates (e.g. see equation 23 and Scheme 20). Presumably, the isomerization of the other isomer (278) is a thermodynamically unfavourable process due to the strength of the germanium carbon bond. 9 Bu3Sn GeMe3 H R C02R" 278 However, the factors governing the regiochemical outcome of the Pd(0)-catalyzed addition of (276) to a , a c e t y l e n i c esters, in which the compounds (277) and (278) are formed in a ratio of approximately 3.3:1, respectively, are not clear. It does seem apparent, though, that steric factors are not very important since a similar rat io of 3:1 was obtained when the corresponding reaction was repeated with trimethylgermyltri-methyltin on the substrate ethyl 2-butynoate (70). It should also be - 137 -noted that even with a substrate containing the f a i r l y bulky iso-propyl group (entry 2, Table XII) , the ratio of (281):(282) was approximately 3:1, respectively. F ina l ly , the factors governing the regiochemical outcome of the Pd(0)-catalyzed addition of (276) to N..N-dimethyl-2-butynamide (166) and phenylacetylene are not clear. B. Spectral data of a lkyl (E)-2-(tri-n-butvlstannyl)-3-trimethylgermvl- 2-alkenoates and alkvl (Z)-3-(tri-n-butvlstannyl)-2-trimethylgermvl- 2-alkenoates Unlike the case of a lkyl 2,3-bis(trimethylstannyl)-2-alkenoates, nmr spectroscopy was not useful in determining the stereochemical configuration of the t i t l e compounds. In part icular , the chemical shifts of the 7 protons in the latter compounds did not vary appreciably within a given pair of isomers. This is in contrast to the a lkyl 2,3-bis(trimethylstannyl)-2-alkenoates (see Table III) . However, i t was found that nmr spectroscopy did provide a useful tool for corroborating the stereochemical configurations of (277) and (278), although the differences in the spectral data are not as pronounced as in the case of the a lkyl 2,3-bis(trimethylstannyl)-2-alkenoates (Tables IV and V) . Nevertheless, Table XIII contains a summary of some useful data observed in the nmr spectra of compounds (277) and (278). For instance, i f one considers the chemical shifts of the carbonyl carbon (6*CA) (Table XIII) the values range from 161.3-166.9 Table XI I I : Selected 1 3 C nmr data f o r compounds (277) and (278) A Me3Ge C0 2R' Bu 3Sn GeMe3 R D SnBu 3 RD CO 2 R. 277 2 7 8 A Chemical Shif t 8 J.Sn-Cb Entry R R' Conflgu- 277/ (6CA) («C B ) (*CC) ( « C D ) C (2 S n-C n > d (^Sn-C, ) ' ( 2 ISn-cJ f <3.lSn-C,>g ration 278 D 1 2 3 1 Me Et E 279 161. 3 146. 0 Z 280 155. 6 149. 8 2 i - P r Me E 281 166. 9 145. 0 Z 282 168. 0 146. 4 3 C1CH 2(CH 3)A Me E 283 166. 4 145. ,9 Z 284 160. 8 149. .2 4 tert-BuMe 2S10CH 2(CH 2) 3 Me E 285 166. 9 145. 5 z 286 161, ,2 148. .9 5 THPOCH2CH2CH2 Me E 287 166. .1 145. .6 Z 288 160, .6 149. .5 6 (3 -cyclohexenyl)methy1 Me E 289 166. .8 147 .0 Z 290 160 .0 149 .8 172. ,5 26. .6 50 326 20 60 171, 8 26. .7 48 320 19 60 173. .1 44. .6 52 325 20 62 172. 8 40, .2 44 317 18 67 172. .9 41 .9 47 328 20 61 172 .2 40 .9 46 320 18 62 173. .0 42 .0 47 331 19 J 172, .3 41 .1 44 320 18 64 172. .8 38 .8 47 327 20 61 172 .2 38 .0 46 320 20 64 172 .6 48 .4 44 327 19 61 172 .3 47 .9 44 320 18 65 h Chemical shift (6) was measured relative to the deuteriochloroform signal (5 7 7 . 0 ) ° 0 in ppm. A l l spectra were recorded on deuteriochloroform solutions. Coupling constants in Hz. In a l l cases apart from dsn-C^) t n e value quoted is obtained from the centres of the unresolved H^Sn and H^Sn sa te l l i t e s . {(Cp) refers to the chemical shift of the a l l y l i c carbon 7 to the ester function. J_Sn-Cn refers to 3 J.Sn-C n ^ o r t n e (£ ) isomers (277) and to 2J_Sn-C n ^ o r t b e —^^  isomers (278) e.g. Me 3Ge C 0 2 R ' Bu 3 Sn C D SnBu 3 3 i S n - C D = 3 J S n - C n (cis) D ^Sn-C '• coupling between the t in atom and the adjacent carbon of the n-butyl 1 group. In this case the value quoted is an average of the value for the H^Sn and H^Sn satel l i tes which were resolved separately. 2J_5n_C : coupling between the t in atom and the second nearest carbon of the 2 n-butyl group. 3 J g n _ C : coupling between the t in atom and the third nearest carbon of the 3 n-butyl group. This signal could not be measured. - 140 -ppm for the (E) isomers (compounds (277)) and from 155.6-168.0 ppm for the (Z) isomers (compounds (278)). As in the case of alkyl 2 ,3 -b i s ( tr i -methylstannyl) -2-alkenoates , the chemical shifts of the carbonyl carbons (5CA) of the (E) isomers are further downfield when compared to those of the corresponding (Z) isomers. For example, for the compounds appearing in entry 1 (compounds (279), (280)) the chemical shifts of the carbonyl carbons (6CA , Table XIII) are S 161.3 ((E) isomer) and 6 155.6 ((Z) isomer), respectively. This is consistent for a l l examples presented in Table XIII, apart from the compounds given in entry 2 (R - i.-Pr) . It is of interest to note that the chemical shifts of the v iny l i c carbons (5Cg) and (SCQ) are almost identical with the corresponding values for the alkyl 2,3-bis(trimethylstannyl)-2-alkenoates (Table IV). The chemical shift of (SCg) was found to decrease by approximately 3 ppm in going from the (Z) isomer (278) to the corresponding (E) isomer (277). A similar pattern is apparent in Table IV. Table XIII also contains a summary of tin-carbon coupling constants observed in the 1 3 C nmr spectra of compounds (277) and (278). These constants range from one bond coupling (^slsn-c) t o t n r e e bond coupling ( 3 Jg n _c) . It can be noted that for a l l examples (except those given in entry 2) the 22sn-C values (compounds (278)) are close to the 3J_sn-C values (compounds (277)). For instance, in the examples given by entry 1, the 3J_sn-Cn v a l u e i s 5 0 H z f o r t h e isomer (279) and the 2J.sn-CD value is 48 Hz for the (Z) isomer (280). This observation is similar to that made in the case of a lkyl 2,3-bis(trimethylstannyl)-2-alkenoates (Table V) , in which i t was noted that 2J.Sn-Cp w a s t n e s a m e a s ^ S n - C D (cis) for most of the cases l i s t ed in Table V. F i g . 10: The 75.6 MHz i J C nmr and APT spectra of (285) - 142 -Bu3Sn Bu !Me2SiO GeMe3 C02Me b c J mm a 1 1 1 1 m 1 1 1 1 1 1 1 40 20 I I I I I 1 I ' 1 1 1 1 1 1 0 PPM - r r p 200 ' ' I ' ' 180 140 120 T 1 80 i i I i i i i | i i i i | i 60 F i g . 11: The 75.6 MHz 1 3 C nmr and APT spectra of (286) - 143 -Me3Ge C 0 2 R ' B u 3 Sn C ° SnBu3 ^Sn-Cjj (cis) F ina l ly , the tin-carbon coupling constants between the t i n atom and the carbons of the n-butyl group (^slsn-C^ t o ^-Sn-C-j) deserve comment. As expected, the ^Sn-C^ values (coupling between the t i n atom and the adjacent carbon of the n-butyl group) are the largest, the average value being 320 Hz. However, the 3J_sn-c.j values (3-bond coupling) are the next largest, the average value being 60 Hz, followed by the 2J.Sn-C2 values (2-bond coupling), the average value being 20 Hz. These latter values are consistent with those reported in the l i t e r a t u r e . 8 9 The 1 3 C nmr spectra depicted in Figures 10 and 11 serve to i l l u s -trate the features discussed in this section of the thesis. C. Chemistry of ethyl (E)-2-(tri-n-butvlstannyl)-3-trimethvlgermvl-2- butenoate (279) Having established a route for the preparation of a lkyl (E) -2 - ( t r i -n-butylstannyl) -3-trimethylgermyl-2-alkenoates a program was in i t ia ted to determine the synthetic u t i l i t y of these substances. We had pre-viously shown (Section III.A of the discussion of this thesis) that the a-SnMe3 group of a lkyl 2,3-bis(trimethylstannyl)-2-alkenoates could be removed chemoselectively by transmetalation with methyllithium and that - 144 -the r e s u l t a n t n u c l e o p h i l i c intermediate reacted with a v a r i e t y of e l e c t r o p h i l e s to a f f o r d t r i s u b s t i t u t e d v inylstannanes (Table V I I I ) . As a consequence, our i n i t i a l ob jec t ive i n probing the u t i l i t y of compounds such as (279) i n s y n t h e s i s , was to determine the f e a s i b i l i t y of the corresponding t r a n s m e t a l a t i o n - a l k y l a t i o n r e a c t i o n . As expected, i t was found that the t r a n s m e t a l a t i o n - a l k y l a t i o n r e a c t i o n of compound (279) was a f a c i l e and e f f i c i e n t p r o c e s s . For example, a s o l u t i o n of (279) i n THF was t rea ted with 1.2 equiv of n - b u t y l l i t h i u m ( in hexane) at -98°C fo r 20 min. 3-Iodopropene was added to the pale yel low s o l u t i o n and the mixture was s t i r r e d at -98°C f o r 40 min. A f t e r the mixture had been quenched with saturated aqueous ammonium c h l o r i d e , g l c and t i c analyses of the s o l u t i o n showed the presence o f two components. The l e s s po la r compound (Rf — 0.90) ( s i l i c a g e l , development with 95:5 petroleum e t h e r - d i e t h y l ether) was found to correspond to t e t r a b u t y l t i n , whi le the more po la r compound (Rf - 0.37) was subsequently i d e n t i f i e d as e t h y l ( Z ) - 2 - ( 2 - p r o p e n y l ) - 3 - t r i m e t h y l -germyl-2-butenoate (294) (equation 70). A f t e r appropr iate workup, t h i s m a t e r i a l was i s o l a t e d i n 80% y i e l d . The s p e c t r a l data obtained from (294) was found to be i n f u l l accord with the assigned s t r u c t u r e . For example, the i r spectrum of (294) showed an absorpt ion at 1713 cm" 1 a t t r i b u t a b l e to the carbonyl s t r e t c h i n g frequency of an a .^ -unsatura ted Me3Ge C0 2Et * 1.n-BuLI,THF,-98eC Me3Ge C0 2Et , -98°C (70) Me Me 294 - 145 -ester function. The nmr spectrum of (294) showed a 9-proton singlet at 5 0.27, a 3-proton t r ip l e t at 6* 1.27 (J - 7 Hz), a 3-proton singlet at 6 1.90, a 2-proton doublet at 6 3.16 (J = 6 Hz), a 2-proton quartet at 6* 4.15 (J - 7 Hz), a 1-proton dd at 8 4.96 (J - 10, 2 Hz), a 1-proton dd at 8 4.98 (J - 17, 2 Hz) and a 1-proton ddt at 8 5.78 (J - 17, 10, 6 Hz). Furthermore, high resolution mass spectrometry ver i f i ed that the molecular formula of (294) is 0-12^2^2^ • The results of reactions involving the use of (279) and some other alkylating agents are summarized in Table XIV. These reactions pro-ceeded in yields ranging from 42% to 77%, although in these cases the yields have not been optimized. When reactive alkylating agents were employed (entries 1-3), the yields of substitution product were good. However, when a less reactive alkylating agent, for example, 1-chlo-ro-3-iodopropane (entry 4) was employed the y ie ld was only 42%. It should be noted that, in each case (Table XIV), the by-product of the transmetalation reaction, tetrabutylt in, was readily removed by column chromatography of the crude o i l on s i l i c a gel, affording the ester (293) as the sole substitution product. A l l compounds shown in Table XIV exhibited ^H nmr, i r and mass spectra in f u l l accord with the assigned structures. As expected, based on the results of the transmetalation-alkylation reactions of a lkyl 2,3-bis(trimethylstannyl)-2-alkenoates, the corre-sponding reactions with (279) proceeded to afford adducts (293), in which the trimethylgermyl group and the ester function are c is-related. Presumably, transmetalation of (279) leads to the formation of an allenoate a n i o n 3 9 (298), which alkylates from the side opposite the - 146 -Table XIV: Transmetalat ion of methyl ( E ) - 2 - ( t r i - n - b u t y l s t a n n y l ) - 3 - t r i -methylgermyl-2-butenoate (279) and reac t ions of the r e s u l t a n t intermediate with e l e c t r o p h i l e s Me3Ge C0 2Et Me3Ge C0 2Et \ / 1.n-BuLI,THF,-98"C \ / / \ 2.EX,-98°C / V Me SnBu3 Me E 279 293 E n t r y 3 EX b 293 Y i e l d (%)c 1 CH2=CHCH2I 294 80 2 Mel 295 77 3 Me2C=CHCH2Br 296 74 4 d C1CH 2 CH 2 CH 2 I 297 42 React ion c o n d i t i o n s : A s o l u t i o n (THF, - 98 °C ) of (279) was t rea ted with n-BuLi (1.1-1 .2 equ iv ) , the mixture was s t i r r e d at -98°C (15-20 min) , EX was added, the mixture was s t i r r e d at -98°C f o r up to 45 min and then quenched (NH4C1-H 20). These mater ia ls were passed through a column of a c t i v i t y I b a s i c alumina immediately p r i o r to use , with the except ion of l -bromo-3-methyl -2 -butene (entry 3), which was d i s t i l l e d immediately p r i o r to use . Y i e l d o f p u r i f i e d , d i s t i l l e d product . In t h i s r e a c t i o n , the r e a c t i o n mixture was warmed to - 7 8 ° C . - 147 -bulky trimethylgermyl group, thus affording a single stereoisomer (293) (equation 71). Me3Ge C0 2 Et Me3Ge OEt Me3Ge C0 2Et H )—< •«—H ,71) Me SnBu3 Me OLI Me E 279 298 293 The stereochemical configuration assigned to the substitution products (293) was unequivocally established by performing a nOe difference experiment on a representative example. Thus, in the nmr spectrum of (294), irradiat ion of the singlet at 5 1.90 (vinyl methyl) caused signal enhancement at 5 5.78 (CH2=CHCH2-), 6 5.16 (CH2=CHCH2-) and 5 0.27 (-GeMe3). Me3 294 Interestingly, when ethyl (Z)-3-(tri-n-butylstannyl)-2-trimethyl-germyl-2-butenoate (280) was treated successively with n-butyllithium and iodomethane, a result quite different from that derived from a similar procedure with compound (279) was observed. Thus, a solution of (280) in THF was treated with 1.2 equiv of n-butyllithium (in hexane) at -98°C for 15 min. Iodomethane was added and the solution was s t i rred at -98°C for 45 min and at -78°C for 45 min. After appropriate workup, a single product was isolated in 75% y ie ld . This material was subse-quently identi f ied as ethyl 2-methyl-3-(tri-n-butylstannyl)-2-trimethyl-germyl-3-butenoate (299) (equation 72). The spectral data derived from (299) were found to be in f u l l accord with the assigned structure. For - 148 -Bu3Sn GeMe3 SnBu 3 H 1. n-BuLI,THF,-98°C 2. Mel,-98° — -78°C (72) C02CHcHDCH'3 Me C0 2Et 3.NH4CI 280 Me3Ge Me 299 example, the i r spectrum showed an absorption at 1681 cm attributable to the carbonyl stretching frequency of the ester function. The -"-H nmr spectrum of (299), in addition to the signals due to the t r i -n -buty l -stannyl group, showed a 9-proton singlet at S 0.20, a 3-proton singlet at S 1.41, a 1-proton dq at 6 4.06 (J - 11, 7 Hz), a 1-proton dq at 6 4.17 (J - 11, 7 Hz), a 1-proton doublet at 6 5.27 (J - 1.5 Hz, 3 J_s n -H = 68 Hz) and a 1-proton singlet at 5 5.66 (J •= 1.5 Hz, 3J_s n-H = 1 4 6 H z ^'• Furthermore, high resolution mass spectrometry showed that the molecular formula of (299) is C 2 2 H 4 6 ° 2 G ^ S n -Presumably, the s ter ica l ly hindered nature of the tri-n-butylstannyl group of (280) hinders the transmetalation of this moiety. On the other hand, i t is the strength of the germanium-carbon bond^ which accounts for the lack of react iv i ty of the trimethylgermyl group of (280) towards the transmetalation process. As a consequence, treatment of (280) with n-butyllithium led to the deprotonation of (280) affording an enolate anion. This species upon treatment with iodomethane afforded (299) as the sole substitution product. With a fac i le synthesis of trisubstituted vinylgermanes of general structure (293) at hand, our next objective was to investigate the u t i l i t y of these compounds for synthesis. In part icular , we envisaged conversion of the ester moiety of (293) into the corresponding alcohol (300). Successive manipulation of this latter material, by a sequence - 149 -of steps s i m i l a r to that d iscussed i n the previous s e c t i o n of t h i s t h e s i s , could e i t h e r a f f o r d the ether (301) or the a l l y l i c h a l i d e (302) (X = halogen) . I t may be noted that (302) i s p o t e n t i a l l y s y n t h e t i c a l l y equiva lent to the d , a synthon represented by s t ruc ture (303) (Scheme 25). Me3Ge C0 2Et Me3Ge y— OH I j— X r \ r=\ r \ Me E Me E Me E 293 300 302 H 'A Me E Me E 301 303 Scheme 25 As expected, the reduct ion of the es ter func t ion of compounds (293) to the a l l y l i c a lcohols (300) was a f a c i l e process . For example, a s o l u t i o n o f (294) i n ether was t rea ted with DIBAL at - 7 8 ° C for 1 h and at 0°C for 2 h . A f t e r appropriate workup, a s i n g l e compound was i s o l a t e d i n 100% y i e l d . Th i s substance was subsequently i d e n t i f i e d as ( Z ) - 2 - ( 2 - p r o p e n y l ) - 3 - t r i m e t h y l g e r m y l - 2 - b u t e n - l - o l (304). The s p e c t r a l data der ived from t h i s compound was found to be i n f u l l accord with the M e 3 ° e \ / — °^ / \ _ / Me ' 304 - 150 -assigned structure. For example, the i r spectrum showed a broad absorption at 3336 cm"1 attributable to the O-H stretching frequency of an alcohol function. The ^H nmr spectrum of (304) showed, in addition to the signals due to an a l l y l group, a 9-proton singlet at S 0.30, a broad 1-proton singlet in the region 6 1.51-1.60, a 3-proton singlet at S 1.79 and a 2-proton singlet at 6 4.09. Furthermore, high resolution mass spectrometry showed that the molecular formula of (304) is C 1 0 H 2 0 O G e . The subsequent conversion of (304) into the corresponding ether (305) was readily accomplished. Thus, when a solution of (304) in CH2CI2 was treated with methoxymethyl chloride and N,N-diisopropylethyl-amine and the mixture was s t irred at room temperature for 23 h, the ether (305) was isolated in 66% yie ld after appropriate workup. The spectral data derived from this compound were found to be in f u l l accord with the assigned structure. For example, the ^H nmr spectrum of (305) c learly showed the presence of a methoxymethyl ether moiety which gave r ise to a 3-proton singlet at S 3.40, a 2-proton singlet at S 4.01 and a 2-proton singlet at 6 4.63. In analogy to vinylstannanes, vinylgermanes also undergo faci le metal-iodine exchange.9^ Thus, when a solution of (305) in CH2CI2 was treated with iodine, and the mixture was s t i rred at room temperature u n t i l a pale purple color persisted, the iodide (306) was isolated in 305 - 151 -83% y i e ld after appropriate workup. Similarly, treatment of a solution of the alcohol (304) in CH2Cl2 with iodine, afforded the iodide (307) in The stereochemical configuration of (306) and (307) was unequivo-ca l ly established by performing a nOe difference experiment on compound (306) . For example, irradiat ion of the singlet at 6 2.57 (vinyl methyl) caused signal enhancement at 6 5.05 (vinyl proton) and 5 5.75 (vinyl proton). We were pleased to find that the alcohol (307) could be converted smoothly into.the corresponding a l l y l i c bromide (308) . Thus, a solution of the alcohol (307) in CH2CI2 was added dropwise to a solution of t r i -phenylphosphine and bromine 9 1 at -20°C. After the reaction mixture had been warmed to room temperature, t i c analysis of the solution showed the presence of only one component (Rf = 0.70) ( s i l i c a gel, development with 95:5 petroleum ether-diethyl ether). After appropriate workup, the bromide (308) was isolated in 92% y ie ld (equation 73). The spectral data derived from (308) were in f u l l accord with the assigned structure. 72% y ie ld . The spectral data derived from (306) and (307) were found to be in f u l l accord with the assigned structure. 306 307 (73) 307 308 - 152 -For example, the -^H nmr spectrum of (308) showed, in addition to the signals due to an a l l y l group, a 3-proton singlet at S 2 . 5 8 and a 2-proton singlet at S 4 . 2 0 . Furthermore, high resolution mass spectrometry showed that the molecular formula of (308) is C-JU^QBTI. The u t i l i t y of compound (308) as an intermediate for the formation of b i cyc l i c dienes w i l l be discussed in the next section of this thesis. V . Synthesis of b icyc l i c and t r i c y c l i c ring systems As discussed in section III.A of this thesis, the preparation of cyc l ic 6-trimethylstannyl a,^-unsaturated esters from the corresponding a lkyl w-halo-2 ,3-bis(trimethylstannyl)-2-alkenoates was shown to be a fac i le process. The former materials had been u t i l i z e d previously for the development of a new annulation sequence. 6 3 In part icular, i t had been shown that the enolate anion derived from cycl ic 8-trimethylstannyl a,y9-unsaturated esters (203) (in which n = 1 or 2) could be trapped with alkylating agents to afford compounds (309) (equation 7 4 ) . 6 3 Thus, i t SnMe3 C02Me LDA-THF-HMPA I**s*V>C02Me j (74) E X was envisaged that alkylation of compounds (203) with an appropriately functionalized alkylating agent such as (308) (potentially synthetically equivalent to the d,a synthon (310)), could lead to the formation of compounds of general structure (311). Conceivably, these latter - 153 -compounds, on the basis of S t i l l e ' s work, 2 could undergo intramolecular Pd(0)-catalyzed cross-coupling of the vinylstannane and v iny l iodide functions to afford b icyc l i c dienes of general structure (312) (Scheme 26). 310 312 Me Scheme 26 We were pleased to find that the alkylation of compounds (203) with the alkylating agent (308) was a fac i le process. For example, a solution of methyl 2-trimethylstannyl-l-cyclohexenecarboxylate (206) in THF was treated with a solution of lithium diisopropylamide (THF) at -20"C for 30 min. The yellow solution was successively treated with HMPA (3 equiv) (15 min) and the alkylating agent: (308) ( - 2 0 ° C , 30 min) and then was quenched with saturated aqueous ammonium chloride. Tic analysis of the reaction mixture showed the presence of one major component (Rf - 0.42) ( s i l i c a gel, development with 95:5 petroleum ether-diethyl ether), which was subsequently ident i f i ed as the ester (313). After appropriate workup, the ester (313) was isolated in 66% y i e l d (equation 75). The spectral data derived from (313) were found to - 154 -be In f u l l accord with the assigned structure. For example, the i r spectrum showed an absorption at 1733 cm"1 attributable to the carbonyl stretching frequency of an ester function and an absorption at 769 cm"1 attributable to the tin-methyl rocking frequency of a trimethylstannyl group. The nmr spectrum of (313) showed, apart from the signals due to the a l l y l group, a 9-proton singlet at 6 0.15 ( 2J_s n-H "° ^ 4 Hz), a 3-proton multiplet in the region S 1.60-1.79, a 3-proton multiplet in the region 6 2.01-2.16, a 3-proton singlet at 5 2.55, a 1-proton doublet at S 2.56 ( J = 14 Hz), a 1-proton doublet at S 3.00 ( J = 14 Hz), a 3-proton singlet at S 3.69 and a 1-proton t r ip l e t at S 5.99 (J = 3.5 Hz, o J_Sn-H — 74 Hz). Furthermore, high resolution mass spectrometry showed that the molecular formula of (313) is C^gH2g02lSn. The Pd(0)-catalyzed cross-coupling reaction of the vinylstannane-v iny l iodide (313) was found to be a smooth and eff ic ient process. Thus, a solution of triphenylphosphine, triethylamine and palladium(II) acetate in CH3CN55 was added to a solution of (313) in CH3CN and the mixture was s t i rred at 80°C for 4 h, t i c analysis of an aliquot indicated the absence of starting material and the presence of a new component (Rf — 0.28) ( s i l i c a gel, development with 95:5 petroleum ether-diethyl ether). After appropriate workup, the triene (314) was isolated in 81% y ie ld . The spectral data derived from (314) were found - 155 -to be in f u l l accord with the assigned structure. For example the i r spectrum showed an absorption at 1728 cm"! attributable to the carbonyl stretching frequency of an ester function. The nmr spectrum of (314) showed, apart from the signals due to an a l l y l group, a 2-proton multiplet in the region 6 1.43-1.52, a 1-proton multiplet in the region S 1.71-1.79, a 3-proton singlet at S 1.73, a 1-proton multiplet in the region S 2.05-2.16, a 1-proton multiplet in the region 5 2.20-2.31, a 1-proton multiplet in the region 6* 2.33-2.42, a 1-proton doublet at 6 2.39 (J = 16 Hz), a 1-proton doublet at S 2.68 (J = 16 Hz), a 3-proton singlet at S 3.65, and a 1-proton t r ip l e t at 6 5.47 (J = 4 Hz). In addition, high resolution mass spectrometry showed that the molecular formula of (314) is C15H20O2. It should be noted that when the Pd(0)-catalyzed cross-coupling reaction described above was performed in THF, the reaction was not clean since t i c analysis of the reaction mixture indicated the presence of other unidentified components. As a consequence, the isolated y ie ld of (314) was lower (38%), compared to when the reaction was performed in CH3CN (81%). On the other hand, when the reaction was performed in DMF the isolated y i e ld of (314) was 72%. Although the effect of using alternative sources of Pd(0) was not extensively investigated, i t was found that when (PPV^^Pd was employed, t i c analysis of the reaction Me02C Me 3 1 4 - 156 -mixture indicated the presence of unidentified components. By u t i l i z i n g a sequence of steps analogous to those described above the triene (316) was prepared- Thus, when a THF solution of the enolate anion derived from treatment of methyl 2-trimethylstannyl-l-cyclo-heptenecarboxylate (207) with LDA, was successively treated with HMPA and the alkylating agent (308) at -20°C for 1 h, the corresponding ester (315) was isolated in 51% y ie ld after appropriate workup. Treatment of an CH3CN solution of (315) with a solution of triphenylphosphine, triethylamine and palladium(II) acetate in CH3CN for 2.5 h at 70-75°C, afforded the triene (316) as the only product in 85% y ie ld after appropriate workup (equation 1€) . The spectral data derived from compounds (315) and (316) were found to be in f u l l accord with the as s i gne d s true ture s. (76) Similarly, when a THF solution of the enolate anion derived from treatment of methyl 2-trimethylstannyl-l-cyclopentenecarboxylate (205) with LDA, was successively treated with HMPA and the alkylating agent (308) at -20°C for 1 h, the corresponding ester (317) was isolated in 66% y ie ld after appropriate workup. The spectral data derived from (317) was found to be in f u l l accord with the assigned structure. For example, the ^H nmr spectrum of (317) showed, apart from the signals due to the v iny l group, a 9-proton singlet at S 0.17 (^isn-H *° -*4 Hz), a 1-proton ddd at S 2.0 (J = 13, 8, 4 Hz), a 1-proton ddd at 6 2.29 (J = - 157 -13, 8, 6.5 Hz), a 2-proton multiplet in the region S 2.44-2.61, a 1-proton doublet at S 2.50 (J = 14 Hz), a 3-proton singlet at S 2.55, a 1-proton dd at 6 2.67 (J - 15.5, 6.5 Hz), a 1-proton dd at J 3.02 . (J -15.5, 6.5 Hz), a 1-proton doublet at 6 3.04 (J = 14 Hz), a 3-proton singlet at S 3.68 and a 1-proton t r ip l e t at 6 5.98 (J - 2.5 Hz, 3 J g n . H -38 Hz). In addition, high resolution mass spectrometry ver i f i ed that the molecular formula of (317) is C^yH2702lSn. 317 When an CH3CN solution of (317) was treated with a solution of triphenylphosphine, triethylamine and palladium(II) acetate in CH3CN for 30 h at 65 -70°C, t i c analysis of an aliquot showed the presence of two components. The less polar component was found to correspond to a mixture of unidentified compounds, while the more polar component was subsequently identif ied as the triene (318). After appropriate workup, this material was isolated in 55% y ie ld . Although the y i e ld of (318) is lower, compared to the previous two examples (314) and (316), i t should be noted that there is considerable strain associated with the conjugated diene system in the bicyclo[3.3.0]nonadiene (318). This inherent s train could account for the lower y ie ld of the ring closure. The spectral data derived from (318) were in f u l l accord with the assigned structure. A further poss ib i l i ty that we envisaged was to transform the cyc l ic - 158 -318 M e B-trimethylstannyl a,^-unsaturated esters (203) into alkylating agents of general structure (319), which are potential ly synthetically equivalent to the d,a synthons (320). Conceivably, alkylation of compounds (203) with compounds (319) would afford the corresponding products (321), which upon subjection to a Pd(0) catalyst, would be transformed into t r i c y c l i c dienes of general structure (322) (Scheme 27). Scheme 27 The preparation of compounds of general structure (319) was found to be an ef f ic ient process. For example, when a solution of methyl 2 - t r i -methylstannyl -1-cyclopentenecarboxylate (205) in ether was treated with DIBAL at -78°C for 1 h and 0°C for 2 h, the corresponding alcohol (323) - 159 -was isolated in 100% yie ld after appropriate workup. The i r spectrum of (323) showed a broad absorption at 3343 cm"! attributable to the 0-H stretching frequency of an alcohol function. Treatment of a solution of the alcohol (323) with iodine at room temperature, afforded the iodide (324) in an isolated y i e ld of 88%. When a solution of the iodide (324) in CH2CI2 was added to a solution of triphenylphosphine and bromine at -20°C, the corresponding bromide (325) was isolated in 80% y ie ld after appropriate workup (equation 77). High resolution mass spectrometry of derived from compounds (323), (324) and (325) are in f u l l accord with the assigned structures. The alkylation of compounds (203) with the alkylating agent (325) was found to be a fac i le process. For example, a solution of methyl 2-trimethylstannyl-1-cyclopentenecarboxylate (205) in THF was treated with a solution of lithium diisopropylamide at -48°C for 30 min. The yellow solution was successively treated with HMPA (3 equiv, 10 min), and the alkylating agent (325) ( -48°C, 30 min) and then was quenched with saturated aqueous ammonium chloride. Tic analysis of the reaction mixture showed the presence of one major component (Rf = 0.34) ( s i l i c a gel , development with 95:5 petroleum ether-diethyl ether) and a minor less polar component (Rf = 0.68), which was not identif ied. After appropriate workup, the major component was isolated in 64% y ie ld and 323 324 325 (325) showed that the molecular formula was CgH3BrI. The spectral data - 160 -was subsequently i d e n t i f i e d as the ester (326). The s p e c t r a l data der ived from (326) were found to be i n f u l l accord with the assigned s t r u c t u r e . For example, the i r spectrum showed an absorpt ion at 1734 c m " 1 a t t r i b u t a b l e to the carbonyl s t r e t c h i n g frequency of an es te r SnMe3 326 f u n c t i o n and an absorpt ion at 771 cm" 1 a t t r i b u t a b l e to the t in -methy l r o c k i n g frequency of a t r imethy ls tanny l group. The nmr spectrum of (326) showed a 9-proton s i n g l e t at 5 0.19 ( 2 J _ s n - H = ^4 Hz) , a l^proton ddd at 8 1.79 (J - 13, 7, 6 .5 .Hz ) , a 2-proton qu in te t at 6 1.89 (J - 7.5 Hz ) , a 2-proton m u l t i p l e t i n the reg ion 8 2 .08-2.24, a 1-proton doublet at 6 2.27 (J = 14 Hz) , a 1-proton ddd at 6 2.37 (J = 13, 7, 6.5 Hz) , a 2 -proton ddd at 6 2.51 (J - 7, 6 .5 , 2 Hz) , a 2-proton m u l t i p l e t i n the reg ion 8 2 .60-2 .70 , a 1-proton doublet at 6 2.90 (J = 14 Hz) , a 3-proton s i n g l e t at 6 3.67 and a 1-proton t r i p l e t at 8 5.99 (J = 2 Hz, ^ i s n - H = 37 Hz) . Furthermore, h igh r e s o l u t i o n mass spectrometry v e r i f i e d that the molecular formula o f (326) i s C^gH2502lSn. When an CH3CN s o l u t i o n of (326) was t rea ted with a s o l u t i o n of t r i -phenylphosphine, t r ie thy lamine and pal ladium(I I ) acetate i n CH3CN and the mixture was s t i r r e d at 80 CC f o r 24 h , t i c a n a l y s i s i n d i c a t e d the absence o f s t a r t i n g mate r ia l and the presence of one major component (Rf - 0.20) ( s i l i c a g e l , development with 95:5 petroleum e t h e r - d i e t h y l e t h e r ) . A f t e r appropr ia te workup, the diene (327) was i s o l a t e d i n 68% - 161 -y i e l d . The spectral data derived from (327) were in f u l l accord with the assigned structure. For example, the nmr spectrum of (327) showed a 1-proton ddd at 5 1.77 (J - 12, 9, 8 Hz), a 4-proton multiplet in the region 6 1.91-2.08, a 3-proton multiplet in the region 6 2.12-2.33, a 1-proton dd at 6* 2.41 (J - 12, 6 Hz), a 1-proton multiplet in the region S 2.40-2.50, a 1-proton doublet at 6 2.98 (J - 16 Hz), a 1-proton multiplet in the region 6 3.00-3.11, a 3-proton singlet at 6 3.31 and a 1-proton broad singlet at 6 5.33. Furthermore, high resolution mass spectrometry ver i f ied that the molecular formula of (327) is C 1 3 H 1 6 0 2 . It should be pointed out that the formation of the diene (327) is noteworthy considering the strain inherent in the molecule. By u t i l i z i n g a sequence of steps analogous to those described above the diene (329) was prepared. Thus, when a THF solution of the enolate anion derived from the treatment of methyl 2-trimethylstannyl-1-cyclo-hexenecarboxylate (206) with LDA, was successively treated with HMPA and the alkylating agent (325) at -20°C for 30 min, the corresponding ester (328) was isolated in 66% y ie ld after appropriate workup. Treatment of an CH3CN solution of (328) with a solution of triphenylphosphine, t r i -ethylamine and palladium(II) acetate in CH3CN for 21 h at 80°C, afforded the diene (329) in 70% y ie ld after appropriate workup (equation 78). The spectral data derived from compounds (328) and (329) were found to C02Me - 162 -Me0 2C C0 2 Me Pd(0) CHjCN (78) SnMe 3 328 329 be in f u l l accord with the assigned structures. Similarly , when a THF solution of the enolate anion derived from the treatment of methyl 2-trimethylstannyl-l-cycloheptenecarboxylate (207) with LDA, was successively treated with HMPA and the alkylating agent (325) at -48°C for 45 min, the corresponding ester (330) was isolated in 56% y ie ld after appropriate workup. Treatment of an CH3CN solution of (330) with a solution of triphenylphosphine, triethylamine and pal la-dium(II) acetate in CH3CN for 4 h at 85°C afforded the diene (331) in 80% y ie ld after appropriate workup (equation 79). The spectral data derived from compounds (330) and (331) were found to be in f u l l accord with the assigned structures. For example, the ^H nmr spectrum of (330) showed a 9-proton singlet at S 0.15 (^J.Sn-H ~ 4^ Hz), a 1-proton multiplet in the region 6 1.22-1.35, a 2-proton multiplet in the region S 1.48-1.57, a 2-proton multiplet in the region 6* 1.64-1.72, a 2-proton quintet at 6 1.89 (J = 7.5 Hz), a 5-proton multiplet in the region 6* 2.02-2.23, a 1-proton doublet at 6 2.43 (J - 14 Hz), a 2-proton (79) 330 331 - 163 -multiplet in the region 6 2.59-2.68, a 1-proton doublet at 5 2.81 (J = 14 Hz), a 3-proton singlet at 6 3.68 and a 1-proton t r ip l e t at 6 6.00 (J - 3.5 Hz, isn-H = 7 4 Hz). In addition, high resolution mass spectro-metry ver i f i ed that the molecular formula of (330) is Cigh^o^ISn. A possible pathway for the intramolecular Pd(O)-catalyzed cross-coupling reaction of vinylstannanes-vinyl iodides (or bromides) is represented by the catalyt ic cycle shown in Scheme 28. The f i r s t step tc> XSnMe3 Scheme 28 can be envisaged to be oxidative addition of the carbon-halide bond to the PdL 2 catalyst to afford an intermediate represented by [A]. This species could then undergo trans/cis isomerization to afford an inter-mediate depicted by [B]. Transmetalation of the vinylstannane by pal la-dium would result in the formation of trimethylstannyl halide and the - 164 -palladium complex [C]. This l a t t e r species could undergo reductive e l i m i n a t i o n to a f f o r d the diene product [D] and the palladium c a t a l y s t PdL 2. The palladium c a t a l y s t PdL 2 could then undergo another c a t a l y t i c c ycle. In conclusion, i t i s c l e a r that many modifications and extensions to the intramolecular Pd(0)-catalyzed cross-coupling reactions described above can be envisaged. However, i t i s already apparent that a v a r i e t y of b i c y c l i c ^ 2 t r i e n e and t r i c y c l i c diene systems have been prepared, thus i l l u s t r a t i n g the p o s s i b i l i t y of applying t h i s methodology to nat u r a l product synthesis. In p a r t i c u l a r , i t should be noted that the syntheses of f u n c t i o n a l i z e d bicyclo[5.3.0]decadienes (e.g. (316)) and triquinanes (e.g. (327)) are examples of r i n g systems found i n many natural products. VI. Miscellaneous In the e a r l y part of the discussion (section II.A) of t h i s t h e s i s , the p o s s i b i l i t y of an intramolecular Pd(0)-catalyzed cross-coupling r e a c t i o n between the vinylstannane and v i n y l bromide functions of com-pound (134) to a f f o r d compound (143) was discussed (equation 80). I t was found that when a s o l u t i o n of (134) i n THF was treated with ( P P l ^ ^ P d Br COjMe Pd(PPh 3 ) 4 SnMe3 T H F SnMe3 (80) 134 SnMe3 C02Me 143 - 165 -for 24 h at 50 oC, t i c analysis of the reaction mixture indicated the presence of numerous polar unidentified components and one re lat ive ly non-polar component (Rf - 0.40) ( s i l i c a gel , development with 9:1 petroleum ether-diethyl ether). Column chromatography of the black o i l on s i l i c a gel afforded a product (36% y ie ld ) , which was subsequently identi f ied as compound (143). The spectral data derived from (143) were found to be in f u l l accord with the assigned structure. For example, the nmr spectrum of (143) showed, in addition to the methylene protons, a 9-proton singlet at 8 0.16 (2J_Sn-H " 5 o ^z), a 3-proton singlet at 8 3.68, a 1-proton multiplet in the region 8 4.71-4.73 and a 1-proton multiplet in the region 6 4.78-4.81. In addition, high resolution mass spectrometry ver i f ied that the molecular formula of (143) is C 1 3 H 2 2 0 2 S n . The stereochemical configuration of (143) was unequivocally established by performing nOe difference experiments. For example, i rradiat ion of the singlet at 8 3.68 (-OMe) caused signal enhancement at 6 0.16 (-SnMe 3), while irradiat ion of the singlet at 8 0.16 (-SnMe3) caused signal enhancement at 8 3.68 (-OMe) and 6 4.78-4.81 (vinyl proton). Efforts were made to increase the y i e ld of (134), but these were not successful. For example, when the above reaction was repeated in CH3CN or PhH, t i c analysis of the reaction mixture indicated the presence of polar, unidentified material. Similarly, repeating the reaction (equation 80) i n THF using sources of Pd(0) such as a mixture of palladium(II) acetate, triethylamine and triphenylphosphine resulted in a mixture of unidentified components. - 166 -EXPERIMENTAL I. General Melting points were determined using a Fisher-Johns melting point apparatus and are uncorrected. Boil ing points were recorded as air-bath temperatures required for bulb-to-bulb (Kugelrohr) d i s t i l l a t ions and are uncorrected. Infrared ( ir) spectra were obtained on l iqu id films or carbon tetrachloride solutions, employing a Perkin-Elmer model 1710 spectrophotometer (internal calibration) or a Perkin-Elmer model 710B spectrophotometer calibrated using the 1601 cm"1 band of a polystyrene f i lm. Proton nuclear magnetic resonance (^ H nmr) spectra were recorded on deuteriochloroform solutions or hexadeuteriobenzene solutions using Bruker Models WP-80, HXS-270, or WH-400 spectrometers or a Varian model XL-300 instrument. Carbon nuclear magnetic resonance ( 1 3 C nmr) and t i n nuclear magnetic resonance ( 1 1 9 S n nmr) were recorded on deuteriochloro-form solutions using a Varian model XL-300 instrument. Signal positions are given in 6 units and for ^H nmr were measured relative to tetramethylsilane (TMS) as the internal standard or to the chloroform signal (6" 7.25). 6^ The mul t ip l i c i ty , number of protons, coupling constants, and assignments (where possible) are indicated in parenthe-s i s . For compounds containing the a l l y l i c moiety the v inyl protons have been assigned as H A , Hg and H Q as depicted in the structure below. For - 167 -l-^C nmr 6 was measured relative to the deuteriochloroform signal (6 77.0)°^  and multiplicity was detrmined from APT experiments (atached proton test). For H^Sn nmr 5 was measured relative to tetramethylstan-nane (5=0.0)°^  as internal standard. Tin-hydrogen coupling constants (J_Sn.j) and tin-carbon coupling constants (J.Sn-c) a r e given as an average of the H^Sn and H^Sn values (unles  stated otherwise) . Tin-tin coupling constants (J.Sri-Sn) a r e §iven a s "^^Sn values. Low and high resolution mas spectra were recorded with Varin/MAT CH4B and/or Kratos/AEl MS50 mas spectrometers. Molecular weight determinations (high resolution mas spectrometry) in cases of compounds with tri-methylstannyl groups were based on 120gn (unxess stated otherwise) and were made on the (M+-CH3) peak. In cases of compounds containing trimethylgermyl groups, the measurements were based on ^4Ge and were made on the (M+-CH3) peak, while for compounds containing both a trimethylgermyl group and a tri-n-butylstannyl group, the measurements were made on ^20gn an(j 72Q6 o r o n 118gn an(j 74Q6 ancj w e r e made on the (M+'C^HQ) peak. Gas-liquid chromatography (glc) analyses were performed on Hewlet-Packard models 580 or 5890 capilary gas chromatographs using 25 m x 0.21 m  fused silica columns coated with cros-linked SE-54 and equipped with flame ionization detectors. Thin layer chromatography (tic) analyses were done on commercial aluminum-backed silica gel plates (E. Merck, Type 5554) or plastic backed silica gel plates (E. Merck, Type 5735). Visualization was acomplished with ultraviolet light, iodine, and/or by spraying the plate with 5% ammonium molybdate -10% aqueous sulfuric acid. Conven-- 168 -t ional column chromatography was done on 70-230 mesh s i l i c a gel (E. Merck) while flash column chromatography93 was done on 230-400 mesh s i l i c a gel (E. Merck). A l l compounds that were subjected to high resolution mass spectro-metry were homogeneous by t i c and glc analyses. Unless otherwise stated, a l l reactions were carried out under an atmosphere of dry argon using glassware that had been thoroughly flame-dried. Cold temperatures used for various reactions were obtained as follows: ice-acetone ( - 1 0 ° C ) , 27 g CaCl 2/100 mL H 2 0-C0 2 ( - 2 0 ° C ) , 46 g CaCl 2/100 mL H 2 0-C0 2 ( - 4 8 ° C ) , chloroform-C0 2 ( - 6 3 ° C ) , acetone-C0 2 ( -78°C) and methanol-N2 ( - 9 8 ° C ) . I I . Solvents and Reagents Solvents and reagents were purif ied and dried using established procedures . 9 4 Ether and THF were d i s t i l l e d from sodium benzophenone kety l . Triethylamine, diisopropylamine, HMPA, DMSO and DMF were d i s t i l l e d from calcium hydride. Methylene chloride and carbon tetra-chloride were d i s t i l l e d from P 205. Petroleum ether refers to the fract ion bo i l ing between 30-60°C. Hexamethylditin was obtained from Organometallics Inc. , while bromotrimethylgermane and tetrakistriphenylphosphinepalladium(O) were obtained either from Aldrich Chemical Co. Inc. or from Morton Thiokol, Inc. (Alfa Products) and were used without further puri f icat ion. - 169 -Solutions of methyllithium (low halide) in ether, n-butyllithium in hexane and diisobutylaluminum hydride in hexane were obtained from Aldrich Chemical Co. , Inc. and the former two reagents were standardized using the procedure of Kofron and Baclawski .^ Cuprous bromide-dimethyl sulfide complex was prepared by the method of H o u s e , 9 6 a after washing commercial cuprous bromide with methanol. 9 6* 5 Saturated aqueous ammonium chloride (pH 8) was prepared by the addition of 50 mL of aqueous ammonium hydroxide (58%) to 1 L of satu-rated aqueous ammonium chloride. Lithium diisopropylamide (IDA) was prepared by the addition of a solution of alkyll i thium in ether or hexane to a solution of diisopropy-lamine (1 equiv) in dry THF at -78°C. The resulting colorless solution was then s t i rred at 0°C for 10 min before being used. I I I . Preparation of Q,^-acetylenic esters General Procedure 1: Preparation of a.B-ace ty l en i c esters R—=====—C02R' To a cold ( - 7 8 ° C ) , s t irred solution of the appropriate 1-alkyne (1 equiv) in dry THF was added a solution of methyllithium (1.2 equiv) in ether. The result ing solution was s t irred at -78°C for 10-15 min, warmed to -20°C and s t i rred at this temperature for 1 h. Methyl or ethyl chloroformate (1.5 equiv) was added and the solution was s t irred - 170 -at -20°C for 1 h and at room temperature for 1 h. Saturated aqueous sodium bicarbonate and ether were added. The organic layer was separ-ated, washed with saturated aqueous sodium bicarbonate and brine and dried over anhydrous magnesium sulfate. Concentration, followed by puri f icat ion (column chromatography and/or d i s t i l l a t i on ) of the residual o i l afforded the appropriate ester. Preparation of 6-bromo-l-hexanol (92) To a s t i rred solution of 1,6-hexanediol (91) (5.0 g, 42.3 mmol) in 100 mL of dry benzene was added 6.76 mL (84.6 mmol) of 48% hydrogen bromide. A Dean Stark water trap was attached to the reaction flask and the mixture was refluxed for 23 h. The solution was washed with 50 mL of 6 M sodium hydroxide, 50 mL of 10% hydrochloric acid and 100 mL of brine and then was dried over anhydrous magnesium sulfate. Glc analysis of the solution showed that i t contained the monobromide (92) and the corresponding dibromide. Concentration, followed by column chromatogra-phy of the residual o i l on s i l i c a gel (20 g, elution i n i t i a l l y with petroleum ether and then with diethyl ether) and d i s t i l l a t i o n (air-bath temperature 5 8 - 6 0 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 5.834 g (70%) of the bromide (92). This colorless o i l exhibited i r (film): 3300 (br), 1450, 1060 cm' 1 ; X H nmr (270 MHz, CDC13) 6: 1.33-1.52 (m, 3H), 1.59 (quintet, 2H, J - 7 Hz), 1.89 (quintet, 2H, BrCH 2 CH 2 - , J = 7 - 171 -Hz), 3.42 (t, 2H, BrCH 2 - , J = 7 Hz), 3.65 (t, 2H, -CH2OH, J - 7 Hz). Exact Mass calcd. for C 6 H n 8 1 B r (M+^O): 164.0025; found: 164.0021. Preparation of 6-bromohexanal (93) To a s t i rred solution of pyridinium chlorochromate (6.1 g, 28.30 mmol) and sodium acetate (0.58 g, 7.07 mmol) in 25 mL of dry dichloro-methane was added a solution of 6-bromo-l-hexanol (92) (2.576 g, 14.15 mmol) in 55 mL of dry dichloromethane. The brown mixture was s t irred for 1.5 h at room temperature and then was poured into 300 mL of diethyl ether. The mixture was passed through a short column of F l o r i s i l (20 g, elution with diethyl ether). Concentration of the combined eluate, followed by d i s t i l l a t i o n (air-bath temperature 5 5 - 6 0 ° C / 0 . 0 5 Torr) of the residual o i l , afforded 1.76 g (69%) of the aldehyde (93). This colorless o i l exhibited i r (film): 2700, 1708, 1450, 1280 cm"1; -^H nmr (270 MHz, CDC13) 6: 1.39-1.55 (m, 2H), 1.58-1.72 (m, 2H), 1.87 (quintet, 2H, J - 7 Hz), 2.40 (td, 2H, -CH2CH0, J - 7, 1 Hz), 3.49 (t, 2H, -CH 2 Br, J - 7 Hz), 9.75 (t, IH, -CHO, J - 1 Hz). Exact Mass calcd. for C 6 H 1 0 7 9 B r (M+-1): 176.9916; found: 176.9919. H Br O - 172 -Preparation of 1.1.7-tribromo-l-heptene (94) Br Br Br To a s t i rred solution-suspension of triphenylphosphine (5.13 g, 19.5 mmol) in 100 mL of dry dichloromethane was added carbon tetrabromide (19.5 mmol) and zinc dust (19.5 mmol). After the reaction mixture had been s t i rred at room temperature for 23 h, a solution of 6-bromohexanal (93) (1.76 g, 9.77 mmol) in 20 mL of dry dichloromethane was added dropwise over a period of 20 min. The resulting burgandy suspension was s t i rred at room temperature for 2 h. Petroleum ether (350 mL) was added and the supernatant solution was decanted from the o i l . The o i l was taken up in 70 mL of dichloromethane, petroleum ether (350 mL) was added and the supernatant solution was again decanted. Concentration of the combined supernatant solutions, followed by d i s t i l l a t i o n (air-bath temperature 8 0 ° C / 0 . 0 5 Torr) of the residual o i l afforded 3.15 g (96%) of the tribromide (94). This colorless o i l exhibited i r (film): 1620, 1450, 800 cm -- 1; X H nmr (270 MHz, CDC13) 6: 1.41-1.56 (m, 4H), 1.81-1.95 (m, 2H), 2.08-2.19 (m, 2H), 3.41 (t, 2H, -CH 2 Br, J = 7 Hz), 6.40 (t, IH, v iny l proton, J 7 Hz). Exact Mass calcd. for C 7 H 1 1 8 1 B r 3 (M+) : 337.8354; found: 337.8354. Preparation of methyl 8-bromo-2-octvnoate (95) C0 2 M e - 173 -To a cold ( - 7 8 ° C ) , s t irred solution of 1,1,7-tribromo-l-heptene (94) (3.15 g, 9.319 mmol) in 120 mL of dry THF was added a solution of n-butyllithium (23.29 mmol) in hexane. The mixture was s t irred at -78°C for 1 h and at room temperature for 1 h. The solution was then cooled to -20°C, methyl chloroformate (10.25 mmol) was added, and the solution was s t i rred at -20°C for 1 h and at room temperature for 1 h. Workup as described in general procedure 1 followed by d i s t i l l a t i o n (air-bath temperature 9 0 ° C / 0 . 0 5 Torr) of the residual o i l , afforded 1.95 g (89%) of the ester (95). This colorless o i l exhibited i r (film): 2200, 1700, 1430, 1310-1200 (br), 1078 cm"1; X H nmr (270 MHz, C D C I 3 ) 6: 1.54-1.68 (m, 4H), 1.89 (quintet, 2H, BrCH 2 CH 2 - , J - 7 Hz), 2.38 (t, 2H, -CH 2f>C-C0 2Me, J = 7 Hz), 3.41 (t, 2H, BrCH 2 - , J - 7 Hz), 3.77 (s, 3H, -OMe). Exact Mass calcd. for C 8 H 1 0 O 8 1 B r (M+-0CH3): 202.9896; found: 202.9896. Preparation of 6-chlorohexanal (96) To a s t i rred solution of pyridinium chlorochromate (7.5 g, 34.8 mmol) and sodium acetate (0.71 g, 8.7 mmol) in 25 mL of dry dichloro-methane was added a solution of 6-chloro-l-hexanol (2.37 g, 17.4 mmol) in 35 mL of dry dichloromethane. The brown mixture was s t i rred for 1.45 h at room temperature and then was poured into 300 mL of diethyl ether. The mixture was passed through a short column of F l o r i s i l (20 g, elution H Cl O - 174 -with diethyl ether). Concentration of the combined eluate, followed by d i s t i l l a t i o n (air-bath temperature 6 0 - 6 5 ° C / 0 . 0 5 Torr) of the residual o i l , afforded 1.83 g (79%) of the aldehyde (96). This colorless o i l exhibited i r (film): 2700, 1708, 1455, 1300 cm"1; *H nmr (300 MHz, CDC13) 6: 1.41-1.59 (m, 2H), 1.60-1.75 (m, 2H), 1.82 (quintet, 2H, C1CH 2 CH 2 -, J - 7 Hz), 2.52 (td, 2H, -CH2CH0, J - 7, 1 Hz), 3.66 (t, 2H, -CH 2C1, J - 7 Hz), 9.80 (t, IH, -CHO, J - 1 Hz). Exact Mass calcd. for C 6 H 1 1 0 3 5 C 1 (M+-1): 133.0420; found: 133.0419. Preparation of 1.l-dibromo-7-chloro-l-heptene (97) To a s t i rred solution-suspension of triphenylphosphine (7.16 g, 27.3 mmol) in 120 mL of dry dichloromethane was added carbon tetrabromide (9.05 g, 27.3 mmol) and zinc dust (27.3 mmol). After the reaction mixture had been s t irred at room temperature for 24 h, a solution of 6-chlorohexanal (96) (1.83 g, 13.6 mmol) in 25 mL of dry dichloromethane was added dropwise over a period of 20 min. The resulting tan suspen-sion was s t i rred at room temperature for 2.5 h. Petroleum ether (400 mL) was added and the supernatant solution was decanted from the o i l . The o i l was taken up in 70 mL of dichloromethane, petroleum ether (300 mL) was added and the supernatant solution was again decanted. Concen-trat ion of the combined supernatant solutions, followed by d i s t i l l a t i o n (air-bath temperature 7 0 ° C / 0 . 0 5 Torr) of the residual o i l afforded 3.71 Br - 175 -g (94%) of the dibromoolefin (97). This colorless o i l exhibited i r (fi lm): 1610, 1440, 1210, 800 cm"1; 1 H nmr (300 MHz, CDC13) 6: 1.38-1.56 (m, 4H), 1.73-1.86 (m, 2H), 1.97-2.10 (m, 2H), 3.53 (t, 2H, -CH 2C1, J - 7 Hz), 3.75 (s, 3H, -OMe), 6.40 (t, IH, v iny l proton, J - 7 Hz). Exact Mass calcd. for C 7 H 1 1 7 9 B r 8 1 B r 3 5 C l (M+) : 289.8897; found: 289.8896. Preparation of methyl 8-chloro-2-octvnoate (98) To a cold ( - 7 8 ° C ) , s t irred solution of 1,l-dibromo-7-chloro-l-heptene (97) (3.71 g, 12.8 mmol) in 120 mL of dry THF was added a solution of n-butyllithium (28.1 mmol) in hexane. The reaction mixture was s t i rred at -78CC for 1 h and at room temperature for 1 h. The solution was then cooled to -20°C, methyl chloroformate (13.0 mmol) was added and the solution was s t irred at -20°C for 1 h and at room temperature for 1 h. Workup, as in general procedure 1, followed by d i s t i l l a t i o n (air-bath temperature 9 5 ° C / 0 . 0 5 Torr) of the residual o i l , afforded 2.131 g (89%) of the ester (98). This colorless o i l exhibited i r (f i lm): 2220, 1445, 1080 cm"1; X H nmr (270 MHz, CDCI3) 6: 1.55-1.67 (m, 4H), 1.80 (quintet, 2H, C1CH 2CH 2-, J - 7 Hz), 2.37 (t, 2H, - C H 2 O C - , J - 7 Hz), 3.53 (t, 2H, -CH 2C1, J - 7 Hz), 3.77 (s, 3H, -OMe). Exact  Mass calcd. for C g H 1 0 O 3 5 C l (M+-0CH3): 157.0416; 157.0418. - 176 -Preparation of methyl 8-iodo-2-octvnoate (99) ^=—C0 2 Me To a s t i rred solution of methyl 8-bromo-2-octynoate (95) (967 mg, 4.132 mmol) in 40 mL of acetone was added sodium iodide (2.48 g, 16.53 mmol). The solution was s t irred at reflux for 7.5 h. The solution was concentrated, petroleum ether (40 mL) and water (20 mL) were added to the residue, the organic layer was washed twice with water (15 mL) and then was dried over anhydrous magnesium sulfate. Concentration, followed by d i s t i l l a t i o n (air-bath temperature 8 0 - 8 5 ° C / 0 . 0 5 Torr) of the residual o i l afforded 1.08 g (93%) of the iodide (99). This colorless o i l exhibited i r (film): 2236, 1714, 1256 c m - 1 ; X H nmr (300 MHz, CDC13) 8: 1.50-1.70 (m, 4H), 1.88 (quintet, 2H, ICH 2 CH 2 - , J - 7.5 Hz), 2.49 (t, 2H, -CH2C=C-, J - 7.5 Hz), 3.22 (t, 2H, I C H 2 - , J - 7.5 Hz), 3.80 (s, 3H, -OMe). Exact Mass calcd. for C 9 H 1 3 0 2 I (M+) : 279.9962; found: 279.9965. Preparation of methyl 6-chloro-2-hexynoate (100) Following general procedure 1, to a cold ( - 7 8 ° C ) , s t i rred solution of 5-chloro-l-pentyne (3.3 g, 3.24 mmol) in 120 mL of dry THF was added a solution of methyllithium (4.12 mmol) in ether. The mixture was Cl - 177 -s t i rred at -78°C for 15 min and at -20°C for 1 h. Methyl chloroformate (4.54 mmol) was added and the solution was s t irred at -20°C for 1 h and for 1 h at 0°C. Normal workup, followed by d i s t i l l a t i o n (air-bath temperature 115-118°C/12 Torr) of the residual o i l afforded 4.654 g (90%) of the ester (100). This colorless o i l exhibited i r (film): 2230, 1700, 1250 (br); X H nmr (270 MHz, CDC13) 6: 2.05 (quintet, 2H, C1CH 2 CH 2 CH 2 -, J - 7 Hz), 2.55 (t, 2H, C1CH 2CH 2CH 2-, J - 7 Hz), 3.65 (t, 2H, C1CH 2 CH 2 CH 2 -, J - 7 Hz), 3.78 (s, 3H, -OMe). Exact Mass calcd. for C 7 H 9 0 2 C1 (M+): 160.0291; found: 160.0291. Preparation of methyl-6-bromo-2-hexynoate (101) / s . ^ =====—C02Me Br To a mixture of a solution of methyl 6-chloro-2-hexynoate (100) (510 mg, 2.712 mmol) in 1.5 mL of heptane and 1.5 mL of H 20 was added sodium bromide (1.39 g, 13.5 mmol) and Adogen 464® (-4 drops). The mixture was s t i rred at 100°C for 4.5 h. Glc analysis of the organic layer indicated the presence of 54% of the chloride (100) and 39% of the bromide (101). The aqueous layer was removed and 1.5 mL of H 2 0, sodium bromide (5 equiv) and Adogen 464® (-4 drops) were added to the organic solution. The mixture was s t i rred at 100°C for 5 h. Removal of the aqueous layer, addition of fresh H20-NaBr-Adogen 464®, and subsequent refluxing for 5 h was repeated two more times. Glc analysis of the organic layer at this stage indicated the presence of 93% of the bromide (101). Petroleum - 178 -ether (20 mL) was added, the organic layer was separated and washed three times with saturated aqueous ammonium chloride and then was dried over anhydrous magnesium sulfate. Concentration, followed by d i s t i l l a -t ion (air-bath temperature 6 5 ° C / 0 . 0 5 Torr) of the residual o i l afforded 402 mg (72%) of the bromide (101). This colorless o i l exhibited i r (fi lm): 2238, 1713, 1251 (br), 1079 c m - 1 ; X H nmr (270 MHz, CDC13) 6: 2.11 (quintet, 2H, BrCH 2 CH 2 - , J - 7 Hz), 2.56 (t, 2H, BrCH 2 CH 2 CH 2 - , J -7 Hz), 3.50 (t, 2H, BrCH 2 CH 2 CH 2 - , J - 7 Hz), 3.77 (s, 3H, -OMe). Exact  Mass calcd. for C 7 H 9 0 2 8 1 B r (M+): 205.9766; found: 205.9767. Preparation of methyl 6-iodo-2-hexvnoate (102) To a s t i rred solution of methyl 6-chloro-2-hexynoate (100) (780 mg, 4.875 mmol) in 20 mL of acetone was added sodium iodide (2.95 g, 19.5 mmol). The solution was s t irred at reflux for 16 h. The solution was concentrated, petroleum ether (30 mL) and water (20 mL) were added to the residue, the organic layer was washed twice with water (15 mL), and then was dried over anhydrous magnesium sulfate. Concentration, followed by d i s t i l l a t i o n (air-bath temperature 70"C/0.05 Torr) of the residual o i l afforded 1.12 g (91%) of the iodide (102). This colorless o i l exhibited i r (fi lm): 2240, 1713, 1262, 1078 cm"1; X H nmr (270 MHz, C D C I 3 ) 6: 2.04 (quintet, 2H, ICH 2 CH 2 CH 2 - , I - 7 Hz), 2.47 (t, 2H, ICH 2 CH 2 CH 2 - , J - 7 Hz), 3.27 (t, 2H, ICH 2 CH 2 CH 2 - , J - 7 Hz), 3.74 (s, - 179 -3H, -OMe). Exact Mass calcd. for C 7 H 9 0 2 I (M+): 251.9649; found: 251.9646. Preparation of ethvl 5-p-toluenesulfonvloxy-2-pentvnoate (103) C02Et To a s t i rred solution of ethyl 5-hydroxy-2-pentynoate (563 mg, 4.26 mmol) in 25 mL of dry CH2CI2 was added p_-toluenesulfonylchloride (1.21 g, 6.340 mmol), pyridine (0.69 mL, 8.53 mmol) and 4-dimethylaminopyri-dine (0.5 g, 4.1 mmol). The solution was s t irred at room temperature for 30 h. The solution was concentrated, petroleum ether (50 mL) was added to the residue and the organic solution was washed with 10% hydrochloric acid (20 mL), saturated aqueous sodium bicarbonate (20 mL), water (20 mL) and then was dried over anhydrous magnesium sulfate. Concentration, followed by flash column chromatography of the residual o i l on s i l i c a gel (20 g, elution with petroleum ether-ethyl acetate; 1:1) and d i s t i l l a t i o n (air-bath temperature 80°C/0.05 Torr) of the o i l thus obtained afforded 600 mg (47%) of the p . " t o l u e n e s u l f ° n a t e (103). This colorless o i l exhibited i r (film): 2247, 1713, 1365, 1260, 1177, 1080 cm"1; X H nmr (80 MHz, CDCI3) 6: 1.32 (t, 3H, -OCH 2CH 3 , J -=• 7 Hz), 2.50 (s, 3H, Jfe), 2.75 (t, 2H, -CH 2CH 2OTs, J - 7 Hz), 4.17 (t, 2H, -CH 2CH 2OTs, J - 7 Hz), 4.22 (q, 2H, -OCH 2CH 3 , J - 7 Hz), 7.37 (d, 2H, J We thank Mr. John Wai for a sample of this compound. - 180 -- 8 Hz), 7.72 (d, 2H, J - 8 Hz). Exact Mass calcd. for C 1 4 H 1 6 0 5 S (M+): 296.0718; found: 296.0714. Preparation of ethyl 5-bromo-2-pentynoate (104) To a s t i rred solution of the ester (103) (570 mg, 1.926 mmol) in 10 mL of dry DMF was added sodium bromide (0.6 g, 7.7 mmol). The solution was s t i rred at room temperature for 3 days. Water (10 mL) and petroleum ether (20 mL) were added and the aqueous layer was washed three times with petroleum ether (15 mL). The combined organic extracts were dried over anhydrous magnesium sulfate. Concentration, followed by d i s t i l l a -t ion (air-bath temperature 8 0 ° C / 0 . 0 5 Torr) of the residual o i l afforded 365 mg (90%) of the bromide (104). This colorless o i l exhibited i r (fi lm): 2241, 1713, 1256, 1075 cm"1; X H nmr (80 MHz, CDC13) 6: 1.30 (t, 3H, -OCH 2CH 3 , J - 7 Hz), 2.75-3.02 (m, 2H), 3.30-3.57 (m, 2H), 4.20 (q, 2H, -OCH 2CH 3 , J - 7 Hz). Exact Mass calcd. C 5 H 4 0 8 1 B r (M +-0CH 2CH 3): 158.9446; found: 158.9443. - 181 -Preparation of methyl 2.8-nonadlvnoate (106) and dimethyl 2.8-decadivndioate (107) H C0 2Me M e 0 2 C M e 0 2 C 106 107 Following general procedure 1, to a cold ( - 7 8 ° C ) , s t irred solution of commercially available 1,7-octadiyne (105) (2.542 g, 23.98 mmol) in 70 mL of dry THF was added a solution of methyllithium (31.17 mmol) in ether. After the reaction mixture had been s t irred at -78°C for 10 min and at -20°C for 1 h, methyl chloroformate (33.5 mmol) was added and the solution was s t irred at -20°C for 1 h and at room temperature for 1 h. Normal workup, followed by column chromatography of the residual o i l on s i l i c a gel (100 g, elution with petroleum ether-diethyl ether; 2:3) afforded two o i l s A and B. D i s t i l l a t i o n (air-bath temperature 100°C/ 0.05 Torr) of o i l A afforded 1.573 g (40%) of the monoester (106) as a colorless o i l . D i s t i l l a t i o n (air-bath temperature 1 6 0 ° C / 0 . 0 5 Torr) of o i l B afforded 1.709 g (32%) of the diester (107) as a white so l id . Compound (106) exhibited i r (film): 3296, 2238, 1718, 1436, 1260, 1080 cm"1; X H nmr (300 MHz, CDC13) 6: 1.60-1.81 (m, 4H), 1.98 (t, IH, acetylenic proton, J - 2 Hz), 2.23 (dt, 2H, HC=CCH2-, J - 7, 2 Hz), 2.39 (t, 2H, Me0 2CC«CCH 2-, J - 7 Hz), 3.76 (s, 3H, -OMe). Exact Mass calcd. for C 1 0 H n 0 2 (M+-1): 163.0759; found: 163.0757. Compound (107) exhibited; m.p. 34°C (from methanol-H20); i r (CC1 4): 2245, 1733, 1456, 1279, 1084cm- 1; X H nmr (300 MHz, C D C I 3 ) 5: 1.68-1.80 (m, 4H), 2.32-2.48 (m, 4H), 3.78 (s, 3H, -OMe). Exact Mass calcd. for - 182 -C 1 1 H 1 1 ° 3 (M+-0CH3): 191.0708; found: 191.0714. Preparation of methyl 8-bromonon-8-en-2-ynoate (108) B r C02Me To a cold ( 0 ° C ) , s t irred solution of B-bromo-9-borabicyclo[3.3.1]-nonane (4.02 mL, 4.02 mmol) in 5 mL of dry dichloromethane was added dropwise, over a period of 10 min, a solution of methyl 2,8-nonadiynoate (106) (300 mg, 1.83 mmol) in 5 mL of dry dichloromethane. After the reaction mixture had been s t irred at 0°C for 3 h, 1 mL of acetic acid was added. The solution was s t irred at 0°C for a further 1 h and then aqueous sodium hydroxide (3 M, 12 mL) and aqueous hydrogen peroxide (30%, 2 mL) were added and the mixture was s t i rred at room temperature for 30 min. The mixture was extracted three times with petroleum ether (20 mL). The combined extracts were successively washed with water (15 mL), saturated aqueous sodium bicarbonate (15 mL) and water (15 mL) and then were dried over anhydrous magnesium sulfate. Concentration, followed by column chromatography of the residual o i l on s i l i c a gel (15 g, elution with petroleum ether-diethyl ether; 4:1) and d i s t i l l a t i o n (air-bath temperature 1 3 0 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 388 mg (87%) of the v iny l bromide (108). This colorless o i l exhibited i r (fi lm): 2238, 1718, 1631, 1435, 1261, 1079 cm- 1 ; X H nmr (270 MHz, CDC13) 6: 1.54-1.72 (m, 4H), 2.36 (t, 2H, J = 7 Hz), 2.44 (t, 2H, J - 7 Hz), 3.76 (s, 3H,-0Me), 5.41 (d, IH, J = 1.5 Hz), 5.58 (d, IH, - 183 -J - 1.5 Hz). Exact Mass calcd. for C 9 H 1 0 o 8 l B r (M +-OCH 3): 214.9896; found: 214.9894. Preparation of methyl 2.6-heptadlvnoate (109) and dimethyl  2.6-octadivndioate (110) H — - M e 0 2 C — = v. Following general procedure 1, to a cold ( - 7 8 ° C ) , s t irred solution of 1,5-hexadiyne (1.718 g, 22 mmol) in 120 mL of dry THF was added a solution of methyllithium (28.6 mmol) in ether. After the reaction mixture had been s t irred at -78°C for 15 min and at -20°C for 1 h, methyl chloroformate (30.8 mmol) was added and the solution was s t irred at -20°C for 1 h and at room temperature for 1 h. Normal workup, followed by column chromatography of the residual o i l on s i l i c a gel (90 g, elution with petroleum ether-diethyl ether; 2:3) afforded two o i l s , A and B. D i s t i l l a t i o n (air-bath temperature 9 0 - 9 3 ° C / 2 0 Torr) of o i l A afforded 1.073 g (36%) of the monoester (109) as a colorless o i l . D i s t i l l a t i o n (air-bath temperature 1 1 5 ° C / 0 . 0 5 Torr) of o i l B afforded 1.707 g (40%) of the diester (110) as a white so l id . Compound (109) exhibited i r (film): 3295, 2333, 1713, 1435, 1338-1100 (br), 1078 cm' 1 ; lH nmr (300 MHz, CDC13) 6: 2.08 (t, IH, acetylenic proton, J - 2 Hz), 2.44-2.52 (m, 2H), 2.55-2.62 (m, 2H), 3.78 (s, 3H, -OMe). Exact Mass calcd. for C 8 H 7 0 2 (M+-1): 135.0446; found: 1 09 - 184 -135.0448. Compound (110) exhibited, m.p. 63-64°C (from H20-methanol); i r (CC1 4): 2237, 1733, 1435, 1300-1200 (br), 1077 cm"1; X H nmr (300 MHz, CDCI3) 8: 2.64 (s, 4H, methylene protons), 3.79 (s, 6H, -OMe). Exact  Mass calcd. for C 1 0 H 1 0 0 4 (M+) : 194.0579; found: 194.0574. Preparation of methyl 6-hepten-2-ynoate (111) To a s t i rred solution of the monoester (109) (1.065 g, 7.83 mmol) in 50 mL of hexane was added 10% palladium-on-barium sulfate (106 mg) and the reaction vessel was connected to a hydrogenation apparatus. After 2.15 h glc analysis of an aliquot indicated that the starting material had been consumed. Concentration, followed by column chromatography of the residual o i l on s i l i c a gel (20 g, elution with petroleum ether-diethyl ether; 17:1) and d i s t i l l a t i o n (air-bath temperature 90°C/20 Torr) of the o i l thus obtained, afforded 789 mg (73%) of the alkene (111). This colorless o i l exhibited i r (film): 3081, 2332, 1718, 1643, 1258, 921 cm' 1 ; X H nmr (300 MHz, CDCI3) 6: 2.28-2.48 (m, 4H), 3.73 (s, 3H, -OMe), 5.06 (dd, IH, Hg, J - 10, 2 Hz), 5.10 (dd, IH, H A , J = 17, 2 Hz), 5.83 (ddt, IH, H c , J = 17, 10, 6 Hz). Exact Mass calcd. for C 7 H 7 0 (M+-OCH3): 107.0497; found: 107.0504. - 185 -Preparat ion of d i e t h y l 2.7-nonadiyndioate (112) Et0 2 C ^ = Fol lowing general procedure 1, to a c o l d ( - 7 8 ° C ) , s t i r r e d s o l u t i o n of 1,6-heptadiyne (928 mg, 10 mmol) i n 60 mL of dry THF was added a s o l u t i o n of methy l l i th ium (14 mmol) i n e ther . A f t e r the r e a c t i o n mixture had been s t i r r e d at - 7 8 ° C for 10 min and at -20 ° C f o r 40 min, e t h y l chloroformate (15 mmol) was added and the s o l u t i o n was s t i r r e d at -20 ° C for 30 min and at room temperature for 30 min. Normal workup, fo l lowed by column chromatography of the r e s i d u a l o i l on s i l i c a ge l (100 g, e l u t i o n wi th petroleum e t h e r - d i e t h y l e ther , 1:1) a f forded two o i l s , A and B. D i s t i l l a t i o n ( a i r - b a t h temperature 1 3 2 - 1 3 7 ° C / 0 . 0 5 T o r r ) of o i l A af forded 1.28 g (57%) of the d i e s t e r ( 1 1 2 ) . This c o l o r l e s s o i l exh i -b i t e d i r ( f i l m ) : 2239, 1713, 1251-1173 (br ) ; X H nmr (400 MHz, C D C 1 3 ) 6: 1.32 ( t , 6H, OCH2CH3, J = 7 Hz) , 1.87 (quintet , 2H, methylene protons , J - 7.5 Hz) , 2.5 ( t , 4H , methylene protons , J = 7.5 Hz) , 4.22 (q, 4 H , - O C H 2 C H 3 , J «=• 7 Hz) . Exact Mass c a l c d . f or C 1 2 H 1 6 ° 4 (M+'OC^CT^): 179.0708; found: 179.0714. 1 - 186 -IV. Synthesis of a lky l (Z)- and (E)-2,3-bis(trimethylstannyl)-2-alkenoates and (E)-N,N-dimethyl)-2,3-bis(trimethylstannyl)-2-alkenamides General Procedure 2: Preparation of alkyl (Z)-2.3-bis(trimethyl- stannyl) -2-alkenoates (83) To a s t i rred solution of the appropriate acetylenic ester (1 equiv) in dry THF (-15 mL per mmol) was added hexamethylditin (1 equiv) followed by Pd(PPh3)4 (0.009-0.02 equiv) and the mixture was s t i rred at room temperature or under reflux for 4-62 h. Concentration of the solution gave a brown-black o i l , which was chromatographed (to remove any residual hexamethylditin and insoluble material) on a short path column of s i l i c a gel (elution with petroleum ether-diethyl ether) y ie lding, after concentration of the appropriate fractions, a colorless o i l . The o i l was then subjected to a vacuum of 0.05 Torr for 1-2 h at room temperature. Me 3Sn SnMe 3 R C0 2R' - 187 -General Procedure 3: Preparation of alkvl (E)-2.3-bis(trimethyl-stannyl) -2-alkenoates (78) Me3Sn C02R' R SnMe3 To a one-necked, round bottomed flask containing a condenser was added the appropriate a lkyl (Z)-2,3-bis(trimethylstannyl)-2-alkenoate and the sample was heated to 75-95°C for 6-48 h. The yellow o i l was then either d i s t i l l e d direct ly (receiving bulb cooled to -10°C, 0.1 Torr) or was subjected to flash column chromatography on s i l i c a gel (elution with petroleum ether-diethyl ether) prior to d i s t i l l a t i o n . The resultant a lkyl (E)-2,3-bis(trimethylstannyl)-2-alkenoate was thus obtained as a colorless o i l . Preparation of ethvl (Z)- and (E)-2.3-bis(trimethylstannyl)-2-butenoate  (124) and (77) Me3Sn SnMe3 Me3Sn C0 2Et Me C0 2Et Me SnMe3 124 77 Following general procedure 2, to a s t i rred solution of ethyl-2-butynoate (70) (344 mg, 3.07 mmol) in 45 mL of dry THF was added hexamethylditin (3.07 mmol) and (PPh 3) 4Pd (50 mg, 0.043 mmol). The - 188 -mixture was s t irred at room temperature for 4 h. Concentration, followed by column chromatography of the residual brown o i l on s i l i c a gel (30 g, elution with petroleum ether-diethyl ether; 19:1) and subjection of the o i l thus obtained to vacuum (0.05 Torr; 1.5 h) afforded, 1.29 g (95%) of the (Z) isomer (124). This colorless o i l exhibited i r (film): 1702, 1200, 1040, 775 cm"1; X H nmr (80 MHz, CDC13) 6: 0.22 (s, 9H, -SnMe.3, 2 J S n . H - 52.5 Hz), 0.25 (s, 9H, -SnMe.3, 2J_Sn-H " 53.5 Hz), 1.27 (t, 3H, -OCH 2CH 3 , J - 7 Hz), 2.07 (s, 3H, v iny l methyl, 4 J S n - H - 10 Hz, 3 J S n _ H " 4° Hz), 4.15 (q, 2H, -OCH 2CH 3 , J_ - 7 Hz); 1 3 C nmr (75.6 MHz, CDCI3) 6: -7.2 (q, ^Sn-C = 3 2 6 H z > • - ° - 8 <1» l j -Sn-C = 342 Hz), 14.5 (q), 26.4 (q, 2 I S n - C = 6 2 H z > 3 j-Sn-C " 7 1 H z > , 60.1 (t) , 149.9 (s), 159.8 (s), 171.7 (s). Exact Mass calcd. for C n H 2 3 0 2 S n 2 (M + -CH 3 ): 426.9743; found: 426.9743. Following general procedure 3, the ester (124) (78 mg, 0.176 mmol) was converted, after s t i r r ing at 79°C for 30 h, into the bis(trimethyl-stannyl) ester (77). Flash column chromatography of the crude product on s i l i c a gel (5 g, elution with petroleum ether-diethyl ether; 17:1) followed by d i s t i l l a t i o n (air-bath temperature 7 0 - 7 5 ° C / 0 . 1 Torr) of the o i l thus obtained, afforded 64 mg (82%) of the (E) isomer (77). This colorless o i l exhibited i r ( f i lm) : 1685, 1230, 775 c m - 1 ; 1 H nmr (80 MHz, CDCI3) 6: 0.14 (s, 9H, -SnMe.3, 2 J S n - H " 5 3 Hz), 0.25 (s, 9H, -SnMe.3, 2 j-Sn-H ~ 5 4 H z )> 1 - 2 8 3 H . -OCH 2CH 3 , J - 7 Hz), 2.22 (s, 3H, v iny l methyl, 4 J S n - H " 1 1 Hz, 3 I S n - H " 4 9 Hz), 4.17 (q, 2H, -OCH 2CH 3 , J - 7 Hz); 1 3 C nmr (75.6 MHz, CDCI3) 6: -6.7 (q, ^sn-C " 3 4 4 Hz>> " 5 - 9 ( l . l j -Sn-C - 3 3 9 Hz), 14.3 (q), 28.2 (q, 2 J S n . C = 62 Hz - 3 J S n . C ) . 60.8 (t) , - 189 -144.2 (s), 171.6 (s), 180.9 (s). Exact Mass calcd. for C 1 1 H230 2 Sn 2 (M+-CH3): 426.9743; found: 426.9740. Preparation of methyl (Z)- and (E)-2 .3-bis (trimethylstannyl')-2- pentenoate (125) and (147) Me3Sn SnMe3 Me3Sn C02Me H H Et C02Me Et SnMe3 125 147 Following general procedure 2, to a s t irred solution of methyl 2-pentynoate (114) (1.13 g, 9.94 mmol) in 150 mL of dry THF was added hexamethylditin (9.94 mmol) and (PPh 3) 4Pd (130 mg, 0.113 mmol). The mixture was s t i rred at room temperature for 18 h. Concentration, followed by column chromatography of the resultant black o i l on s i l i c a gel (40 g, elution with petroleum ether-diethyl ether; 19:1) and subjection of the o i l thus obtained to vacuum (0.05 Torr, 2 h) , afforded 3.88 g (88%) of the ( Z ) isomer (125). This colorless o i l exhibited i r (fi lm): 1708, 1191, 771 c m - 1 ; lH nmr (270 MHz, CDC13) 6: 0.21 (s, 9H, -SnMe.3, 2 j-Sn-H " 5 2 Hz>> 0 2 2 <s> 9 H> -SnMe.3, 2 J S n . H - 54 Hz), 1.00 (t, 3H, -CH 2 CH 3 , J - 7 Hz), 2.35 (q, 2H, -CH 2 CH 3 , J - 7 Hz), 3.69 (s, 3H, -OCH3); 1 3 C nmr (75.6 MHz, CDCI3) 6: -6.8 (q, ^ s n - C " 3 3 5 H z ) > " 6 - 7 <<1. l j -Sn-C " 3 3 2 H z >. 1 4 - 7 CO. 3 4 - ° 2^Sn-C " 57 Hz, 3 J S n . c - 68 Hz), 51.0 ( t ) , 148.2 (s), 166.8 (s), 172.3 (s). Exact Mass calcd. for c l l H 2 3 ° 2 S n 2 (M + -CH 3 ) : 426.9742; found: 426.9747. - 190 -Following general procedure 3, the ester (125) (71 mg, 0.16 mmol) was converted, after stirring at 85°C for 18 h, into the bis(trimethyl-stannyl) ester (147). Flash column chromatography of the crude o i l on sil i c a gel (5 g, elution with petroleum ether-diethyl ether; 17:1) followed by distillation (air-bath temperature 90-95°C/0.05 Torr) of the o i l thus obtained, afforded 58 mg (82%) of the (E) isomer (147). This colorless o i l exhibited i r (film): 1693, 1224, 772 cm"1; XH nmr (400 MHz, CDC13) 6: 0.18 (s, 9H, -SnMe.3, 2 J S n . H -= 52 Hz), 0.26 (s, 9H, -SnMe.3, 2J S n-H - 54 Hz), 0.98 (t, 3H, -CH2CH3, J - 7 Hz), 2.49 (q, 2H, -CH2CH3, J - 7 Hz), 3.70 (s, 3H, -OMe); 1 3C nmr (75.6 MHz, CDCI3) 6: -6.6 (q, ^ s n . c = 342 Hz), -6.1 (q, ^Sn-C = 3 4 0 H z> - 1 4 - 8 <<!>. 3 4 - 5 <1. 2 J S n _ c - 57 Hz - 3 J S n - c ) . 51.7 (t). 1 4 3 • 4 (s), 172.3 (s), 185.6 (s); 1 1 9Sn nmr (111.8 MHz, CDCI3) 5: -50.79 (s, J S n-Sn * 5 6 2 H z ) • -51,07 (s, J S n . S n - 562 Hz). Exact Mass calcd. for C1;]H2302Sn2 (M+-CH3): 426.9742; found: 426.9741. Preparation of methyl (Z)- and (E)-2.3-bis(trimethylstannyl)-4-methyl-2- pentenoate (126) and (148) Following general procedure 2, to a stirred solution of methyl 4-methyl-2-pentynoate (115) (856 mg, 6.848 mmol) in 90 mL of dry THF was added hexamethylditin (6.848 mmol) and (PPh3)4Pd (79 mg, 0.068 mmol). - 191 -The mixture was stirred at room temperature for 28 h. Concentration, followed by column chromatography of the resultant brown o i l on s i l ica gel (35 g, elution with petroleum ether-diethyl ether; 9:1) and subjec-tion of the o i l thus obtained to vacuum (0.05 Torr; 1 h), afforded 2.82 g (90%) of the (Z) isomer (126). This colorless o i l exhibited i r (film): 1705, 1190, 770 cm - 1; 1 H nmr (400 MHz, CDC1 3) 6: 0.25 (s, 9H, -SnMe3, 2 J S n _ H - 53.5 Hz), 0.28 (s, 9H, -SnMe.3, 2 J S n . H - 51 Hz), 1.04 (d, 6H, -CH(CH 3) 2, J - 6.5 Hz), 2.77 (septet, IH, -CH(CH 3) 2, J - 6.5 Hz), 3.68 (s, 3H, -OMe); 1 3 C nmr (75.6 MHz, CDCI3) 6: -6.3 (q, ^sn-C -340 Hz), -4.5 (q, ^Sn-C - 3 3 7 H z >. 2 2 - 7 <q. 3j-Sn-C " 1 2 - 8 Hz, 4 j-Sn-C " 6 Hz), 40.3 (d, 2 J S n . C " 5 2 Hz, 3ISn-C " 6 5 H z>• 50.9 <q)• 1 4 6 • 6 <s)-170.9 (s), 172.8 (s). Exact Mass calcd. for C 1 2 H 2 50 2 Sn 2 (M+-CH3): 440.9899; found: 440.9909. Following general procedure 3, the ester (126) (417 mg, 0.914 mmol) was converted into the bis(trimethylstannyl) ester (148) after stirring at 80°C for 6 h. Distillation of the crude o i l (air-bath temperature, 90-95°C/0.05 Torr) afforded 407 mg (98%) of the (E) isomer (148). This colorless o i l exhibited i r (film): 1688, 1220, 775 cm"1; % nmr (300 MHz, CDCI3) 6: 0.20 (s, 9H, -SnMe3, 2 J S n - H " 5 2 - 7 H z)> ° - 2 3 <s> 9H> -SnMe.3, 2 j-Sn-H ~ 5 3 - 7 Hz>> 1 - 1 0 <d> 6 H - -CH(CH3) 2, J - 7 Hz), 2.66 (septet, IH, -CH(CH 3) 2, J - 7 Hz), 3.68 (s, 3H, -OMe); 1 3 C nmr (75.6 MHz, CDCI3) 6: -6.2 (q, ^sn-C - 3 ^ Hz), -4.4 (q, ^ s ^ c - 337 Hz), 22.1 (q, 3 J S n - C " 1 3 Hz, 4 J S n - C - 6.4 Hz), 43.1 (d, 2 J S n . c - 51 Hz, 3j-Sn-C " 5 9 Hz), 51.5 (q), 143.7 (s), 172.7 (s), 184.2 (s); 1 1 9 S n nmr (111.8 MHz, CDCI3) 6: -44.56 (s, J S n -Sn = 512 Hz), -60.22 (s, I S n -Sn -- 192 -512 Hz). Exact Mass calcd. for C 1 2 H 2 5 ° 2 S n 2 (M +"CH 3): 440.9898; found: 440.9896. Preparation of methyl (Z)- and (E)-2.3-bis(trimethvlstannyl)-3-cyclo- propyl-2-propenoate (127) and (149) Following general procedure 2, to a s t irred solution of methyl 3-cyclopropyl-2-propynoate (117) (304 mg, 2.45 mmol) in 40 mL of dry THF was added hexamethylditin (2.45 mmol) and (PPh 3) 4Pd (50 mg, 0.043 mmol). The mixture was s t irred at room temperature for 36 h. Concentration, followed by column chromatography of the resultant brown o i l on s i l i c a gel (20 g, elution with petroleum ether-diethyl ether; 9:1) and subjec-tion of the o i l thus obtained to vacuum (0.05 Torr; 1 h), afforded 916 mg (83%) of the (Z) isomer (127). This colorless o i l exhibited i r (fi lm): 1703, 1200, 770 cm' 1 ; X H nmr (270 MHz, CDC13) 6: 0.23 (s, 18H, 2x-SnMe3), 2J_Sn-H " 5 4 H z > • 0.40-0.48 (m, 2H), 0.66-0.76 (m, 2H), 1.73 (tt , IH, J - 8.5, 5.5 Hz), 3.70 (s, 3H, -OMe). Exact Mass calcd. for c 1 2 H 2 3 ° 2 S n 2 (M+-CH3): 438.9742; found: 438.9743. Following general procedure 3, the ester (127) (412 mg, 0.910 mmol) was converted into the bis(trimethylstannyl) ester (149) after s t i r r ing at 85°C for 7 h. D i s t i l l a t i o n of the crude o i l (air-bath temperature, - 193 -1 0 0 ° C / 0 . 0 5 Torr) afforded 344 mg (83%) of the (E) isomer (149). This colorless o i l exhibited i r (film): 1685, 1220, 775 cm' 1 ; ^ nmr (400 MHz, CDC13) S: 0.17 (s, 9H, -SnMe.3, 2J_Sn-H ** 5 4 H z ) > ° - 2 6 <s> 9 H> -SnMe3, 2 J S n - H " 5 6 H z >• 0.53-0.59 (m, 2H), 0.83-0.91 (m, 2H), 1.78 (tt , IH, J - 8.5, 5.5 Hz), 3.68 (s, 3H, -OMe). Exact Mass calcd. for c 1 2 H 2 3 ° 2 S n 2 (M+-CH3): 438.9742; found: 438.9745. Preparation of methyl (Z)- and (E)-2.3-bis(trimethylstannyl)-7-tert- butvldimethvlsiloxv-2-heptenoate (128) and (150) Following general procedure 2, to a s t irred solution of methyl 7-tert-butyldimethylsiloxy-2-heptynoate (118) (625 mg, 2.3 mmol) in 40 mL of dry THF was added hexamethylditin (2.3 mmol) and (PPlvj^Pd (26 mg, 0.023 mmol). The mixture was s t irred at room temperature for 62 h. Concentration, followed by column chromatography of the resultant black o i l on s i l i c a gel (40 g, elution with petroleum ether-diethyl ether; 19:1) and subjection of the o i l thus obtained to vacuum (0.05 Torr, 1 h), afforded 1.13 g (82%) of the (Z) isomer (128). This colorless o i l exhibited i r (fi lm): 1702, 1200, 1100, 840, 740 cm"1; X H nmr (400 MHz, CDCI3) 6: 0.05 (s, 6H, B ^ M ^ S i - ) , 0.24 (s, 9H, -SnMe.3, 2 j-Sn-H = 5 2 H z > • 0.25 (s, 9H, -SnMe.3, 2 j-Sn-H " 5 4 H z > • ° - 8 9 <s> 9 H> Bu t Me 2 Si- ) , 1.36-1.45 - 194 -(m, 2H), 1.46-1.55 (m, 2H), 2.35 (t, 2H, a l l y l i c protons, J - 8 Hz, 3 J S n . H - 60 Hz), 3.60 (t, 2H, Bu t Me 2 SiOCH 2 - , J - 8 Hz), 3.70 (s, 3H, -OMe); 1 3 C nmr (75.6 MHz, CDC13) 6: -6.77 (q, ^ s n - C " 3 3 8 Hz>> " 6 - 6 9 (q. ^Sn-C " 3 3 1 H z >- " 5 - 2 1 8 - 3 <s>> 2 5 - 9 2 6 - 5 3 2 - 7 40.9 (t, 2 J _ S n . c - 55 Hz, 3 J S n . c - 66 Hz), 51.0 (t) , 62.9 (q) , 148.8 (s), 165.3 (s), 172.3 (s); 1 1 9 S n nmr (111.8 MHz, CDCI3) 6: -36.47 (s, I S n-Sn = 334 Hz), -37.15 (s, J_Sn-Sn " 3 3 4 H z > • Exact Mass calcd. for c 1 9 H 4 1 ° 3 s i l l 8 s n l 2 ° S n (M*-^): 583.0863; found: 583.0858. Following general procedure 3, the ester (128) (427 mg, 0.71 mmol) was converted into the bis(trimethylstannyl) ester (150) after s t i r r i n g at 95°C for 12 h. D i s t i l l a t i o n of the yellow o i l (air-bath temperature 1 6 0 ° C / 0 . 0 5 Torr) afforded 402 mg (94%) of the (E) isomer (150). This colorless o i l exhibited i r (film): 1686, 1225, 1100, 840, 770 cm' 1 ; X H nmr (400 MHz, CDC13) 6: 0.04 (s, 6H, B^Me^Si-), 0.15 (s, 9H, -SnMe3, 2J-Sn-H ~ 5 4 H z )> ° - 2 5 (s, 9H, -SnMe.3, 2J_Sn-H " 5 4 H z > - ° - 8 9 <s> 9 H> Bu t Me 2 Si - ) , 1.29-1.40 (m, 2H), 1.50-1.59 (m, 2H), 2.44-2.51 (m, 2H, a l l y l i c protons, 3J_sn-H " 6 0 H z ) • 3 - 6 1 2 H> Bu t Me 2 Si0CH 2 - , J - 8 Hz), 3.70 (s, 3H, -OMe); 1 3 C nmr (75.6 MHz, CDC13) 5: -6.6 (q, ^ s n - C " 3 4 3 Hz), -6.1 (q, ^Sn-C = 3 3 2 H z > » " 5 - 3 <<1> • 1 8 • 3 <s> < 2 5 - 9 W • 2 7 - ° <C> > 32.9 ( t ) , 41.6 (t, 2 J S n - C - 55 Hz - 3 J_ S n -C>. 5 1 - 7 ( t ) • 6 2 ' 9 ' 1 4 3 • 8 (s), 172.2 (s), 184.4 (s); 1 1 9 S n nmr (111.8MHz, CDCI3) 6: -50.15 (s, J.Sn-Sn - 562 Hz), -51.54 (s, J_sn-Sn " 562 Hz). Exact Mass calcd. for c 1 9 H 4 1 ° 3 s i S n 2 (M+-CH3): 585.0869; found: 585.0876. - 195 -Preparation of methyl (Z)- and (E)-2.3-bis(trimethylstannyl)-6-tetra- hvdropvranvloxv-2-hexenoate (129) and (151) Following general procedure 2, to a s t irred solution of methyl 6-tetrahydropyranyloxy-2-hexynoate (119) (365 mg, 1.6 mmol) in 30 mL of dry THF was added hexamethylditin (1.6 mmol) and (PPh 3) 4Pd (18 mg, 0.015 mmol). The mixture was s t irred at room temperature for 15 h. Concen-trat ion, followed by column chromatography of the resultant brown o i l on s i l i c a gel (20 g, elution with petroleum ether-diethyl ether; 1:1) and subjection of the o i l thus obtained to vacuum (0.05 Torr, 2 h), afforded 734 mg (83%) of the (Z) isomer (129). This colorless o i l exhibited i r (film): 1700, 1190, 1030, 780 c m - 1 ; X H nmr (400 MHz, CDC13) 6: 0.25 (s, 9H, -SnMe3, 2 J_s n -H = 5 4 H z > • ° - 2 6 <s • 9 H - -SnMe3, 2J_s n-H = 5 2 H z ) > 1.47-1.74 (m, 7H), 1.77-1.89 (m, IH), 2.35-2.47 (m, 2H, a l l y l i c pro-tons), 3.38 (dt, IH, J = 10, 6.5 Hz), 3.46-3.53 (m, IH), 3.66-3.74 (m, IH), 3.70 (s, 3H, -OMe), 3.82-3.89 (m, IH), 4.58 (t, IH, methine proton, J = 3 H z ) . Exact Mass calcd. for C 1 7 H 3 3 0 4 S n 2 (M+-CH;}): 541.0423; found: 541.0425. Following general procedure 3, the ester (129) (705 mg, 1.27 mmol) was converted into the bis(trimethylstannyl) ester (151) after s t i r r ing at 80°C for 6 h. D i s t i l l a t i o n of the crude o i l (air-bath temperature - 196 -1 5 5 ° C / 0 . 0 5 Torr) afforded 652 mg (93%) of the (E) isomer (151). This colorless o i l exhibited i r (film): 1686, 1190, 1030, 780 cm' 1 ; *H nmr (400 MHz, CDC13) 6: 0.17 (s, 9H, -SnMe.3, l j -Sn-H " 5 4 H z > - ° - 2 5 <s • 9H> -SnMe.3, ^Sn-H " 5 5 H z > • 1-48-1.65 (m, 6H), 1.67-1.76 (m, IH), 1.79-1.90 (m, IH), 2.51-2.62 (m, 2H, a l l y l i c protons), 3.41 (dt, IH, J - 10, 7 Hz), 3.47-3.55 (m, IH), 3.70 (s, 3H, -OMe), 3.75 (dt, IH, J - 10, 7 Hz), 3.82-3.90 (m, IH), 4.6 (t, IH, methine proton, J - 4 Hz). Exact Mass calcd. for C 1 7 H 3 3 0 4 S n 2 (M+-CH3): 541.0423; found: 541.0426. Preparation of methyl (Z)- and (E)-2.3-bis(trimethylstannyl)-4-tert- butyldimethylsiloxv-2-butenoate (130) and (152) Following general procedure 2, to a s t i rred solution of ethyl 4-tert-butyldimethylsiloxy-2-butynoate (116) (205 mg, 0.847 mmol) in 13 mL of dry THF was added hexamethylditin (0.847 mmol) and (PPl^^Pd (13 mg, 0.011 mmol). The mixture was s t irred at 55-60°C for 4 h. Concentration, followed by column chromatography of the resultant brown o i l on s i l i c a gel (10 g, elution with petroleum ether-diethyl ether; 9:1) and subjection of the o i l thus obtained to vacuum (0.05 Torr, 1 h), afforded 403 mg (83%) of the (Z) isomer (130). This colorless o i l exhibited i r (fi lm): 1698, 1170, 1060, 840, 770 cm"1; ^ nmr (270 MHz, CDCI3) 6: 0.03 (s, 6H, B^Me^Si-), 0.20 (s, 9H, -SnMe.3, 2^Sn-H " 5 6 Hz>> 130 152 - 197 -0.23 (s, 9H, -SnMe3, 2 J S n . H - 56 Hz), 0.87 (s, 9H, Bu t Me 2 Si- ) . 1-26 (t, 3H, - 0 C H 2 C H 3 , J - 7 Hz), 4.10 (q, 2H, -OCH 2CH 3 , J - 7 Hz), 4.35 (s, 2H, Bu t Me 2 SiOCH 2 - , 3 J S n - H - 40 Hz, 4 J S n - H ~ 1 1 Hz>> 1 3 c n m r (75.6 MHz, C D C 1 3 ) 6: -6.5 (q, - 345 Hz), -5.8 (q, - 337 Hz) , -5.3 (q), 14.5 (q), 18.4 (s), 26.0 (q), 60.1 (t) , 68.0 (t, 2 J S n . c - 35 Hz, 3J-Sn-C - 76 Hz), 147.1 (s) , 166.1 (s) , 171.6 (s). Exact Mass calcd. for C 1 7 H 3 7 0 3 S i S n 2 (M+-CH5): 557.0556; found: 557.0549. Following general procedure 3, the ester (130) (162 mg, 0.283 mmol) was converted into the bis(trimethylstannyl) ester (152) after s t i r r i n g at 81°C for 12 h. Flash column chromatography of the yellow o i l on s i l i c a gel (10 g, elution with petroleum ether-diethyl ether; 97:3) followed by d i s t i l l a t i o n (air-bath temperature 1 3 5 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 140 mg (86%) of the (E) isomer (130). This colorless o i l exhibited i r (film): 1698, 1640, 1230, 845, 780 cm"1; 1 H nmr (270 MHz, CDCI3) 6: 0.06 (s, 6H, Bu t Me 2 SiO-), 0.15 (s, 9H, -SnMe.3, 2 J S n _ H •= 54 Hz), 0.24 (s, 9H, -SnMe.3, 2^Sn-H = 50 Hz), 0.89 (s, 9H, Bu t Me 2 SiO-), 1.26 (t, 3H, - 0 C H 2 C H 3 , J •= 7 Hz), 4.11 (q, 2H, -OCH 2CH 3 , J = 7 Hz), 4.34 (s, 2H, Bu t Me 2 SiOCH 2 - , 3 J S n . H - 44 Hz, 4 J S n - H " 1 1 Hz>> 1 3 C nmr (75.6 MHz, CDCI3) 5: -6.1 (q, -"-Jsn-C " 3 4 5 H z > • " 6 - 0 l j -Sn-C - 342 Hz), -5.1 (q), 14.2 (q), 18.2 (s), 26.0 (q), 60.8 (t) , 69.9 (t, 2 j-Sn-C " 4 1 H z - 3 j-Sn-C = 6 1 H z > . 1 4 4 - 9 <s>. 1 7 1 - 9 <s>. 1 7 7 - 4 <s> • 1 1 9 s n nmr (111.8 MHz, CDCI3) 6: -47.06 (s, J.sn-Sn " 510 Hz), -48.80 (s, I S n - S n - 510 Hz). Exact Mass calcd. for C 1 7 H 3 7 0 3 S i S n 2 (M+-CH3): 557.0556; found: 557.0556. - 198 -Preparation of methyl (Z)- and (E)-2.3-bis(trimethylstannyl)-5-(2-cvclo- pentenyl)-2-pentenoate (131) and (153) Me3Sn SnMe3 Me3Sn C02Me C02Me SnMe3 Following general procedure 2, to a s t irred solution of methyl 5-(2-cyclopentenyl)-2-pentynoate (120) (122 mg, 0.685 mmol) in 15 mL of dry THF was added hexamethylditin (0.685 mmol) and (PPl^^Pd (8 mg, 0.007 mmol). The reaction mixture was s t irred at reflux for 6 h. Concentration, followed by column chromatography of the resultant o i l on s i l i c a gel (5 g, elution with petroleum ether-diethyl ether; 17:3) and subjection of the o i l thus obtained to vacuum (0.05 Torr, 45 min), afforded 255 mg (73%) of the (Z) isomer (131). This colorless o i l exhibited i r (film): 1700, 1200, 770 c m - 1 ; X H nmr (400 MHz, CDC13) 5: 55 Hz), 1.29-1.50 (m, 4H), 1.97-2.08 (m, IH), 2.20-2.40 (m, 4H), 2.59-2.69 (m, IH), 3.70 (s, 3H, -OMe), 5.63-5.75 (m, 2H, v iny l protons). Exact  Mass calcd. for C 1 6 H 2 9 0 2 S n 2 (M+'C^): 493.0212; found: 493.0216. 0.23 (s, 9H, -SnMe.3, 2 J S n - H "* 5 4 H z > • ° - 2 4 ( s - 9H> -SnMe.3, 2 J S n . H Following general procedure 3, the ester (131) (158 mg, 0.311 mmol) was converted into the bis(trimethylstannyl) ester (153) after s t i r r ing at 80°C for 8 h. D i s t i l l a t i o n of the o i l (air-bath temperature 1 3 0 ° C / 0 . 0 5 Torr) afforded 128 mg (81%) of the (E) isomer (153). This colorless o i l exhibited i r (film): 1685, 1225, 775 c m - 1 ; X H nmr (400 - 199 -MHz, CDCI3) 6: 0.15 (s, 9H, -SnMe.3, 2 J S n . H - 54 Hz), 0.25 (s, 9H, -SnMe.3, 2 J S n . H - 54 Hz), 1.24-1.40 (m, 2H) , 1.40-1.51 (m, IH), 2.00-2.11 (m, IH), 2.22-2.41 (m, 2H), 2.46-2.56 (m, 2H), 2.74-2.83 (m, IH), 3.70 (s, 3H, -OMe), 5.66-5.87 (m, 2H, v iny l protons); 1 1 9 S n nmr (111.8 MHz, CDCI3) 6: -50.24 ( J S n - S n " 564 Hz), -51.82 (s, J S n . S n " 564 Hz). Exact  Mass calcd. for C 1 6 H 2 90 2 Sn2 (M+-CH3): 493.0212; found: 493.0218. Preparation of methyl (Z)- and (E)-2.3-bis(trimethylstannyl)-4-(3-cvclo- hexenvl)-2-butenoate (132) and (154) Following general procedure 2, to a s t i rred solution of methyl 4-(3-cyclohexenyl)-2-butynoate (121) (89 mg, 0.5 mmol) in 8 mL of dry THF was added hexamethylditin (0.5 mmol) and (PPt^^Pd (8 mg, 0.007 mmol). The reaction mixture was s t irred at reflux for 6 h. Concentra-t ion, followed by column chromatography of the resultant o i l on s i l i c a gel (5 g, elution with petroleum ether-diethyl ether; 17:3) and subjec-t ion of the o i l thus obtained to vacuum (0.05 Torr, 45 min), afforded 188 mg (74%) of the (Z) isomer (132). This pale yellow o i l exhibited i r (fi lm): 1703, 1640, 1190, 780 cm"1; X H nmr (400 MHz, CDCI3) 6: 0.18 (s, 9H, -SnMe.3, 2 J S n - H " 5 1 • 5 H z> • °- 2 0 <s- 9H> -SnM§.3. 2 ISn-H " 53.5 Hz), 1.07-1.19 (m, IH), 1.51-1.72 (m, 3H), 1.88-2.06 (m, 3H), 2.21-2.38 (m, 2H), 3.63 (s, 3H, -OMe), 5.58-5.62 (m, 2H, v iny l i c protons); 1 3 C nmr - 200 -(75.6 MHz, CDCI3) 6: -6.6 (q, ^Sn-C ~ 3 4 0 Hz), * 6 - 5 ^Sn-C = 3 3 1 Hz), 25.4 (t) , 28.3 (t) , 31.5 (t) , 33.9 (d, 3 J S n . c - 6.6 Hz), 47.7 (t, 2^Sn-C ~ 53 Hz, 3 J S n - C = 6 5 Hz), 50.9 (q), 126.5 (d), 126.8 (d), 149.9 (s), 163.7 (s), 172.4 (s). Exact Mass calcd. for C 1 6 H 2 9 0 2 S n 2 (M+'C^): 493.0212; found: 493.0209. Following general procedure 3, the ester (132) (170 mg, 0.335 mmol) was converted into the bis(trimethylstannyl) ester (154) after s t i r r i n g at 88°C for 48 h. D i s t i l l a t i o n of the pale yellow o i l (air-bath temperature 1 5 0 ° C / 0 . 0 5 Torr) afforded 150 mg (88%) of the (E) isomer (154). This colorless o i l exhibited i r (film): 1685, 1640, 1220, 775 c m - 1 ; X H nmr (400 MHz, CDCI3) 6: 0.10 (s, 9H, -SnMe.3, 2 J S n - H = 52.5 Hz), 0.20 (s, 9H, -SnMe.3, 2 J S n - H " 54 Hz), 1.07-1.20 (m, IH), 1.58-1.71 (m, 3H), 1.90-2.05 (m, 3H), 2.36-2.53 (m, 2H), 3.65 (s, 3H, -OMe), 5.55-5.65 (m, 2H, v i n y l i c protons); 1 3 C nmr (75.6 MHz, CDCI3) 5: -6.2 (q, ^ s n - C " 342 Hz), -5.5 (q, ^ s n - C " 3 4 0 H z >• 2 5 - 4 <c>• 2 8 - 4 • 3 1 - 7 ^ • 3 4 - 2 <d> 3 j-Sn-C = 7 Hz), 47.8 (t, 3 J S n - C = 52 Hz - 2 J S n - c ) . 51.7 (q), 126.3 (d), 127.1 (d), 144.7 (s), 171.7 (s), 184.2 (s). Exact Mass calcd. for c 1 6 H 2 9 ° 2 S n 2 (W^-O^): 493.0212; found: 493.0206. - 201 -Preparation of methyl (Z)- and CE)-2.3-bis(trimethylstannyl)-2.6-hepta- dienoate (133) and (155) Following general procedure 2, to a s t i rred solution of methyl 6-hepten-2-ynoate (111) (350 mg, 2.53 mmol) in 39 mL of dry THF was added hexamethylditin (2.53 mmol) and (PPt^^Pd (52 mg, 0.045 mmol). The reaction mixture was s t irred at reflux for 4 h. Concentration, followed by column chromatography of the resultant black o i l on s i l i c a gel (20 g, elution with petroleum ether-diethyl ether; 17:3) and subjection of the o i l thus obtained to vacuum (0.05 Torr, 1 h) , afforded 1.003 g (85%) of the (Z) isomer (135). This colorless o i l exhibited i r (fi lm): 1708, 1641, 1191, 770 cm"1; -^H nmr (400 MHz, CDC13) 6: 0.24 (s, 9H, -SnMe.3, 2 J S n - H = 5 2 H z ) • ° - 2 4 5 ( s . 9H, -SnMe.3, 2 J S n - H = 5 4 H z > • 2 - n (broad qd, 2H, CH 2CHCH 2CH 2-, J - 7, 1.5 Hz), 2.38-2.45 (m, 2H, CH 2CHCH 2CH 2-), 3.69 (s, 3H, -OMe), 4.95 (ddt, IH, H B , J - 10, 2, 1.5 Hz), 5.01 (ddt, IH, H A , J - 17, 2, 1.5 Hz), 5.80 (ddt, IH, H c , J - 17, 10, 7 Hz); 1 3 C nmr (75.6 MHz, CDCI3) 6: -6.8 (q, ^ S n - C ~ 3 3 9 Hz>> -6.7 (q, ^ s n - c - 3 3 2 H z > . 3 4 - 3 3 iSn-C - 8 Hz), 40.3 (t, 2 J S n . C - 55 Hz, 3 J S n - C - 66 Hz), 50.9 (q), 114.7 (d), 137.6 (t) , 149.6 (s), 164.5 (s), 172.1 (s). Exact Mass calcd. for C 1 3 H 2 5 0 2 S n 2 (M+-CH3): 452.9899; found: 452.9896. Following general procedure 3, the ester (135) (155 mg, 0.33 mmol) was converted into the bis(trimethylstannyl) ester (155) after s t i r r i n g 1 55 - 202 -at 80°C for 14 h. Flash column chromatography of the yellow o i l on s i l i c a gel (5 g, elution with petroleum ether-diethyl ether; 17:3) followed by d i s t i l l a t i o n (air-bath temperature 9 5 - 1 0 0 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 125 mg (81%) of the (E) isomer (155). This colorless o i l exhibited i r (film): 1692, 1641, 1229, 770 cm"1; X H nmr (400 MHz, CDC13) 6: 0.16 (s, 9H, -SnMe.3, 2^Sn-H " 5 3 H z > > ° - 2 6 <s> 9H, -SnMe.3, 2 J S n . H - 54 Hz), 2.05 (qd, 2H, CH 2CHCH 2CH 2-, J - 7, 1.5 Hz), 2.53-2.61 (m, 2H, CH 2CHCH 2CH 2-), 3.70 (s, 3H, -OMe), 5.00 (ddt, IH, H B , J - 10, 2, 1.5 Hz), 5.04 (ddt, IH, H A , J = 17, 2, 1.5 Hz), 5.69 (ddt, IH, H c , J - 17, 10, 7 Hz); 1 3 C nmr (75.6 MHz, CDCI3) 6: -6.5 (q, -"-Jsn-C - 344 Hz), -6.0 (q, ^ s n . c - 340 Hz), 34.4 (t, 3 J S n - C c 8 Hz), 40.8 (t, 3 J S n . c - 55 Hz - 2 J S n - c ) . 51.8 (q), 115.0 (d), 137.0 (t) , 144.6 (s), 172.1 (s), 183.7 (s); 1 1 9 S n nmr (111.8MHz, CDCI3) 6: -50.96 (s, I S n-Sn - 551 Hz), -51.62 (s, J_sn-Sn = 551 Hz). Exact Mass calcd. for c 1 3 H 2 5 ° 2 S n 2 ( M 4 " - ^ ) : 452.9898; found: 452.9907. Preparation of methvl (Z)- and (E)-2.3-bis(trimethylstannyl)-8-bromo- 2.8-nonadienoate (134) and (156) To a s t i rred solution of palladium(II)acetate (2.7 mg, 3 mol%) in 1 - 203 -mL of dry THF was added triphenylphosphine (6.4 mg, 6 mol%) and triethy-lamine (114 jiL, 0.816 mmol). After the mixture had been s t irred at 60°C for 1 h hexamethylditin (0.408 mmol) and a solution of methyl 8-bromo-non-8-en-2-ynoate (108) (100 mg, 0.408 mmol) in 1 mL of dry THF was added to the red solution. The resulting yellow solution was s t i rred at reflux for 2 h. Concentration, followed by column chromatography of the resultant black o i l on s i l i c a gel (10 g, elution with petroleum ether-diethyl ether; 9:1) and subjection of the o i l thus obtained to vacuum (0.05 Torr, 45 min), afforded 149 mg (64%) of the (Z) isomer (134). This colorless o i l exhibited i r (film): 1708, 1630, 1191, 770 cm* 1; X H nmr (400 MHz, CDC13) 6: 0.23 (s, 9H, -SnMe.3, 2 J S n - H _ 5 3 H z)> ° - 2 5 (s> 9H, -SnMe.3, 2 j-Sn-H " 5 5 H z)> 1-22-1.32 (m, 2H) , 1.55 (quintet, CH 2 CBrCH 2 CH 2 - , J - 8 Hz), 2.35 (t, 2H, CH 2 CBr(CH 2 ) 3 CH 2 - , J - 8 Hz), 2.42 (t, 2H, CH 2 CBrCH 2 - , J = 8 Hz), 3.70 (s, 3H, -OMe), 5.39 (d, IH, v iny l i c proton, J - 2 Hz), 5.56 (d, IH, v iny l i c proton, J - 2 Hz); 1 3 C nmr (75.4 MHz, CDCI3) 6: -6.75 (q, ^ s n - C - 338 Hz), -6.67 (q, ^ s ^ c - 330 Hz), 27.6 (t) , 28.8 (t, 3 J S n - C =7.6 Hz), 40.6 (t, 2 J S n . c -= 55 Hz, 3 j-Sn-C " 6 6 H z >- 4 i - l ( O , 51.0 (q), 116.5 (d), 134.2 (d), 149.2 (s), 164.9 (s), 172.2 (s). Exact Mass calcd. for C 1 5 H 2 8 0 2 7 9 B r S n 2 (M+-CH3): 558.9317; found: 558.9312. Following general procedure 3, the ester (134) (80 mg, 0.139 mmol) was converted into the bis(trimethylstannyl) ester (156) after s t i r r i n g at 83°C for 36 h. Flash column chromatography of the pale yellow o i l on s i l i c a gel (10 g, elution with petroleum ether-diethyl ether; 9:1) followed by d i s t i l l a t i o n (air-bath temperature 1 4 5 ° C / 0 . 0 5 Torr) of the - 204 -o i l thus obtained, afforded 53 mg (66%) of the (E) isomer (156). This colorless o i l exhibited i r (film): 1691, 1630, 1226, 770 c m - 1 ; -^H nmr (400 MHz, CDC13) 5: 0.17 (s, 9H, -SnMe.3, 2 j-Sn-H " 5 2 H z > • ° - 2 7 <s> 9 H> -SnMe 3, 2 I S n - H " 5 4 H z ) . 1-26-1.37 (m, 2H), 1.60 (quintet, 2H, CH 2CBrCH 2CH 2 , J - 8 Hz), 2.39-2.53 (m, 4H, a l l y l i c protons), 3.70 (s, 3H, -OMe), 5.41 (d, IH, v iny l i c proton, J - 1.5 Hz), 5.57 (d, IH, v i n y l i c proton, J - 1.5 Hz); 1 3 C nmr (75.4 MHz, CDCI3) 6: -6.5 (q, l j -Sn-C " 3 4 1 H z ) . - 6 - 0 <q. l j -Sn-C ~ 3 4 0 H z ) - 2 7 - 8 <fc> • 2 9 - 2 <*> . 4 1 - 3 <t. 3 j-Sn-C - 55 Hz - 3 J S n -C>> 5 1 - 7 (O- 1 1 6 - 7 (d>• 1 3 4 - 2 (d>- 1 4 4 - 2 ( s). 172.1 (s), 183.8 (s). Exact Mass calcd. for C 1 5 H 2 8 0 2 8 1 B r S n 2 (M + -CH 3 ): 560.9298; found: 560.9306. Preparation of ethvl (Z)-2.3-bis(trimethylstannyl)-5-chloro-2- pentenoate (135) Following general procedure 2, to a s t irred solution of ethyl 5-chloro-2-pentynoate (122) (742 mg, 4.64 mmol) in 60 mL of THF was added hexamethylditin (4.64 mmol) and (PPI^^Pd (65 mg, 0.056 mmol). The mixture was s t i rred at reflux for 6 h. Concentration, followed by column chromatography of the resultant crude o i l on s i l i c a gel (35 g, elution with petroleum ether-diethyl ether; 23:2) and subjection of the o i l thus obtained to vacuum (0.05 Torr; 1.5 h), afforded 2.02 g (89%) of Cl - 205 -the (Z) isomer (135). This colorless o i l exhibited i r (film): 1702, 1186, 773 c m - 1 ; X H nmr (400 MHz, CDC13) 6: 0.27 (s, 9H, -SnMe.3, 2^Sn-H " 56 Hz), 0.28 (s, 9H, -SnMe.3, 2 J S n . H - 54 Hz), 1.31 (t, 3H, -OCH 2CH 3 , J -7 Hz), 2.79 (t, 2H, C1CH 2CH 2-, J - 8 Hz, 3 I S n . H - 54 Hz), 3.52 (t, 2H, C1CH 2 CH 2 -, J - 8 Hz), 4.19 (q, 2H, -0CH 2 CH 3 , J - 7 Hz). Exact Mass calcd. for C 1 2 H 2 4 0 2 3 5 C l S n 2 (M+-CH3): 474.9509; found: 474.9530. Preparation of ethvl (Z)-2.3-bis(trimethvlstannvl)-5-bromo-2- pentenoate (136) Me 3 Sn SnMe, C0 2 Et Br Following general procedure 2, to a s t i rred solution of ethyl 5-bromo-2-pentynoate (104) (347 mg, 1.69 mmol) in 20 mL of THF was added hexamethylditin (1.69 mmol) and (PPh 3) 4Pd (39 mg, 0.034 mmol). The mixture was s t i rred at reflux for 8 h. Concentration, followed by column chromatography of the resultant black o i l on s i l i c a gel (20 g, elution with petroleum ether-diethyl ether; 9:1) and subjection of the o i l thus obtained to vacuum (0.05 Torr; 1 h), afforded 600 mg (66%) of the (Z) isomer (136). This colorless o i l exhibited i r (fi lm): 1698, 1186, 770 c m - 1 ; X H nmr (270 MHz, CDCI3) 6: 0.26 (s, 9H, -SnMe.3, 2 J S n - H -56 Hz), 0.28 (s, 9H, -SnMe3, 2 J_s n -H " 54 Hz), 1.28 (t, 3H, -0CH 2 CH 3 , J -7 Hz), 2.84 (t, 2H, BrCH 2 CH 2 - , J - 8 Hz), 3.32 (t, 2H, BrCH 2 CH 2 - , J - 8 Hz), 4.15 (q, 2H, -0CH 2 CH 3 , J - 7 Hz). Exact Mass calcd. for C 1 2 H 2 4 0 2 8 1 B r S n 2 (M + -CH 3 ): 520.8985; found: 520.8982. - 206 -Preparation of methyl (Z)- and (E)-2.3-bis(trimethylstannyl)-6-chloro-2- hexenoate (137) and (146) Following general procedure 2, to a s t irred solution of methyl 6-chloro-2-hexynoate (100) (1.00 mg, 6.25 mmol) in 80 mL of THF was added hexamethylditin (6.25 mmol) and (PPl^^Pd (72 mg, 0.062 mmol). The mixture was s t i rred at reflux for 5 h. Concentration, followed by column chromatography of the resultant black o i l on s i l i c a gel (40 g, elution with petroleum ether-diethyl ether; 19:1) and subjection of the o i l thus obtained to vacuum (0.05 Torr; 2 h), afforded 2.62 g (86%) of the (Z) isomer (137). This colorless o i l exhibited i r (film): 1698, 1195, 770 cm"1; X H nmr (400 MHz, CDCI3) 6: 0.25 (s, 9H, -SnMe.3, 2 J S n . H = 54 Hz), 0.26 (s, 9H, -SnMe.3, 2 j-Sn-H ~ 5 1 Hz) • 1 > 8 5 (quintet, 2H, C1CH 2 CH 2 CH 2 - , J - 8 Hz), 2.47 (t, 2H, C1CH 2CH 2CH 2-, J = 8 Hz, 3 J S n - H " 55 Hz), 3.51 (t, 2H, C1CH 2CH 2CH 2-, J - 8 Hz), 3.70 (s, 3H, -OMe); In a nOe difference experiment, irradiat ion at 6 3.70 (-OMe) caused signal enhancement at 5 0.25 (aSnMe.3); 1 3 C nmr (75.6 MHz, CDCI3) 6: -6.74 (q, ^Sn-C " 3 3 7 H z )> " 6 - 6 9 <q- l j -Sn-C " 3 3 3 Hz), 3 2 - 8 3 j-Sn-C " 7 Hz), 38.2 (t, 2 J S n . C - 55 Hz, 3 J S n - C " 6 6 Hz), 44.4 (t) , 51.1 (q), 150.8 (s), 163.2 (s), 172.1 (s); 1 1 9 S n nmr (111.8 MHz, CDCI3) 6: -35.26 (s, J S n . S n - 317 Hz), -35.46 (Isn-Sn " 3 1 7 H z >• Exact Mass calcd. for C 1 2 H 2 4 0 2 3 5 C l S n 2 (M+-CH3): 474.9509; found: 474.9518. - 207 -Following general procedure 3, the ester (137) (477 mg, 0.973 mmol) was converted into the bis(trimethylstannyl) ester (146) after s t i r r ing at 75°C for 24 h. D i s t i l l a t i o n of the pale yellow o i l (air-bath temperature 1 0 5 ° C / 0 . 1 Torr) afforded 457 mg (96%) of the (E) isomer (146). This colorless o i l exhibited i r (film): 1685, 1220, 775 cm"1; X H nmr (400 MHz, CDC13) S 0.17 (s, 9H, -SnMe.3, 2 J S n - H - 54 Hz), 0.26 (s, 9H, -SnMe3, 2 J S n _ H - 55 Hz), 1.73-1.82 (m, 2H, C1CH 2CH 2CH 2-), 2.60-2.66 (m, 2H, C1CH 2CH 2CH 2-, 3 J_s n -H " 6 0 Hz>> 3 - 5 5 (t> 2 H , C1CH 2 CH 2 CH 2 -, J - 7 Hz), 3.71 (s, 3H, OMe): In a nOe difference experiment, i rradiat ion at 5 3.71 (-OMe) caused signal enhancement at 6 0.17 (-SnMe.3) and 6 0.26 (-SnMe.3); 1 3 C nmr (75.6 MHz, CDCI3) 6: -6.4 (q, ^ s ^ c - 346 Hz), -6.0 ( l j-Sn-C ~ 341 Hz), 33.0 (t, 3 J S n . c = B Hz), 39.0 (t, 2 J S n . c - 55 Hz = 3 ^Sn-c)- 4 4 - 3 51.8 (q), 145.5 (s) , 172.0 (s), 182.3 (s); 1 1 9 S n nmr (111.8 MHz, CDCI3) 5: -49.29 (s, J S n - S n " 527 Hz), -50.17 (s, J S n . S n " 527 Hz). Exact Mass calcd. for C 1 2 H 2 4 0 2 3 5 C l S n 2 (M+-CH3): 474.9509; found: 474.9510. Preparation of methyl (Z)-2.3-bis(trimethylstannvl)-6-bromo-2- hexenoate (138) Br Following general procedure 2, to a s t irred solution of methyl 6-bromo-2-hexynoate (101) (644 mg, 3.14 mmol) in 40 mL of THF was added - 208 -hexamethylditin (3.14 mmol) and (PPl^^Pd (50 mg, 0.043 mmol). The mixture was s t i rred at reflux for 6 h. Concentration, followed by column chromatography of the resultant crude o i l on s i l i c a gel (30 g, elution with petroleum ether-diethyl ether; 19:1) and subjection of the o i l thus obtained to vacuum (0.05 Torr; 1.5 h) , afforded 1.41 g (84%) of the (Z) isomer (138). This colorless o i l exhibited i r (film): 1700, 1200, 780 cm"1; nmr (400 MHz, CDC13) 6: 0.25 (s, 9H, -SnMe.3, 2 j-Sn-H " 55 Hz), 0.26 (s, 9H, -SnMe.3, 2 J S n . H - 54 Hz), 1.93 (quintet, 2H, BrCH 2 CH 2 CH 2 - , J - 7.5 Hz), 2.47 (t, 2H, BrCH 2 CH 2 CH 2 - , J - 7.5 Hz, 3 J S n - H - 55 Hz), 3.38 (t, 2H, BrCH 2 CH 2 CH 2 - , J - 7.5 Hz), 3.71 (s, 3H, -OMe). Exact Mass calcd. for C 1 2 H 2 4 0 2 8 1 B r S n 2 (M + -CH 3 ): 520.8985; found: 520.8988. Preparation of methyl (Z)-2.3-bis(trimethylstannyl)-6-iodo-2-hexenoate Following general procedure 2, to a s t i rred solution of methyl 6-iodo-2-hexynoate (102) (756 mg, 3.0 mmol) in 45 mL of dry THF was added hexamethylditin (3.0 mmol) and (PPl^^Pd (75 mg, 0.06 mmol). The mixture was s t i rred at reflux for 6 h. Concentration, followed by column chromatography of the resultant black o i l on s i l i c a gel (50 g, elution with petroleum ether-diethyl ether; 23:2) and subjection of the (139) - 209 -o i l thus obtained to vacuum (0.05 Torr; 1.5 h), afforded 1.37 g (79%) of the (Z) isomer (139). This colorless o i l exhibited i r (fi lm): 1705, 1190, 771 cm"1; X H nmr (400 MHz, CDC13) 6: 0.245 (s, 9H, -SnMe.3, 2 J S n - H - 56 Hz), 0.25 (s, 9H, -SnMe3, 2 J S n . H - 54 Hz), 1.91 (quintet, 2H, ICH 2 CH 2 CH 2 - , 1 - 8 Hz), 2.42 (t, 2H, ICH 2 CH 2 CH 2 - , J = 8 Hz, 3 J S n - H - 56 Hz), 3.15 (t, 2H, ICH 2 CH 2 CH 2 - , J - 8 Hz), 3.71 (s, 3H, -OMe). Exact  Mass calcd. for C 1 2 H 2 4 0 2 I S n 2 (M+-CH3): 566.8867; found: 566.8882. Preparation of methyl (Z)- and (E)-2.3-bis(trimethylstannyl)-7-bromo-2- heptenoate (140) and (157) Following general procedure 2, to a s t irred solution of methyl 7-bromo-2-heptynoate (123) (600 mg, 2.74 mmol) in 40 mL of dry THF was added hexamethylditin (2.74 mmol) and (PPl^^Pd (50 mg, 0.043 mmol). The mixture was s t i rred at reflux for 5 h. Concentration, followed by column chromatography of the resultant black o i l on s i l i c a gel (45 g, elution with petroleum ether-diethyl ether; 19:1) and subjection of the o i l thus obtained to vacuum (0.05 Torr; 1.5 h) , afforded 1.17 g (78%) of the (Z) isomer (140). This colorless o i l exhibited i r (film): 1698, 1290, 770 cm' 1 ; X H nmr (400 MHz, CDCI3) 6: 0.25 (s, 18H, 2 x -SnMe.3, 2 J S n - H - 54 Hz), 1.48-1.57 (m, 2H), 1.86 (quintet, 2H, J - 7 Hz), 2.36 - 210 -(t, 2H, a l l y l i c protons, J - 7 Hz, 3 Isn-H ~ 5 7 H z ) • 3 - 4 0 2 H> BrCH 2 - , J - 7 Hz), 3.70 (s, 3H, -OMe); 1 3 C nmr (75.6 MHz, CDC13) 6: -6.8 (q, l j -Sn-C " 3 4 2 H z > . - 6 - 7 <q- l j-Sn-C " 3 2 7 H z > . 2 8 - 3 (t, 3J-Sn-C " 8 H z > • 32.3 ( t ) , 33.6 (t) , 39.8 (t, 2 J S n . c - 55 Hz, 3 J S n - C " 6 6 H z ) . 51.0 (q), 149.7 (s), 164.4 (s), 172.1 (s). Exact Mass calcd. for C 1 3 H 2 6 0 2 7 9 B r S n 2 (M + -CH 3 ) : 534.9141; found: 534.9148. Following general procedure 3, the ester (140) (101 mg, 0.184 mmol) was converted into the bis(trimethylstannyl) ester (157), after s t i r r i n g 40 h at 85°C. Flash column chromatography of the pale yellow o i l on s i l i c a gel (10 g, elution with petroleum ether-diethyl ether; 17:1) followed by d i s t i l l a t i o n (air-bath temperature 1 3 0 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 81 mg (80%) of the (E) isomer (157). This colorless o i l exhibited i r (film): 1692, 1224, 770 cm' 1 ; X H nmr (400 MHz, CDC13) 6: 0.17 (s, 9H, -SnMe3, 2 J S n . H - 52.5 Hz), 0.26 (s, 9H, -SnMe 3, 2 J S n - H ~ 53.5 Hz), 1.42-1.52 (m, 2H), 1.91 (quintet, 2H, J •= 7 Hz), 2.47-2.54 (m, 2H, a l l y l i c protons, 3 J S n - H = 59 Hz), 3.42 (t, 2H, BrCH 2 CH 2 - , J . - 7 Hz), 3.71 (s, 3H, -OMe); 1 3 C nmr (75.6 MHz, CDC13) 8: -6.5 (q, i jgn.c = 341 Hz), -6.0 (q, l j S n _ c = 340 Hz), 28.9 (t, 3 J S n . c = 7.1 Hz), 32.7 (t) , 33.3 (t) , 40.7 (t, 2 J S n - C - 54 Hz - 3 J S n - c ) . 51.8 (q), 144.6 (s), 172.0 (s), 183.5 (s). Exact Mass calcd. for C 1 3 H 2 6 0 2 7 9 B r S n 2 (M+-CH3): 532.9161; found: 532.9164. - 211 -Preparation of methyl (Z)- and (E)-2 . 3-bis (trimethylstannyl')-8-bromo-2- octenoate (141) and (158) Following general procedure 2, to a s t irred solution of methyl 8-bromo-2-octynoate (95) (931 mg, 3.978 mmol) in 55 mL of dry THF was added hexamethylditin (3.978 mmol) and (PPl^^Pd (73 mg, 0.063 mmol). The mixture was s t irred at reflux for 16 h. Concentration, followed by column chromatography of the resultant black o i l on s i l i c a gel (30 g, elution with petroleum ether-diethyl ether; 9:1) and subjection of the o i l thus obtained to vacuum (0.05 Torr; 2 h), afforded 1.852 g (83%) of the (Z) isomer (141). This colorless o i l exhibited i r (film): 1707, 1191, 771 cm"1; X H nmr (400 MHz, CDCI3) 8: 0.24 (s, 9H, -SnMe.3, 2 J S n _ H -52 Hz), 0.25 (s, 9H, -SnMe.3, 2 J S n - H = 54 Hz) , 1.34-1.49 (m, 4H), 1.85 (quintet, 2H, J - 7.5 Hz), 2.34 (t, 2H, a l l y l i c protons, J •= 7.5 Hz), 3.40 (t, 2H, BrCH 2 - , J - 7.5 Hz), 3.70 (s, 3H, -OMe); 1 3 C nmr (75.6 MHz, CDCI3) 6: -6.8 (q, ^sn.c - 3 4 2 Hz), -6.7 (q, ^sn-C - 326 Hz), 27.8 ( t ) , 29.1 (t, 3 J S n - C " 8 Hz), 32.5 (t) , 33.6 (t) , 40.6 (t, 2 J S n - C -54 Hz, 3 J S n . c - 66 Hz), 51.0 (q), 149.2 (s), 164.8 (s), 172.1 (s). 1 1 9 S n nmr (111.8 MHz, CDCI3) *: -36.05 (s, J S n . S n - 330 Hz), -36.95 (s, J S n . S n - 330 Hz). Exact Mass calcd. for C ^ H ^ O ^ B r S ^ (M+-CH3): 546.9317; found: 546.9321. - 212 -Following general procedure 3, the ester (141) (120 mg, 0.21 mmol) was converted into the bis(trimethylstannyl) ester (158), after s t i r r i n g at 86°C for 21 h. Flash column chromatography of the pale yellow o i l on s i l i c a gel (10 g, elution with petroleum ether-diethyl ether; 9:1) followed by d i s t i l l a t i o n (air-bath temperature 1 3 0 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 106 mg (88%) of the (E) isomer (158). This colorless o i l exhibited i r (film): 1691, 1230, 772 cm"1; lE nmr (400 MHz, CDC13) 6: 0.15 (s, 9H, -SnMe3, 2 J S n . H - 5 6 H z ) . ° - 2 5 ( s . 9 H --SnMe3, 2 J _ S n _ H - 5 4 H z ) . ! - 3 2 (quintet, 2H, J - 7 Hz), 1.49 (quintet, 2H, J - 7 Hz), 1.88 (quintet, 2H, J - 7 Hz), 2.48 (t, 2H, a l l y l i c protons, J - 7 Hz), 3.41 (t, 2H, BrCH 2 - , J = 7 Hz), 3.70 (s, 3H, -OMe); 1 3 C nmr (75.6 MHz, CDC13) 6: -6.5 (q, ^Sn-C - 3 4 3 H z > > " 6 - ° (<1. ^Sn-C - 342 Hz), 28.2 (t) , 29.6 (t, 3 J S n - c - 7.6 Hz), 32.6 (t) , 33.5 (t) , 41.4 (t. 2^Sn-C " 54 Hz - 3 I S n -c)> 51.8 (q), 144.1 (s), 172.1 (s), 183.9 (s); 1 1 9 S n nmr (111.8 MHz, CDC13) 6: -50.47 (s, J S n - S n " 558 Hz), -51.49 (s, J S n . S n - 558 Hz). Exact Mass calcd. for C ^ ^ g C ^ ^ r S ^ (M + -CH 3 ): 546.9317; found: 546.9321. Preparation of methyl (Z)-2.3-bis(trimethylstannyl)-8-iodo-2-octenoate  (142) Following general procedure 2, to a s t i rred solution of methyl - 213 -8-iodo-2-octynoate (99) (1.071 g, 3.825 mmol) in 60 mL of THF was added hexamethylditin (3.825 mmol) and (PPh 3) 4Pd (55 mg, 0.048 mmol). The mixture was s t i rred at reflux for 6 h. Concentration, followed by column chromatography of the resultant black o i l on s i l i c a gel (40 g, elution with petroleum ether-diethyl ether; 97:3) and subjection of each of the two o i l s thus obtained to vacuum (0.05 Torr; 2 h) , afforded 1.54 g (76%) of the (Z) isomer (142) and 139 mg of methyl 8-iodo-2-octynoate (99). The colorless o i l (142) exhibited i r (film): 1707, 1191, 770 cm"1; -^H nmr (400 MHz, CDC13) 6: 0.23 (s, 9H, -SnMe.3, 2 J S n - H " 5 3 H z > > 0.24 (s, 9H, -SnMe3, 2 J S n _ H - 5 5 H z ) . 1.32-1.45 (m, 4H), 1.82 (quintet, 2H, ICH 2 CH 2 - , J - 7 Hz), 2.30-2.37 (m, 2H, I ( C H 2 ) 4 C H 2 - ) , 3.18 (t, 2H, I C H 2 - , J » 7 Hz), 3.69 (s, 3H, -OMe). Exact Mass calcd. for C 1 4 H 2 8 O 2 I 1 1 8 S n 1 2 0 S n (M+-CH3): 592.9174; found: 592.9170. Preparation of compound (165) C 0 2 E t < SnMe 2 C 0 2 E t To a s t i rred solution of diethyl 2,7-nonadiyndioate (112) (28 mg, 0.1186 mmol) in 5 mL of dry THF was added hexamethylditin (0.1186 mmol) and (PPh3)4Pd (5 mg, 0.004 mmol). The mixture was s t i rred at reflux for 9 h. Concentration, followed by flash column chromatography of the crude o i l on s i l i c a gel (5 g, elution with petroleum ether-diethyl - 214 -ether; 9:1) and d i s t i l l a t i o n (air-bath temperature 115°C /0 .05 Torr) of the o i l thus obtained afforded 26 mg (56%) of the diene (165). This colorless o i l exhibited i r (film): 1698, 1611, 1216 (br), 1100, 771 cm"1; X H nmr (400 MHz, C D C 1 3 ) 8: 0.51 (s, 6H, -SnMe2. 2Isn-H ~ 6 0 Hz>> 1.28 (t, 6H , -OCH2CH3, J - 7 Hz), 2 .02 (quintet, 2H, methylene protons, J - 8 Hz), 2.87 (t, 4 H , a l l y l i c protons, J - 8 Hz), 4.17 (q, 4 H , - 0 C H 2 C H 3 , J - 7 Hz); 1 3 C nmr (75.6 MHz, CDCI3) 8: -7.8 (q), 14.4 (q), 25.7 ( t ) , 32.0 (t, 3 J S n . c - 46 Hz), 60.1 ( t ) , 129.7 (s), 169.5 (s), 172.8 (s). Exact Mass calcd. for C 1 5 H 2 2 0 4 S n (M+-CH3): 386.0540; found: 386.0530. General Procedure 4 : Preparation of (E)-N.N-dimethvl-2 .3-bis(tri- methylstannyl) -2-alkenamides (170) Me 3Sn CONMe2 To a s t i rred solution of the appropriate acetylenic amide (1 equiv) in dry THF was added hexamethylditin (1 equiv), followed by Pd(PPh3)4 (0.0095-0.016 equiv). The reaction mixture was s t i rred at room tempera-ture or under reflux for 26-72 h. Concentration of the mixture, followed by column chromatography of the resultant crude o i l on s i l i c a gel , afforded in one case (Me-C»C-CONMe2) a mixture of the (Z) and (E) isomers, and in a l l other cases studied, gave exclusively the (E) isomer (170). The (Z) isomer (167) was subjected to a vacuum of 0.05 Torr for - 215 -1 h at room temperature and the (E) isomers were d i s t i l l e d (receiving bulb cooled to - 1 0 ° C ) , affording in a l l cases clear o i l s . Preparation of (Z)- and (E)-N.N-dimethvl-2.3-bis(trimethylstannyl)-2- butenamides (167) and (168) Me3Sn SnMe3 Me3Sn CONMe2 W H Me CONMe2 Me SnMe3 167 168 Following general procedure 4, to a s t irred solution of N,N-di-methyl-2-butynamide (166) (269 mg, 2.43 mmol) in 20 mL of dry THF was added hexamethylditin (2.43 mmol) and (PPt^^Pd (27 mg, 0.023 mmol). The mixture was s t irred at room temperature for 44 h. Concentration, followed by flash column chromatography of the resultant crude o i l on s i l i c a gel (25 g, elution with petroleum ether-ethyl acetate; 1:1) afforded two o i l s , A and B. D i s t i l l a t i o n (air-bath temperature 1 0 5 ° C / 0 . 1 Torr) of the o i l B provided 140 mg (13%) of (E)-N,N-dimethyl-2,3-bis(trimethylstannyl)-2-butenamide (168), while subjection of the o i l A to vacuum (0.1 Torr; 1.5 h) afforded 540 mg (50%) of (Z)-N,N-dimethyl-2,3-bis(trimethylstannyl)-2-butenamide (167). The colorless o i l (167) exhibited i r (film): 1620, 1390, 1160, 770 cm"1; X H nmr (270 MHz, CDC13) 6: 0.20 (s, 9H, -SnMe.3, 2 J S n . H - 54 Hz), 0.22 (s, 9H, -SnMe.3, 2 J S n _ H - 54 Hz), 1.94 (s, 3H, v iny l methyl, 3 J S n . H - 45 Hz, 4 j -Sn-H ~ 1 1 Hz>> 2 - 9 1 < s' 3 H - -NMe)' 2 9 5 (s. 3 H , -NMe). Exact Mass calcd. for C 1 1 H 2 40NSn 2 (M+-CH3): 425.9902; found: 425.9909. - 216 -The colorless o i l (168) exhibited i r (film): 1620, 1390, 1170, 775 c m - 1 ; X H nmr (80 MHz, CDC13) 6: 0.12 (s, 9H, -SnMe.3, 2 j-Sn-H " 5 3 Hz>> 0.25 (s, 9H, -SnMe.3, 2 J S n . H - 53 Hz), 2.05 (s, 3H, v iny l methyl, 3 J S n - H - 46 Hz, 4J_sn-H " 1 1 H z ) » 2 - 9 2 (s> 6 H> -NMe 2). Exact Mass calcd. for c l l H 2 4 O N S n 2 (M+-CH3): 425.9902; found: 425.9906. Preparation of (E)-N.N-dimethyl-2.3-bis(trimethylstannyl)-2-pentenamide Following general procedure 4, to a s t irred solution of N,N-dimethyl-2-pentynamide (171) (565 mg, 4.42 mmol) in 70 mL of dry THF was added hexamethylditin (4.52 mmol) and (PPh 3) 4Pd (50 mg, 0.045 mmol). The mixture was s t i rred at reflux for 72 h. Concentration, followed by column chromatography of the resultant black o i l on s i l i c a gel (30 g, elution with petroleum ether-diethyl ether; 1:1) and d i s t i l l a t i o n (air-bath temperature 1 0 5 - 1 0 8 ° C / 0 . 1 Torr) of the o i l thus obtained, afforded 960 mg (48%) of the amide (174). This colorless o i l exhibited i r (fi lm): 1620, 1385, 1160, 775 cm"1; i H nmr (80 MHz, CDC13) 6: 0.15 (s, 9H, -SnMe.3, 2 j-Sn-H " 5 3 H z ) . 0 2 5 < s» 9 H - -SnMe.3, 2 j-Sn-H " 5 4 H z > > 1.00 (t, 3H, -CH 2 CH 3 , J - 7 Hz), 2.32 (q, 2H, -CH 2 CH 3 , J - 7 Hz), 2.92 (s, 6H, -NMe 2); 1 3 C nmr (75.4 MHz, CDCI3) 6: -8.01 (q, ^sn-c " 3 1 9 Hz>. -7.56 (q, ^ s n . c - 327 Hz), 14.6 (q, 3 J S n - C - 8 Hz), 34.0 (q), 36.0 (t, 2 j-Sn-C = 65 Hz - 3 J S n - c ) . 3 8 - ° (q). 1 5 1 - 4 ( s ) . 1 62.0 (s), 173.4 (s); (174) Me3Sn CONMe2 Et SnMe3 - 217 -i i y S n nmr (111.8 MHz, CDC13) 6: -47.8 (s, J S n . S n = 6 4 4 H z ) . -50.5 (s, J-Sn-Sn ™ 6 4 4 H z ) - Exact Mass calcd. for C 1 2 H 2 6 O N S n 2 ( M 4 " - ^ ) : 440.0058; found: 440.0052. Preparation of (E)-N.N-dimethyl-2.3-bis(trimethylstannyl)-6-bromo-2- hexenamide (175) Following general procedure 4, to a s t irred solution of N,N-dimethyl-6-bromo-2-hexynamide (172) (359 mg, 1.647 mmol) in 25 mL of dry THF was added hexamethylditin (1.647 mmol) and (PPl^^Pd (30 mg, 0.026 mmol). The mixture was s t i rred at reflux for 26 h. Concentration, followed by column chromatography of the resultant brown o i l on s i l i c a gel (20 g, elution with petroleum ether-ethyl acetate; 1:1) and d i s t i l l a t i o n (air-bath temperature 1 2 5 ° C / 0 . 1 Torr) of the o i l thus obtained, afforded 679 mg (75%) of the amide (175). This yellow o i l exhibited i r (film): 1619, 1491, 1162, 769 cm"1; X H nmr (400 MHz, CDCI3) 5: 0.16 (s, 9H, -SnMe.3, 2 j -Sn-H " 5 3 H z > • ° - 2 6 <s> 9 H> -SnMe.3, 2 j-Sn-H " 55 Hz), 1.91 (quintet, 2H, BrCH 2 CH 2 CH 2 - , J - 7.5 Hz), 2.39-2.52 (m, 2H, BrCH 2 CH 2 CH 2 - ) , 2.91 (s, 6H, -NMe 2), 3-42 (t, 2H, BrCH 2 CH 2 CH 2 - , J - 7.5 Hz). Exact Mass calcd. for C 1 3 H 2 70N 8 1 BrSn 2 (M" 1"-^): 533.9300; found: 533.9304. B r - 218 -Preparation of (E)-N.N-dimethyl-2.3-bis(trimethylstannyl)-6-tert-butyl- dimethylsiloxy-2-hexenamide (176) Following general procedure 4, to a s t i rred solution of N,N-di-methyl-6-tert-butyldimethylsiloxy-2-hexynamide (173) (159 mg, 0.59 mmol) in 20 mL of dry THF was added hexamethylditin (0.59 mmol) and (PPl^^Pd (10 mg, 0.008 mmol). The mixture was s t irred at reflux for 48 h. Concentration, followed by column chromatography of the resultant crude o i l on s i l i c a gel (20 g, elution with petroleum ether-ethyl acetate; 4:1) and d i s t i l l a t i o n (air-bath temperature 1 7 0 ° C / 0 . 1 Torr) of the o i l thus obtained, afforded 222 mg (63%) of the amide (176). This colorless o i l exhibited i r (film): 1620, 1380, 1100, 840, 780 cm' 1 ; -^H nmr (400 MHz, CDC13) 8: 0.06 (s, 6H, ButMe^SiO-), 0.16 (s, 9H, -SnMe.3, 2^Sn-H = 54 Hz), 0.25 (s, 9H, -SnMe.3, 2^Sn-H = 5 4 H z > • 0 9 1 <s> 9 H - £ 1 1 ^ 6 2 8 1 0 - ) , 1.57 (quintet, 2H, Bu tMe 2Si0CH 2CH 2CH2-, J = 6 .0Hz) , 2.33-2.42 (m, 2H, Bu tMe2SiOCH2CH2CH2-), 2.92 (s, 3H, -NMe), 2.94 (s, 3H, -NMe), 3.64 (t, 2H, Bu tMe2SiOCH2CH2CH2-, J - 6.0 Hz); 1 3 C nmr (75.4 MHz, CDCI3) 6: -8.0 (^ISn-C - 3 2 7 H z )> ' 7 - 6 <<1. ^iSn-C " 3 2 8 H z > • ' 5 - 7 • 1 8 • 3 <s> • 2 5 - 9 (q), 33.5 (t) , 34.2 (q), 38.3 (q), 40.3 (t, 3 J S n . C - 63 Hz - 2 i S n-c)• 63.0 (t) , 152.5 (s), 160.5 (s), 173.7 (s). Exact Mass calcd. for c 1 9 H 4 2 ° 2 N S i S n 2 (M + -CH 3 ): 584.1029; found: 584.1031. Me3Sn CONMe 2 t Bu Me2SiO - 219 -V. Chemistry of a lky l (Z)- and (E)-2,3-bis(trimethylstannyl)-2-alkenoates General Procedure 5: Transmetalation of alkvl (Z)- and (E) - 2 . 3 - b i s ( t r i - methylstannyl') -2-alkenoates and reaction of the resultant intermediates  with electrophiles To a cold ( - 9 8 ° C ) , s t irred solution of the appropriate a lky l (Z)- or (E)-2,3-bis(trimethylstannyl)-2-alkenoate (1 equiv) in anhydrous THF (-20 mL per mmol) was added methyllithium (1.1-1.2 equiv) as a solution in ether. The resulting dark yellow solution was s t i rred at -98°C for 10-35 min. The appropriate electrophile (3-20 equiv) which had been passed through basic alumina, was added and the mixture was s t irred at -98°C for 30 min and at -78°C for 45 min-2.5 h. Saturated aqueous ammonium chloride (2 mL/mmol) and ether (20 mL/mmol) were added and the mixture was allowed to warm to room temperature. The organic layer was washed three times with saturated aqueous ammonium chloride dried over anhydrous magnesium sulfate, and concentrated. The resulting o i l was either d i s t i l l e d d irect ly or was flash chromatographed on s i l i c a gel (elution with petroleum ether-diethyl ether or petroleum ether-dichloro-methane) prior to d i s t i l l a t i o n . - 220 -Preparation of ethvl (Z)-2-(3-chloropropyl)-3-trimethylstannvl-2- butenoate (180) Following general procedure 5, to a cold ( - 9 8 ° C ) , s t i rred solution of ethyl (E)-2,3-bis(trimethylstannyl)-2-butenoate (77) (288 mg, 0.515 mmol) in 6 mL of dry THF was added a solution of methyllithium (0.593 mmol) in ether. After the mixture had been s t irred at -98°C for 10 min, l-chloro-3-iodopropane (-20 mmol) was added and the solution was s t irred at -98°C for 30 min and at -78°C for 1.5 h. Normal workup, followed by flash column chromatography of the residual o i l on s i l i c a gel (15 g, elution with petroleum ether-diethyl ether; 17:1) and d i s t i l l a t i o n (air-bath temperature, 8 5 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 98 mg (54%) of the chloride (180) (the s t i l l pot contained some polymeric gum). This colorless o i l exhibited i r (film): 1693, 1263, 774 cm- 1 ; i H nmr (400 MHz, CDC13) 6: 0.13 (s, 9H, -SnMe3, "SIsn-H " 5 5 H z > • 1.31 (t, 3H, -OCH 2CH 3 , J - 7 Hz), 1.89 (quintet, 2H, C1CH 2CH 2CH 2-, J = 8 Hz), 2.10 (s, 3H, v iny l methyl, 3 J S n - H " 5 1 H z >• 2 • 6 0 ( C ' 2 H> C1CH 2 CH 2 CH 2 - , J - 8 Hz), 3.53 (t, 2H, C1CH 2CH 2CH 2-, J - 8 Hz), 4.21 (q, 2H, -0CH 2 CH 3 , J - 7 Hz); 1 3 C nmr (75.6 MHz, CDC13) 6: -6.7 (q, ^Sn-C " 359 Hz), 14.2 (q), 22.0 (q, 2 J S n . C " 4 4 H z >- 2 5 - 2 ( 3^Sn-C " 4 1 H z >• 3 2 - 2 ( t ) , 44.8 ( t ) , 60.9 (t) , 137.6 (s), 164.5 (s), 168.9 (s). Exact Mass calcd. for C 1 1 H 2 0 O 2 3 5 C l S n (M+'C^): 339.0174; found: 339.0167. Cl - 221 -Preparation of ethyl (E)-2-trimethvlsilvl-3-trimethylstannvl-2-butenbate Following general procedure 5, to a cold ( - 9 8 ° C ) , s t i rred solution of ethyl (E)-2,3-bis(trimethylstannyl)-2-butenoate (77) (178 mg, 0.402 mmol) in 6 mL of dry THF was added a solution of methyllithium (0.433 mmol) in ether. After the mixture had been s t irred at -98°C for 10 min, chlorotrimethylsilane (-10 mmol) was added and the solution was s t irred at -98°C for 30 min and at -78°C for 2 h. Normal workup, followed by d i s t i l l a t i o n (air-bath temperature 8 0 ° C / 0 . 0 5 Torr) of the residual o i l afforded 99 mg (70%) of the stannyl silane (181). This colorless o i l exhibited i r (film): 1695, 1240, 850, 775 c m - 1 ; ^ nmr (80 MHz, CDC13) 5: 0.15 (s, 9H, -SnMe3, 2 J S n - H ~ 5 3 Hz>> ° - 2 5 <s> 9 H - -SiMe 3 ) , 1.30 (t, 3H, -OCH 2 CH 3 , J - 7 Hz), 2.22 (s, 3H, v inyl methyl, 3J_sn-H ~ 5 1 H z > > 4.12 (q, 2H, -OCH 2CH 3 , J - 7 Hz). Exact Mass calcd. for C n H 2 3 0 2 S i S n (M + -CH 3 ) : 335.0489; found: 335.0487. Preparation of ethvl (Z)-2-(2-methyl-2-propenvl)-3-trimethvlstannvl-2- butenoate (182) (181) Me3Sn C0 2 E t Me SiMe 3 - 222 -Following general procedure 5, to a cold ( - 9 8 ° C ) , s t irred solution of ethyl (E)-2,3-bis(trimethylstannyl)-2-butenoate (77) (112 mg, 0.254 mmol) in 5 mL of dry THF was added a solution of methyllithium (0.319 mmol) in ether. After the mixture had been s t irred at -98°C for 10 min, 3-iodo-2-methylpropene (-5 mmol) was added and the solution was s t irred at -98°C for 30 min and at -78°C for 2 h. Normal workup, followed by flash column chromatography of the residual o i l on s i l i c a gel (10 g, elution with petroleum ether-dichloromethane; 44:1) and d i s t i l l a t i o n (air-bath temperature ~ 8 0 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 58 mg (69%) of the alkene (182). This colorless o i l exhibited i r (fi lm): 1680, 1580, 1280, 770 cm"1; X H nmr (80 MHz, CDC13) 6: 0.11 (s, 9H, -SnMe.3, 2 I S n - H " 5 4 Hz>> 1 - 2 3 3 H> -OCH 2CH 3 , J - 7 Hz), 1.62 (s, 3H, v iny l methyl), 2.01 (s, 3H, v iny l methyl, 3 J_s n -H " 4 8 H z > » 3.03-3.18 (br s, 2H, b i s - a l l y l i c protons), 4.13 (q, 2H, -0CH 2CH 3 , J = 7 Hz), 4.41-4.56 (br s, IH, v iny l proton), 4.58-4.65 (br s, IH, v inyl proton). Exact Mass calcd. for C 1 2 H 2 1 0 2 S n (M + -CH 3 ): 317.0564; found: 317.0559. Preparation of ethyl (Z)-2-(4-iodo-4-pentenyl)-3-trimethylstannyl-2- butenoate (183) - 223 -Following general procedure 5, to a cold ( - 9 8 ° C ) , s t irred solution of ethyl (E)-2,3-bis(trimethylstannyl)-2-butenoate (77) (92 mg, 0.209 mmol) in 5 mL of dry THF was added a solution of methyllithium (0.262 mmol) in ether. After the mixture had been s t irred at -98°C for 30 min, 2,5-diiodo-l-pentene (-40 mmol) was added and the solution was s t irred at -98°C for 30 min and at -78°C for 2.5 h. Normal workup, followed by flash column chromatography of the residual o i l on s i l i c a gel (10 g, elution with petroleum ether-diethyl ether; 97:3) and d i s t i l l a t i o n (air-bath temperature 1 2 0 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 41 mg (42%) of the alkene (183). This colorless o i l exhibited i r (fi lm): 1695, 1220, 775 cm"1; X H nmr (270 MHz, CDC13) 5: 0.13 (s, 9H, -SnMe3, 2 J S n . H = 54 Hz), 1.31 (t, 3H, -OCH 2CH 3 , J - 7 Hz), 1.75 (quintet, 2H, -CH 2 CH 2 CH 2 CICH 2 , J - 8 Hz), 2.07 (s, 3H, v iny l methyl, 3 j-Sn-H = 5 2 H z > ' 2 - 4 2 ( c ' 4 H> -CH 2CH 2CH 2CICH 2 , J = 8 Hz), 4.19 (q, 2H, -OCH 2 CH 3 , J - 7 Hz), 5.66 (IH, v iny l proton, J - 1.5 Hz), 6.04 (IH, v iny l proton, J •= 1.5 Hz). Exact Mass calcd. for C 1 3 H 2 2 0 2 I S n (M + -CH 3 ): 456.9689; found: 456.9685. Preparation of ethyl (Z)-2-(3-methyl-2-butenvl)-3-trimethylstannyl-2- butenoate (184) - 224 -Following general procedure 5, to a cold ( - 9 8 ° C ) , s t irred solution of ethyl (E)-2,3-bis(trimethylstannyl)-2-butenoate (77) (112 mg, 0.254 mmol) in 5 mL of dry THF was added a solution of methyllithium (0.317 mmol) in ether. After the mixture had been s t irred at -98°C for 30 min, freshly d i s t i l l e d 1-bromo-3-methyl-2-butene (-5 mmol) was added and the solution was s t i rred at -98°C for 30 min and at -78°C for 3 h. Normal workup, followed by d i s t i l l a t i o n (air-bath temperature 8 0 ° C / 0 . 0 5 Torr) of the residual o i l afforded 58 mg (66%) of the alkene (184). This colorless o i l exhibited i r (film): 1680, 1580, 1270, 770 cm"1; lE nmr (400 MHz, CDC13) 8: 0.13 (s, 9H, -SnMe3, 2 J S n - H " 5 5 H z > > 1 - 3 0 (-t> 3 H> -0CH 2 CH 3 , J - 7 Hz), 1.69 (s, 3H, v iny l methyl), 1.71 (s, 3H, v iny l methyl), 2.08 (s, 3H, v iny l methyl, 3J_s n-H " 5 1 H z > • 3 - 1 4 ( d- 2 H> b i s - a l l y l i c protons, J - 7.5 Hz), 4.19 (q, 2H, -OCH 2CH 3 , J - 7 Hz), 5.00 (t, IH, v iny l proton, J = 7.5 Hz). Exact Mass calcd. for C^ 3 H 2 3 0 2 Sn (M + -CH 3 ) : 331.0720; found: 331.0724. Preparation of ethvl (Z)-2-(3-trimethvlsilvl-2-propvnyl)-3-trimethyl- stannyl -2-butenoate (185) Following general procedure 5, to a cold ( - 9 8 ° C ) , s t irred solution of ethyl (E)-2,3-bis(trimethylstannyl)-2-butenoate (77) (88 mg, 0.200 mmol) in 5 mL of dry THF was added a solution of methyllithium (0.25 - 225 -mmol) in ether. After the mixture had been s t irred at -98°C for 30 min, 3-bromo-l-trimethylsilylpropyne (-4.0 mmol) was added and the solution was s t i rred at -98°C for 30 min and at -78°C for 2.5 h. Normal workup, followed by column chromatography of the residual o i l on s i l i c a gel (5 g, elution with petroleum ether-dichloromethane; 97:3) and d i s t i l l a t i o n (air-bath temperature 1 0 5 ° C / 0 . 5 Torr) of the o i l thus obtained, afforded 30 mg (40%) of the trimethylsilylalkyne (185). This colorless o i l exhibited i r (fi lm): 2160, 1685, 1270, 840, 765 c m - 1 ; X H nmr (400 MHz, CDC13) 5: 0.14 (s, 9H, -SiMe 3 ) , 0.15 (s, 9H, -SnMe.3, 2 J S n - H ~ 5 5 H z ) • 1.31 (t, 3H, -OCH 2CH 3 , J - 7 Hz), 2.14 (s, 3H, v inyl methyl, 3 J S n - H " 5 0 Hz), 3.36 (s, 2H, a l l y l i c protons), 4.14 (q, 2H, -OCH 2CH 3 , J = 7 Hz). Exact Mass calcd. for C 1 4 H 2 5 0 2 S i S n (M+-CH3): 373.0640; found: 373.0643. Preparation of methyl (Z)-2-methyl-3-trimethvlstannvl-5-(2-cvclo- pentenvl)-2-pentenoate (186) Following general procedure 5, to a cold ( - 9 8 ° C ) , s t i rred solution of methyl (E)-2,3-bis(trimethylstannyl)-5-(2-cyclopentenyl)-2-pentenoate (153) (75.7 mg, 0.149 mmol) in 5 mL of dry THF was added a solution of methyllithium (0.178 mmo 1) in ether. After the mixture had been s t i rred at -98°C for 15 min, iodomethane (-3.0 mmol) was added and the solution - 226 -was s t i rred at -98°C for 30 min and at -78°C for 1 h. Normal workup, followed by column chromatography of the residual o i l on s i l i c a gel (10 g, elution with petroleum ether-diethyl ether; 99:1) and d i s t i l l a t i o n (air-bath temperature 100°C/0 .5 Torr) of the o i l thus obtained, afforded 39 mg (72%) of the ester (186). This colorless o i l exhibited i r (film): 1697, 1280, 770 cm"1; 1 H nmr (400 MHz, CDCI3) 6: 0.13 (s, 9H, -SnMe3, 2 j-Sn-H - 5 5 H z > . 1-17-1.38 (m, 2H), 1.41-1.51 (m, IH) , 1.94 (s, 3H, v i n y l methyl, 4 J S n - H - 9 Hz), 2.02-2.12 (m, IH), 2.23-2.42 (m, 2H), 2.46 (t, 2H, a l l y l i c protons, J = 7 Hz), 2.62-2.73 (m, IH), 3.74 (s, 3H, -OMe). 5.64-5.78 (m, 2H, v iny l protons). Exact Mass calcd. for c 1 4 H 2 3 ° 2 S n (M + -CH 3 ): 343.0720; found: 343.0723. Preparation of methvl (Z)-2-(2-methvl-2-propenyl)-3-trimethvlstannvl- 5-(2-cvclopentenyl)-2-pentenoate (187) Following general procedure 5, to a cold ( - 9 8 ° C ) , s t i rred solution of methyl (E)-2,3-bis(trimethylstannyl)-5-(2-cyclopentenyl)-2-pentenoate (153) (140 mg, 0.275 mmol) in 5 mL of dry THF was added a solution of methyllithium (0.330 mmol) in ether. After the mixture had been s t i rred at -98°C for 15 min, 3-iodo-2-methylpropene (-30 mmol) was added and the solution was s t i rred at -98°C for 35 min and at -78°C for 1.5 h. Normal Me 3 Sn C0 2 M e - 227 -workup, followed by d i s t i l l a t i o n (air-bath temperature 1 2 5 ° C / 0 . 0 5 Torr) of the residual o i l afforded 75 mg (68%) of the alkene (187). This colorless o i l exhibited i r (film): 1700, 1290, 1210, 780 c m - 1 ; X H nmr (400 MHz, CDC13) 6: 0.14 (s, 9H, -SnMe3, 2 J S n - H ° 5 4 H z)> 1-17-1.49 (m, 3H), 1.76 (s, 3H, v iny l methyl), 2.00-2.10 (m, IH), 2.21-2.45 (m, 4H), 2.61-2.71 (m, IH), 3.11 (s, 2H, b i s - a l l y l i c protons), 3.70 (s, 3H, -OMe), 4.53 (s, IH, v inyl proton), 4.71 (s, IH, v iny l proton), 5.64-5.77 (m, 2H, v iny l protons). Exact Mass calcd. for C 1 7H270 2Sn (M + -CH 3 ): 383.1033; found: 383.1030. Preparation of methyl (Z)-2-(3-methyl-2-butenvl)- 3-trimethylstannyl- 5-(2-cvclopentenyl)-2-pentenoate (188) Following general procedure 5, to a cold ( - 9 8 ° C ) , s t i rred solution of methyl (E)-2,3-bis(trimethylstannyl)-5-(2-cyclopentenyl)-2-pentenoate (153) (151 mg, 0.297 mmol) in 6 mL of dry THF was added a solution of methyllithium (0.348 mmol) in ether. After the mixture had been s t i rred at -98°C for 10 min, freshly d i s t i l l e d 1-bromo-3-methyl-2-butene (-5.0 mmol) was added and the solution was s t irred at -98°C for 30 min and at -78°C for 1.5 h. Normal workup, followed by d i s t i l l a t i o n (air-bath temperature 1 1 5 - 1 2 0 ° C / 0 . 0 5 Torr) of the residual o i l afforded 87 mg - 228 -(71%) of the alkene (188). This colorless o i l exhibited i r (film): 1698, 1580, 1285, 1230, 775 cm"1; XH nmr (AOO MHz, CDC13) 6: 0.13 (s, 9H, -SnMe.3, 2 J S n . H - 55 Hz), 1.17-1.40 (m, 2H), 1.40-1.51 (m, IH), 1.59 (s, 3H, vinyl methyl), 1.61 (s, 3H, vinyl methyl), 2.01-2.12 (m, IH), 2.22-2.57 (m, 4H), 2.64-2.74 (m, IH), 3.11 (d, 2H, bis-allylic protons, J - 7 Hz), 3.73 (s, 3H, -OMe), 4.99 (broad t, IH, vinyl proton, J - 7 Hz), 5.66-5.78 (m, 2H, vinyl protons). Exact Mass calcd. for C^g^^Sn (M+-CH3): 397.1190; found: 397.1188. Preparation of ethyl (Z)-2-(2-methvl-2-propenvl)-3-trimethylstannyl-4- tert-butyldimethylsiloxy-2-butenoate (189) Following general procedure 5, to a cold (-98°C), stirred solution of ethyl (E)-2,3-bis(trimethylstannyl)-4-tert-butyldimethylsiloxy-2-butenoate (152) (386 mg, 0.675 mmol) in 15 mL of dry THF was added a solution of methyllithium (0.843 mmol) in ether. After the mixture had been stirred at -98°C for 25 min, 3-iodo-2-methylpropene (-7 mmol) was added and the solution was stirred at -98°C for 30 min and at -78°C for 1.5 h. Normal workup, followed by distillation (air-bath temperature 135oC/0.1 Torr) of the residual o i l afforded 240 mg (74%) of the alkene (189). This colorless o i l exhibited i r (film): 1700, 1645, 1270, 1050, 845, 780 cm"1; XH nmr (400 MHz, CDCI3) S: 0.04 (s, 6H, B^M^Si-), 0.16 - 229 -(s, 9H, -SnMe3, 2 J S n . H - 55 Hz), 0.89 (s, 9H, B i ^ M e ^ i - ) , 1.27 (t, 3H, -OCH 2CH 3 , J - 7 Hz), 1.74 (s, 3H, v iny l methyl), 3.10 (s, 2H, b i s - a l l y l i c protons), 4.17 (q, 2H, -OCH 2CH 3 , J - 7 Hz), 4.38 (s, 2H, -CH 2OSiBu tMe 2 , 3J_Sn-H " 4 8 H z > • 4 - 5 6 (s, IH, v iny l proton), 4.73 (s, IH, v iny l proton) . Exact Mass calcd. for C l g H 3 5 0 3 S i S n (M+-CH;}): 447.1378; found: 447.1379. Preparation of ethvl (Z)-2-methyl-3-trimethvlstannvl-4-tert-butvl- dimethylsiloxv-2-butenoate (190) Following general procedure 5, to a cold ( - 9 8 ° C ) , s t i rred solution of ethyl (E)-2.3-bis(trimethylstannyl)-4-tert-butvldimethvlsiloxv 2-butenoate (152) (93 mg, 0.1625 mmol) in 5 mL of dry THF was added a solution of methyllithium (0.1788 mmol) in ether. After the mixture had been s t irred at -98°C for 15 min, iodomethane (-20 mmol) was added and the solution was s t i rred at -98°C for 30 min and at -78"C for 1.5 h. Normal workup, followed by d i s t i l l a t i o n (air-bath temperature 9 5 - 1 0 0 ° C / 0.1 Torr) of the residual o i l afforded 51 mg (74%) of the alkene (190). This colorless o i l exhibited i r (film): 1698, 1640, 1270, 1050, 840, 770 cm"1; ltt nmr (270 MHz, CDC13) 6: 0.04 (s, 6H, B^Me^Si-) , 0.13 (s, 9H, -SnMe3, 2 J S n - H ~ 5 6 Hz>> ° - 8 8 < s» 9 H> Bu t Me 2 Si- ) , 1.28 (t, 3H, -OCH 2CH 3 , J - 7 Hz), 1.94 (s, 3H, v iny l methyl), 4.17 (q, 2H, -OCH 2CH 3 , J - 7 Hz), - 230 -4.41 (s, 2H, a l l y l i c protons, ^Isn-H " 4 8 H z >: c n m r < 7 5 - 6 m z > CDC13) 5: -6.0 (q, ^ s n . c - 365 Hz), -5.2 (q), 14.3 (q), 14.6 (q), 18.3 (s), 26.0 (q), 61.0 (t) , 64.3 (t, 2 J S n - C " 2 7 H z > . 1 3 4 - 5 <s) > i 6 3 - 1 <s) > 169.5 (s). Exact Mass calcd. for C 1 5 H 3 1 0 3 S i S n (M+-CH3): 407.1065; found: 407.1062. Preparation of ethyl (Z)-2-(3-methyl-2-butenyl)-3-trimethylstannyl- 4-tert-butyldimethylsiloxy-2-butenoate (191) Following general procedure 5, to a cold ( - 9 8 ° C ) , s t i rred solution of ethyl (E)-2,3-bis(trimethylstannyl)-4-tert-butyldimethylsiloxy-2-bute-noate (152) (813 mg, 1.421 mmol) in 40 mL of dry THF was added a solution of methyllithium (1.70 mmol) in ether. After the mixture had been s t i rred at -98°C for 25 min, freshly d i s t i l l e d l-bromo-3-methyl-2-butene (-5.0 mmol) was added and the solution was s t i rred at -98°C for 30 min and at -78°C for 1.5 h. Normal workup, followed by d i s t i l l a t i o n (air-bath temperature 1 1 0 ° C / 0 . 1 Torr) of the residual o i l afforded 546 mg (81%) of the alkene (191). This colorless o i l exhibited i r (film): 1698, 1640, 1280, 1080, 840, 780 cm"1; X H nmr (400 MHz, CDC13) 5: 0.05 (s, 6H, B^Me^Si-) , 0.15 (s, 9H, -SnMe3, 2 J S n - H " 5 6 H z ) • ° - 9 0 <s> 9 H> Bu t Me 2 Si - ) , 1.27 (t, 3H, -OCH 2CH 3 , J - 7 Hz), 1.68 (s, 6H, v iny l Me 3 Sn C0 2Et BJ Me 2 SiO - 231 -methyls), 3.10 (d, 2H, b i s - a l l y l i c protons, J - 7 Hz), 4.19 (q, 2H, -OCH 2CH 3 , J - 7 Hz), 4.43 (s, 2H, -CH 2OSiBu tMe 2, 3J.Sn-H = 4 8 H z)> 4 - 9 7 (broad t, IH, v iny l proton, J - 7 Hz). Exact Mass calcd. for C 1 9 H 3 7 0 3 S i S n (M+'CH^: 461.1534; found: 461.1536. Preparation of methyl (Z)-2-methvl-3-trimethylstannyl-3-cvclopropvl-2- propenoate (192) Me3Sn C02Me Following general procedure 5, to a cold ( - 9 8 ° C ) , s t i rred solution of methyl (E)-2,3-bis(trimethylstannyl)-3-cyclopropyl-2-propenoate (149) (43.3 mg, 0.09 mmol) In 5 mL of dry THF was added a solution of methyl-lithium (0.140 mmol) in ether. After the mixture had been s t irred at -98°C for 15 min, iodomethane (-2 mmol) was added and the solution was s t i rred at -98°C for 30 min and at -78°C for 1.5 h. Normal workup, followed by d i s t i l l a t i o n (air-bath temperature 8 0 ° C / 0 . 1 Torr) of the residual o i l afforded 21.6 mg (79%) of the ester (192). This colorless o i l exhibited i r (film): 1695, 1270, 770 c m - 1 ; X H nmr (270 MHz, CDC13) 5: 0.13 (s, 9H, -SnMe3, 2 J S n _ H - 54 Hz), 0.32-0.41 (m, 2H), 0.83-0.94 (m, 2H), 1.44-1.54 (m, IH), 2.06 (s, 3H, v iny l methyl), 3.70 (s, 3H, -OMe). Exact Mass calcd. for C 1 0 H 1 7 O 2 S n (M+-CH5): 289.0250; found: 289.0240. - 232 -Preparation of methyl (Z)-2-(2-methyl-2-propenvl)-3-trimethvlstannvl- 3-cvclopropvl-2-propenoate (193) Following general procedure 5, to a cold ( - 9 8 ° C ) , s t i rred solution of methyl (E)-2,3-bis(trimethylstannyl)-3-cyclopropyl-2-propenoate (149) (354 mg, 0.779 mmol) in 8 mL of dry THF was added a solution of methyl-lithium (0.896 mmol) in ether. After the mixture had been s t i rred at -98°C for 10 min, 3-iodo-2-methylpropene (-7 mmol) was added and the solution was s t irred at -98"C for 30 min and at -78°C for 1.5 h. Normal workup, followed by d i s t i l l a t i o n (air-bath temperature 9 5 ° C / 0 . 1 Torr) of the residual o i l afforded 204 mg (76%) of the alkene (193). This colorless o i l exhibited i r (film): 1700, 1290, 1205, 780 cm _ 1 ; X H nmr (270 MHz, CDC13) 6: 0.15 (s, 9H, -SnMe.3, 2 J S n . H - 56 Hz), 0.40-0.48 (m, 2H), 0.80-0.90 (m, 2H), 1.46-1.58 (m, IH), 1.75 (s, 3H, v iny l methyl), 3.28 (s, 2H, b i s - a l l y l i c protons), 3.67 (s, 3H, -OMe), 4.46 (s, IH, v iny l proton), 4.68 (s, IH, v iny l proton). Exact Mass calcd. for c 1 3 H 2 1 ° 2 S n (M" 1"-^): 329.0564; found: 329.0566. - 233 -Preparation of methyl (Z)-2-(2-propenvl)-3-trimethylstannyl-2- pentenoate (179) Following general procedure 5, to a cold ( - 9 8 ° C ) , s t i rred solution of methyl (Z)-2,3-bis(trimethylstannyl)-2-pentenoate (125) (3.47 g, 8.46 mmol) in 120 mL of dry THF was added a solution of methyllithium (9.73 mmol) in ether. After the mixture had been s t irred at -98°C for 15 min, 3-iodopropene (12.69 mmol) was added and the solution was s t i rred at -98°C for 30 min and at -78°C for 45 min. Normal workup, followed by d i s t i l l a t i o n (air-bath temperature 8 2 - 8 6 ° C / 0 . 0 5 Torr) of the residual o i l afforded 2.295 g (85%) of the alkene (179). This colorless o i l exhibited i r (film): 3080, 1700, 1639, 1284, 1213, 773 cm"1; X H nmr (270 MHz, CDC13) 6: 0.15 (s, 9H, -SnMe.3, 2J.Sn-H = 5 4 H z ) > ° - 9 3 (t> 3 H ' -CH 2 CH 3 , J - 7.5 Hz), 2.45 (q, 2H, -CH 2 CH 3 , J •= 7.5 Hz, 3 J S n . H - 48 Hz), 3.19 (dt, 2H, b i s - a l l y l i c protons, J » 6, 1.5 Hz), 3.73 (s, 3H, -OMe), 4.96 (ddt, IH, H B , J - 10, 1.5, 1 Hz), 4.98 (ddt, IH, H A , J - 17, 1.5, 1 Hz), 5.84 (ddt, IH, H c , J = 17, 10, 6 Hz). In a nOe difference experi-ment, i rradiat ion of the singlet at 6 3.73 (-OMe), caused enhancement of the singlet at 6 0.15 (-SnMe.3). Irradiation of the signal at 6 2.45 (-CH 2CH 3) caused signal enhancement at 6 3.19 (-CH2CH=CH2), 6 0.93 (-CH 2CH 3) and S 0.15 (-SnMe.3). F ina l ly , irradiat ion of the singlet at 6 0.15 (-SnMe3) caused signal enhancement at 6 0.93 (-CH2CH3), S 2.45 - 234 -( - C H 2 C H 3 ) , and 6 3.73 (-OMe). Exact Mass calcd. for C 1 1 H 1 9 0 2 S n (M+-CH3): 303.0407; found: 303.0406. Preparation of methyl (Z)-4-methvl-l-(2-propenyl)-3-trimethvlstannvl- 2-pentenoate (194) Following general procedure 5, to a cold ( - 9 8 ° C ) , s t i rred solution of methyl (Z)-2,3-bis(trimethylstannyl)-4-methyl-pentenoate (126) (1.608 g, 3.52 mmol) in 70 mL of dry THF was added a solution of methyllithium (3.88 mmol) in ether. After the mixture had been s t irred at -78°C for 10 min, 3-iodopropene (10 mmol) was added and the solution was s t i rred at -98°C for 30 min and at -78°C for 45 min. Normal workup, followed by flash column chromatography of the residual o i l on s i l i c a gel (45 g, elution with petroleum ether-diethyl ether; 49:1) and d i s t i l l a t i o n (air-bath temperature 7 0 ° C / 0 . 0 5 Torr) of the residual o i l thus obtained, afforded 849 mg (73%) of the ester (194). This colorless o i l exhibited i r (f i lm): 3081, 1703, 1639, 1277, 1208, 774cm- 1 ; A H nmr (400 MHz, CDCI3) 6: 0.20 (s, 9H, -SnMe3, 2J_s n-H " 5 4 H z ) . 1 - 0 7 ( d . 6 H> (CH 3 ) 2 CH-, J - 7 Hz), 3.07 (septet, IH, (CH 3 ) 2 CH-, J - 7 Hz), 3.21 (dt, 2H, b i s - a l l y l i c protons, J = 6, 1.5 Hz), 3.71 (s, 3H, -OMe), 4.97 (ddt, IH, H A , J - 17, 2, 1.5 Hz), 4.98 (ddt, IH, H B , J - 10, 2, 1.5 Hz), 5.87 - 235 -(ddt, IH, H c , J - 17, 10, 1 Hz). Exact Mass calcd. for C 1 2 H 2 i 0 2 S n (M"1"-CH 3 ) : 317.0563; found: 317.0556. Preparation of methyl (Z)-2-(2-propenvl)-3-trimethylstannyl-2.6- heptadienoate (195) Following general procedure 5, to a cold (-98DC), s t irred solution of methyl (Z)-2,3-bis(trimethylstannyl)-2,6-heptadienoate (133) (2.049 g, 4.378 mmol) in 70 mL of dry THF was added a solution of methyllithium (4.816 mmol) in ether. After the mixture had been s t irred at -98°C for 10 min, 3-iodopropene (8.75 mmol) was added and the solution was s t irred at -98°C for 30 min and at -78°C for 1.5 h. Normal workup, followed by d i s t i l l a t i o n (air-bath temperature 8 0 - 8 5 ° C / 0 . 0 5 Torr) of the residual 011 afforded 1.129 mg (75%) of the ester (195). This colorless o i l exhibited i r (film): 3079, 1700, 1640, 1437, 1284, 1214, 770 cm"1; X H nmr (400 MHz, CDC13) 6: 0.15 (s, 9H, -SnMe3, 2 J S n - H ~ 5 4 Hz>> 1.99-2.07 (m, 2H, CH 2CHCH 2CH 2-), 2.53 (t, 2H, CH 2CHCH 2CH 2, J - 8 Hz, 3 J S n - H " 6 2 Hz), 3.20 (dt, 2H, b i s - a l l y l i c protons, J - 6, 1.5 Hz), 3.74 (s, 3H, -OMe), 4.95-5.08 (m, 4H, v iny l protons), 5.81 (ddt, IH, v iny l proton, J - 17, 10, 6 Hz), 5.84 (ddt, IH, v iny l proton, J - 17, 10, 6 Hz). Exact  Mass calcd. for C 1 3 H 2 1 0 2 S n (M + -CH 3 ): 329.0564; found: 329.0566, - 236 -General Procedure 6: Preparation of cycl ic fl-trimethylstannyl a.B- unsaturated esters and N.N-dimethylamides To a cold ( - 9 8 ° C ) , s t irred solution of the appropriate a lkyl (E) -or (Z)-w-halo-2,3-bis(trimethylstannyl)-2-alkenoates (1 equiv) or the (E) -N,N.-dimethyl- 2,3-bis(trimethylstannyl) - w-bromo-2-alkenamide (1 equiv) in dry THF was added a solution of methyllithium (1.1-1.2 equiv) in ether and hexamethylphosphoramide (2-3 equiv). The resulting yellow solution was s t i rred at -98°C for 1 h (with the exception of one example). Saturated aqueous ammonium chloride (2 mL/mmole) and ether (20 mL/mmole) were added and the mixture was allowed to warm to room temperature. The organic layer was washed three times with saturated aqueous ammonium chloride, dried over anhydrous magnesium sulfate and concentrated. The remaining material was flash chromatographed on s i l i c a gel (elution with petroleum ether-diethyl ether) and the o i l thus obtained was d i s t i l l e d (receiving bulb cooled to -78°C) to afford pure product. Preparation of methyl 2-trimethylstannvl-l-cvclopentenecarboxvlate (205) 205 139 (a) Following general procedure 6, to a cold (-98CC), s t i rred solution - 237 -of the bis(trimethylstannyl) ester (139) (570 mg, 1.065 mmol) in 12 mL of dry THF was added 0.35 mL (2 equiv) of HMPA and a solution of methyl-lithium (1.268 mmol) in ether. After the mixture had been s t irred at -98°C for 50 min, saturated aqueous ammonium chloride and ether were added and the mixture was warmed to room temperature. Normal workup, followed by flash column chromatography of the residual o i l on s i l i c a gel (25 g, elution with petroleum ether-diethyl ether; 14:1) and d i s t i l l a t i o n (air-bath temperature 6 5 ° C / 0 . 1 Torr) of the o i l thus obtained, afforded 231 mg (74%) of the cyc l ic ester (205). This colorless o i l exhibited i r (film): 1700, 1595, 1260, 770 c m - 1 ; -^H nmr (80 MHz, CDC13) 6: 0.16 (s, 9H, -SnMe.3, 2 J S n - H ~ 5 5 H z )> ! - 8 7 (quintet, methylene protons, 2H, J = 7 Hz), 2.60 (t, 4H, a l l y l i c protons, J = 7 Hz), 3.70 (s, 3H, -OMe). Exact Mass calcd. for C 9 H 1 5 0 2 S n (M+-CH3): 275.0094; found: 275.0086. (b) Following general procedure 6, to a cold ( - 9 8 ° C ) , s t irred solution of the bis(trimethylstannyl) ester (138) (4.692 g, 8.06 mmol) in 100 mL of dry THF was added 4.3 mL (3 equiv) of HMPA and a solution of methyl-lithium (9.43 mmol) in ether. Normal workup, followed by column chromatography and d i s t i l l a t i o n as in (a) afforded 1.73 g (73%) of the cyc l i c ester (205). This material was chromatographically (glc and t ic) and spectrally ( i r , ^H nmr) identical with the material prepared in (a). Br 1 38 - 238 -Me 3Sn C0 2Me SnMe 3 Cl (c) Following general procedure 6, the bis(trimethylstannyl) ester (146) (73 mg, 0.148 mmol) was converted into the cyc l ic ester (205). The mixture was s t i rred at -98°C for 30 min and at -78°C for 1.5 h. Normal workup, followed by column chromatography and d i s t i l l a t i o n as in (a) afforded 29 mg (69%) of the cyc l ic ester (205). This material was chromatographically (glc and t ic) and spectrally ( i r , nmr) identical with the material prepared in (a). Preparation of methyl 2-trimethvlstannvl-l-cvclohexenecarboxvlate (206) Following general procedure 6, to a cold ( - 9 8 ° C ) , s t i rred solution of the bis(trimethylstannyl) ester (140) (728 mg, 1.326 mmol) in 15 mL of dry THF was added a solution of methyllithium (1.591 mmol) in ether and 0.43 mL (2 equiv) of HMPA. After the mixture had been s t i rred at -98°C for 50 min, saturated aqueous ammonium chloride and ether were added and the mixture was warmed to room temperature. Normal workup, followed by flash column chromatography of the resultant yellow o i l on Me3Sn SnMe3 206 B r - 239 -s i l i c a ge l (30 g , e l u t i o n with petroleum e t h e r - d i e t h y l e ther ; 17:1) and d i s t i l l a t i o n ( a i r - b a t h temperature 7 0 ° C / 0 . 0 5 Torr ) of the o i l thus obta ined , a f fo rded 289 mg (72%) of the c y c l i c es te r (206). Th is c o l o r l e s s o i l e x h i b i t e d i r ( f i l m ) : 1695, 1240, 770 c m " 1 ; ^ nmr (270 MHz, CDC1 3) 6: 0.14 (s , 9H, -SnMe.3, 2 J_s n -H " 5 5 H z > > 1-52-1.70 (m, 4H, methylene p r o t o n s ) , 2.24-2.46 (m, 4H, a l l y l i c p r o t o n s ) , 3.73 (s , 3H, -OMe). Exact Mass c a l c d . f o r C i o H 1 7 ° 2 S n (M+-CH3): 289.0251; found: 289.0251. Prepara t ion of methyl 2 - t r ime thy ls tannv l - l - cvc lohep tenecarboxy la te (207) Me3Sn C02Me Me3Sn SnMe3 207 Fol lowing general procedure 6, to a c o l d ( -98"C), s t i r r e d s o l u t i o n of the b i s ( t r i m e t h y l s t a n n y l ) es te r (142) (1.308 g, 2.14 mmol) i n 30 mL of dry THF was added 1.1 mL (3 equiv) of HMPA and a s o l u t i o n of methyl-l i t h i u m (2.538 mmol) i n e ther . A f t e r the mixture had been s t i r r e d at - 98 °C f o r 1 h , sa tura ted aqueous ammonium c h l o r i d e and ether were added and the mixture was warmed to room temperature. Normal workup, fo l lowed by f l a s h column chromatography of the r e s u l t a n t crude o i l on s i l i c a ge l (45 g , e l u t i o n wi th petroleum e t h e r - d i e t h y l e ther ; 97:3) and d i s t i l l a -t i o n ( a i r - b a t h temperature 6 5 ° C / 0 . 0 5 Torr ) of the o i l thus obta ined, a f fo rded 394 mg (58%) of the c y c l i c es te r (207). Th is c o l o r l e s s o i l - 240 -exhibited i r (fi lm): 1694, 1583, 1281, 1260, 771 cm'1; X H nmr (270 MHz, CDC13) 6: 0.10 (s, 9H, -SnMe.3, 2 j-Sn-H " 5 4 H z > • 1-35-1.47 (m, 4H, methylene protons), 1.72-1.84 (m, 2H, methylene protons), 2.50-2.57 (m, 2H, a l l y l i c protons), 2.57-2.65 (m, 2H, a l l y l i c protons), 3.70 (s, 3H, -OMe). Exact Mass calcd. for C 1 1 H 1 9 0 2 S n (M + -CH 3 ): 303.0407; found: 303.0407. Preparation of N.N-dimethyl-2-trimethylstannyl-1-cyclopentenecarboxamide  (208) Following general procedure 6, to a cold ( - 9 8 ° C ) , s t irred solution of the bis(trimethylstannyl) amide (175) (146 mg, 0.267 mmol) in 5 mL of dry THF was added 0.1 mL (2 equiv) of HMPA and a solution of methyllith-ium (0.32 mmol) in ether. After the mixture had been s t irred at -98°C for 1 h, saturated aqueous ammonium chloride and ether were added and the mixture was warmed to room temperature. Normal workup, followed by d i s t i l l a t i o n (air-bath temperature 1 1 0 ° C / 0 . 5 Torr) of the residual o i l afforded 57 mg (70%) of the cyc l ic amide (208). This colorless o i l exhibited i r (fi lm): 1636, 1499, 1392, 772 cm"1; X H nmr (400 MHz, CDCI3) 6: 0.14 (s, 9H, -SnMe.3, 2J_Sn-H ~ 5 5 Hz>> X - 9 3 (quintet, 2H, methylene protons, J - 7.5 Hz), 2.51-2.58 (m, 2H, a l l y l i c protons), 2.60-2.68 (m, 2H, a l l y l i c protons), 2.96 (s, 3H, -OMe). Exact Mass calcd. for 208 - 241 -C 1 0 H 1 8 NOSn (M+-CH3): 288.0410; found: 288.0409. VII. Synthesis of stereochemically defined trisubstituted v inyl iodides Preparation of (Z)-2-(2-methvl-2-propenyl)-3-trimethylstannyl-3-cyclo- propyl-2-propen-l-ol (214) To a cold ( - 2 0 ° C ) , s t irred solution of the ester (193) (204 mg, 0.593 mmol) in 15 mL of dry diethyl ether was added LAH (12 mg, 0.30 mmol). The mixture was s t irred at -20°C for 4 h. Sodium sulfate decahydrate (-50 mg) was added and the mixture was warmed to room temperature. Elution of the resulting slurry through a short column of F l o r i s i l (3 g, elution with diethyl ether), followed by concentration of the eluate and d i s t i l l a t i o n (air-bath temperature 9 0 ° C / 0 . 1 Torr) of the o i l thus obtained, afforded 127 mg (68%) of the alcohol (214). This colorless o i l exhibited i r (film): 3373 (br), 3076, 1649, 1606, 1024, 769 cm"1; X H nmr (400 MHz, CDC13) 6: 0.21 (s, 9H, -SnMe.3, 2J_sn-H ~ 5 2 Hz), 0.29-0.35 (m, 2H), 0.73-0.81 (m, 2H), 1.28 (t, IH, J - 6 Hz), 1.40-1.50 (m, IH), 1.76 (s, 3H, v iny l methyl), 3.18 (s, 2H, b i s - a l l y l i c protons), 4.02 (dd, 2H, -CH 20H, J - 6, 1 Hz), 4.69 (d, IH, v iny l proton, J - 1 Hz), 4.79 (d, IH, v iny l proton, J - 1 Hz). Exact Mass calcd. for C 1 2 H 2 i 0 1 1 8 S n (M+-CH3): 298.0530; found: 298.0526. - 242 -Preparation of (Z)-2-(2-methvl-2-propenyl)-3-trimethylstannyl-4-tert- butvldimethylsiloxv-2-buten-1-ol (213) To a s t i rred solution of the ester (189) (221 mg, 0.478 mmol) in 10 mL of dry diethyl ether was added LAH (16 mg, 0.42 mmol). The mixture was s t i rred at room temperature for 18 h. Sodium sulfate decahydrate (-50 mg) was added. Elution of the resulting slurry through a short column of F l o r i s i l (3 g, elution with diethyl ether), followed by concentration of the eluate and d i s t i l l a t i o n (air-bath temperature 110°C/0.05 Torr) of the o i l thus obtained, afforded 130 mg (65%) of the alcohol (213). This colorless o i l exhibited i r (film): 3350 (br), 3060, 1640, 1080, 845, 780 cm"1; X H nmr (400 MHz, CDC13) 6: 0.04 (s, 6H, B^Me^Si-) , 0.21 (s, 9H, -SnMe.3, 2 iSn-H ~ 5 4 H z ) > ° - 8 9 (s> 9 H> Bu t Me 2 Si - ) , 1.26 (t, IH, -OH, J — 6 Hz; addition of D 20 resulted in the disappearance of this signal) , 1.73 (s, 3H, v inyl methyl), 2.92 (s, 2H, b i s - a l l y l i c protons), 3.04 (d, 2H, -CH20H, J - 6 Hz), 3.32 (s, 2H, Bu t Me 2 SiOCH 2 - , 3J_sn-H " 4 8 H z > • 4 - 7 0 <s> 1 H> v i n y l proton), 4.78 (s, IH, v iny l proton). Exact Mass calcd. for CigH330 2SiSn (M+-CH3): 405.1272; found: 405.1280. - 243 -Preparation of (Z)-4-methyl-2-(2-propenvl)-3-trimethylstannyl-2- penten-l-ol (212) To a cold ( - 7 8 ° C ) , s t i rred solution of the ester (194) (840 mg, 2.53 mmol) in 70 mL of diethyl ether was added 6.32 mL (6.32 mmol) of a IM solution of DIBAL in hexane. The mixture was s t irred at -78°C for 1 h and at 0CC for 1 h. Saturated aqueous ammonium chloride (-1 mL) was added and the mixture was allowed to warm to room temperature. The result ing white s lurry was treated with anhydrous magnesium sulfate and then was f i l t e red through a short column of F l o r i s i l (20 g, elution with diethyl ether). Concentration of the combined eluate and d i s t i l l a t i o n (air-bath temperature 7 0 - 7 5 ° C / 0 . 0 5 Torr) of the residual o i l afforded 747 mg (97%) of the alcohol (212). This colorless o i l exhibited i r (fi lm): 3336 (br), 1637, 1031, 772 c m - 1 ; X H nmr (400 MHz, CDC13) 6: 0.24 (s, 9H, -SnMe3, 2 J S n - H " 5 2 H z ) • 1 - 0 0 <d> 6 H> (CH 3 ) 2 CH-, J - 7 Hz), 1.17 (t, IH, -CH 20H, J - 7 Hz), 2.96 (septet, IH, (CH 3 ) 2 CH-, J - 7 Hz), 3.02 (dt, 2H, b i s - a l l y l i c protons, J - 6, 1.5 Hz), 4.04 (d, 2H, -CH 20H, J - 7 Hz), 5.00 (ddt, IH, H B , J - 10, 2, 1.5 Hz), 5.03 (ddt, IH, H A , J - 17, 2, 1.5 Hz), 5.83 (ddt, IH, H c , J - 17, 10, 6 Hz). Exact Mass calcd. for c l l H 2 1 0 S n ( M 4 - - ^ ) : 289.0615; found: 289.0613. - 244 -Preparation of (Z)-2-(2-propenyl)-3-trimethylstannyl-2-penten-l-ol (211) To a cold ( - 7 8 ° C ) , s t irred solution of the ester (179) (1.469 g, 4.63 mmol) in 100 mL of diethyl ether was added 11.58 mL (11.58 mmol) of a 1M solution of DIBAL in hexane. The mixture was s t i rred at -78°C for 1 h and at 0°C for 1.5 h. Saturated aqueous ammonium chloride (~1 mL) was added and the mixture was allowed to warm to room temperature. Normal workup (see p. 243), followed by d i s t i l l a t i o n (air-bath tempera-ture 8 5 - 9 0 ° C / 0 . 0 5 Torr) of the residual o i l afforded 1.262 g (94%) of the alcohol (211). This colorless o i l exhibited i r (film): 3348 (br), 3079, 1637, 1614, 997, 769 cm- 1; 1 H nmr (400 MHz, CDC13) 5: 0.18 (s, 9H, -SnMe3, 2 J S n - H = 5 2 H z > • ° - 9 1 (fc> 3 H> - C H2 C H-3. J_ = 8 Hz) , 1.20 (t, IH, -OH, J = 6 Hz), 2.30 (q, 2H, -CH 2 CH 3 , J = 8 Hz, 3 J S n - H = 6 9 Hz>> 2 • 9 9 (dt, 2H, b i s - a l l y l i c protons, J = 6, 1.5 Hz), 4.05 (d, 2H, -CH 20H, J - 6 Hz), 5.0 (ddt, IH, H B , J = 10, 2, 1.5 Hz), 5.05 (ddt, IH, H A , J - 17, 2, 1.5 Hz), 5.81 (ddt, IH, H c , J = 17, 10, 6 Hz). Exact Mass calcd. for C 1 0 H 1 9 O S n (M+-CH3): 275.0458; found: 275.0456. - 245 -Preparation of (Z) -l-methoxymethoxv-2- (2-propenvl') -3-trimethvlstannyl-2- pentene (215) To a cold ( - 7 8 ° C ) , s t i rred solution of the alcohol (211) (89 mg, 0.307 mmol) in 2 mL of dry dichloromethane was added 320 (5.481 mmol) of N,N-diisopropylethylamine and 69 J J L (0.913 mmol) of methoxymethyl chloride. The mixture was s t irred at 0"C for 10 min and at room temperature for 3 h. It was then concentrated and petroleum ether (15 mL) was added to the residue. The organic solution was then washed three times with saturated aqueous sodium bicarbonate, dried over anhydrous magnesium sulfate and concentrated. Glc analysis indicated that the resultant o i l consisted of 92% of (215) and 7% of the protodestannylated product. Flash column chromatography of this material on s i l i c a gel (15 g, elution with petroluem ether-diethyl ether; 9:1), followed by d i s t i l l a t i o n (air-bath temperature 8 0 - 8 5 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 81 mg (79%) of the ether (215). This colorless o i l exhibited i r (film): 3079, 1638, 1614, 1152, 1037, 769 cm' 1 ; X H nmr (400 MHz, CDC13) 6: 0.18 (s, 9H, -SnMe3, 2 J S n - H - 5 4 Hz), 0.92 (t, 3H, -CH 2 CH 3 , J - 8 Hz), 2.31(q, 2H, -CH 2 CH 3 , J • 8 Hz, 3J-Sn-H - 66 Hz), 2.98 (dt, 2H, b i s - a l l y l i c protons, J - 6, 1.5 Hz), 3.38 (s, 3H, -OMe), 3.96 (s, 2H, -CH2OCH2OMe, 4 J S n . H - 10 Hz), 4.62 (s, 2H, -CH2OCH2OMe), 5.00 (ddt, IH, H B , J - 10, 2, 1.5 Hz), 5.04 (ddt, IH, H A , J - 17, 2, 1.5 Hz), 5.80 (ddt, IH, H c , J -= 17, 10, 6 Hz). Exact Mass - 246 -calcd. for C 1 2 H 2 30 2 Sn (M+-CH3): 319.0720; found: 319.0721. Preparation of (Z)-3-iodo-2-(2-propenvl)-2-penten-l-ol (220) To a s t i rred solution of the v inyl stannane (211) (1.063 g, 3.665 mmol) in 40 mL of dry dichloromethane was added 931 mg (3.665 mmol) of so l id iodine. The mixture was s t irred at room temperature u n t i l a pale yellow color persisted. Concentration of the solution, followed by flash column chromatography of the residual o i l on s i l i c a gel (30 g, elution with petroleum ether-diethyl ether; 7:3) and d i s t i l l a t i o n (air-bath temperature 7 0 - 7 5 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 575 mg (63%) of the iodo alcohol (220). This colorless o i l exhibited i r (fi lm): 3319 (br), 3079, 1638, 1455, 1087, 1010, 828 cm"1; X H nmr (400 MHz, CDCI3) 6: 1.07 (t, 3H, -CH 2 CH 3 , J - 7.5 Hz), 1.64 (t, IH, -OH, J - 6 Hz), 2.61(q, 2H, -CH 2 CH 3 , J - 7.5 Hz), 3.09 (dt, 2H, b i s - a l l y l i c protons, J - 6, 1.5 Hz), 4.24 (d, 2H, -CH 20H, J - 6 Hz), 5.06 (ddt, IH, H B , J - 10, 2, 1.5 Hz), 5.08 (ddt, IH, H A , J - 17, 2, 1.5 Hz), 5.76 (ddt, IH, H c , J - 17, 10, 6 Hz). Exact Mass calcd. for C 8 H 1 3 I O (M+): 252.0013; found: 252.0007. - 247 -Preparation of (Z)-3-iodo-1-(2-methoxvethoxv)methoxy-2-(2-propenyl)- 2-pentene (221) To a s t i rred solution of the iodo alcohol (220) (563 mg, 2.23 mmol) in 15 mL of dry dichloromethane was added 1.17 mL (6.705 mmol) of N,N-diisopropylethylamine and 0.76 mL (6.705 mmol) of 2-methoxyethoxy methyl chloride. The solution was s t irred for 15 h at room temperature and then was concentrated. Petroleum ether (50 mL) was added to the residue. The organic solution was washed three times with saturated aqueous sodium bicarbonate and then was dried over anhydrous magnesium sulfate and concentrated. D i s t i l l a t i o n (air-bath temperature 1 1 5 - 1 2 0 ° C / 0 . 0 5 Torr) of the residual o i l afforded 666 mg (88%) of the ether (221). This colorless o i l exhibited i r (film): 3079, 1639, 1456, 1199-1040 (br), 916 cm"1; -^H nmr (400 MHz, CDC13) 6: 1.09 (t 3H, -CH 2 CH 3 , J - 6 Hz), 2.61 (q, 2H, -CH 2 CH 3 , J - 6 Hz), 3.05 (dt, 2H, b i s - a l l y l i c protons, J - 6, 1.5 Hz), 3.41 (s, 3H, -OMe), 3.55-3.61 (m, 2H), 3.72-3.77 (m, 2H), 4.22 (s, 2H, -CH 2OCH 20-), 4.75 (s, 2H, -CH 2 OCH 2 0-), 5.03 (ddt, IH, H B , J - 10, 2, 1.5 Hz), 5.05 (ddt, IH, H A , J - 17, 2, 1.5 Hz), 5.75 (ddt, IH, H c , J - 17, 10, 6 Hz). Exact Mass calcd. for C 9 H 1 4 I 0 ( M + - C 3 H ? 0 2 ) : 265.0091; found: 265.0082. o - 248 -Preparation of (Z)-3-iodo-4-methvl-2-(2-propenyl)-2-penten-l-ol (222) To a s t i rred solution of the v iny l stannane (212) (736 mg, 2.421 mmol) in 30 mL of dry dichloromethane was added so l id iodine (615 mg, 2.421 mmol). The mixture was s t irred at room temperature u n t i l a pale yellow color persisted. Concentration of the solvent, followed by flash column chromatography of the residual o i l on s i l i c a gel (35 g, elution with petroleum ether-diethyl ether; 7:3) and d i s t i l l a t i o n (air-bath temperature 7 0 - 7 5 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 459 mg (71%) of the iodo alcohol (222). This colorless o i l exhibited i r (fi lm): 3078 (br), 1638, 1617, 1038, 990, cm* 1; X H nmr (400 MHz, CDC13) 6: 0.99 (d, 6H, (CH 3 ) 2 CH-, J - 7 Hz), 1.68 (t, IH, -CH 20H, J = 7.5 Hz), 2.37 (septet, IH, (CH 3 ) 2 CH-, J - 7 Hz), 3.16 (dt, 2H, b i s - a l l y l i c protons, J - 6, 1.5 Hz), 4.27 (d, 2H, -CH 20H, J - 7.5 Hz), 5.06 (ddt, IH, H B , J - 10, 2, 1.5 Hz), 5.07 (ddt, IH, H A , J - 17, 2, 1.5 Hz), 5.80 (ddt, IH, H c , J - 17, 10, 6 Hz). Exact Mass calcd. for C 9 H 1 5 O I (M+) : 266.0169; found: 266.0167. - 249 -Preparation of (Z)-3-iodo-l-(2-roethoxyethoxv)methoxv-4-methyl-2-(2- propenyl)-2-pentene (223) To a s t i rred solution of the alcohol (222) (266 mg, 1 mmol) in 15 mL of dry dichloromethane was added N,N-diisopropylethylamine (0.35 mL, 2 mmol) and 2-methoxyethoxymethyl chloride (0.24 mL, 2 mmol). The solution was s t irred at room temperature for 13 h, and then was concen-trated. Petroleum ether (20 mL) was added to the residue. The organic solution was washed three times with saturated aqueous sodium bicarbo-nate, dried over anhydrous magnesium sulfate and concentrated. D i s t i l -la t ion (air-bath temperature 1006C/0.05 Torr) of the residual o i l afforded 331 mg (93%) of the ether (223). This colorless o i l exhibited i r (f i lm): 3079, 1638, 1620, 1197-992 (br), 850 c m - 1 ; X H nmr (400 MHz, CDC13) 5: 0.97 (d, 6H, (CH 3 ) 2 CH-, J - 7 Hz), 2.38 (septet, IH, (CH 3 ) 2 CH-, J - 7 Hz), 3.12 (dt, 2H, b i s - a l l y l i c protons, J - 6, 1.5 Hz), 3.31 (s, 3H, -OMe), 3.56-3.64 (m, 2H), 3.72-3.79 (m, 2H), 4.26 (s, 2H, -CH 2 0CH 2 0-) , 4.75 (s, 2H, -CH 2OCH 20-), 5.03 (ddt, IH, H B , J - 10, 2, 1.5 Hz), 5.04 (ddt, IH, H A , J - 17, 2, 1.5 Hz), 5.75 (ddt, IH, H c , J - 17, 10, 6 Hz). Exact Mass calcd. for C 9 H 1 4 0 3 I ( M + - C 4 H 9 0 2 ) : 265.0091; found: 265.0088. o— - 250 -Preparation of (Z)-3-iodo-2-(2-propenvl)-2-pentenal (226) H To a s t i rred solution of pyridinium chlorochromate (412 mg, 1.9 mmol) in 4 mL of dry dichloromethane was added sodium acetate (0.47 mmol) and a solution of the alcohol (220) (241 mg, 0.95 mmol) in 2 mL of dry dichloromethane. The brown mixture was s t irred at room temperature for 1 h 45 min and was then poured into 50 mL of diethyl ether. The mixture was passed through a short column of F l o r i s i l (15 g, elution with diethyl ether). Concentration of the eluate, followed by d i s t i l l a -t ion (air-bath temperature 120-125°C/20 Torr) of the residual o i l afforded 196 mg (82%) of the aldehyde (226). This colorless o i l exhibited i r (fi lm): 2859, 1729, 1681, 1274 cm"1; X H nmr (80 MHz, CDC13) 6: 1.18 (t, 3H, -CH 2 CH 3 , J - 7.5 Hz), 2.88 (q, 2H, -CH 2 CH 3 , J = 7.5 Hz), 3.12 (dt, 2H, b i s - a l l y l i c protons, J - 6, 1.5 Hz), 4.80 (ddt, IH, H A , J - 17, 2, 1.5 Hz), 5.00 (ddt, IH, H B , J - 10, 2, 1.5 Hz), 5.70 (ddt, IH, H c , J - .17, 10, 6 Hz), 9.64 (s, IH, -CHO). Exact Mass calcd. for C 8 H i ; L 0I (M+): 249.9856; found: 249.9858. - 251 -Preparation of (E)-5-iodo-4-vinyl-l.4-heptadiene (227) To a s t i rred solution of methylenetriphenylphosphorane (1.9 mmol) in 8 mL of dry THF was added a solution of the aldehyde (226) (189 mg, 0.75 mmol) in 2 mL of dry THF. The red solution was s t irred for 2 h at room temperature. It was then added to 30 mL of petroleum ether and the resultant s lurry was passed through a short column of F l o r i s i l (5 g, elution with petroleum ether). Concentration of the eluate, followed by d i s t i l l a t i o n (air-bath temperature 1 1 0 - 1 1 5 ° C / 0 . 0 5 Torr) of the residual o i l , afforded 146 mg (78%) of the iodo triene (227). This colorless o i l exhibited i r (film): 3080, 1677, 1638, 920 c m - 1 ; X H nmr (400 MHz, CDC13) 6: 1.12 (t, 3H, -CH 2 CH 3 , J = 7.5 Hz), 2.72 (q, 2H, -CH 2 CH 3 , J •= 7.5 Hz), 3.15 (dt, 2H, b i s - a l l y l i c protons, J = 6, 1.5 Hz), 5.02 (ddt, IH, H B , J = 10, 2, 1.5 Hz), 5.04 (ddt, IH, H A , J - 17, 2, 1.5 Hz), 5.16 (d, IH, H E , J - 11 Hz), 5.29 (d, IH, Hp, J = 17 Hz), 5.76 (ddt, IH, H c , J = 17, 10, 6 Hz), 6.69 (dd, IH, H D , J = 17, 11 Hz). Exact Mass calcd. for C 9 H 1 3 I (M+): 248.0064; found: 248.0057. - 252 -Preparation of (Z)-3-iodo-2-(2-propenyl)-2.6-heptadien-l-ol (228) To a cold ( - 7 8 ° C ) , s t irred solution of the ester (195) (1.129 g, 3.28 mL) in 100 mL of dry diethyl ether was added 6.56 mL (6.56 mmol) of a 1 M solution of DIBAL in hexane. The reaction mixture was s t irred at -78°C for 1 h and at 0°C for 2 h. Saturated aqueous ammonium chloride (-2 mL) was added and the mixture was allowed to warm to room temperature. The resulting white slurry was treated with anhydrous magnesium sulfate, and the mixture was passed through a short column of F l o r i s i l (10 g, elution with diethyl ether). The combined eluate was concentrated, affording a colorless o i l . To a s t irred solution of this o i l in 70 mL of dry dichloromethane was added sol id iodine u n t i l a pale purple color persisted. Concentration, followed by column chromatogra-phy of the residual o i l on s i l i c a gel (20 g, elution with petroleum ether-diethyl ether; 3:1) and d i s t i l l a t i o n (air-bath temperature 8 4 - 8 8 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 610 mg (67%) of the iodo alcohol (228). This colorless o i l exhibited i r (film): 3332 (br), 3078, 1640, 1445, 995, 915 c m - 1 ; X H nmr (400 MHz, CDC13) 6: 1.64 (t, 1H,-CH 20H, J - 6 Hz), 2.30 (q, 2H, CH 2CHCH 2CH 2-, J - 6 Hz) 2.65 (t, 2H, CH 2CHCH 2CH 2-, J - 6 Hz), 3.10 (dt, 2H, b i s - a l l y l i c protons, J - 6, 0.5 Hz), 4.25 (d, 2H, -CH 20H, J - 6 Hz), 4.97-5.15 (diffuse m, 4H), 5.78 (ddt, IH, v iny l proton, J - 17, 10, 6 Hz), 5.80 (ddt, IH, v inyl proton, J -= 17, 10, 6 Hz). Exact Mass calcd. for C 1 0 H 1 5 O I (M+): 278.0165; - 253 -found: 278.0167. Preparation of (Z)-3-iodo-2-(2-propenyl)-2.6-heptadienal (229) H To a s t i rred solution of pyridinium chlorochromate (620 mg, 2.87 mmol) in 12 mL of dry dichloromethane was added sodium acetate (0.719 mmol) and a solution of the alcohol (228) (400 mg, 1.438 mmol) in 8 mL of dry dichloromethane. The brown solution was s t irred at room tempera-ture for 1.5 h and then was poured into 100 mL of diethyl ether. The mixture was passed through a short column of F l o r i s i l (15 g, elution with diethyl ether). Concentration of the eluate, followed by d i s t i l l a -t ion (air-bath temperature 7 0 - 7 5 ° C / 0 . 0 5 Torr) of the residual o i l afforded 360 mg (91%) of the aldehyde (229). This pale yellow o i l exhibited i r (film): 3079, 2737, 1680, 1640, 1589, 917 c m - 1 ; X H nmr (300 MHz, CDC13) 6: 2.40 (qd, 2H, CH 2CHCH 2CH 2-, J •= 6, 1 Hz), 2.99 (t, 2H, CH 2CHCH 2CH 2-, J - 6 Hz), 3.16 (dt, 2H, b i s - a l l y l i c protons, J - 6, 1 Hz), 5.00 (ddt, IH, J - 15, 1.5, 1 Hz), 5.02 (ddt, IH, J - 9.5, 1.5, 1 Hz), 5.04 (ddt, IH, J - 9.5, 1.5, 1 Hz), 5.11 (ddt, IH, J - 15, 1.5, 1 Hz), 5.68 (ddt, IH, J - 15, 9.5, 6 Hz), 5.80 (ddt, IH, J - 15, 9.5, 6 Hz), 9.65 (s, IH, -CHO). Exact Mass calcd. for C 1 0 H 1 3 O I (M+) : 276.0012; found: 276.0009. - 254 -Preparation of (Z)-5-iodo-4-vinvl-l.4.8-nonatriene (230) To a s t i rred solution of methylenetriphenylphosphorane (3.17 mmol) in 20 mL of dry THF was added a solution of the aldehyde (229) (339 mg, 1.228 mmol) in 2 mL of dry THF, and the red solution was s t i rred at room temperature for 1 h. The solution was added to 50 mL of petroleum ether and the resultant s lurry was passed through a short column of F l o r i s i l (5 g, elution with petroleum ether). Concentration of the eluate, followed by d i s t i l l a t i o n {.air-bath temperature 6 5 - 7 0 ° C / 0 . 0 5 Torr) of the residual o i l , afforded 300 mg (89%) of the iodo tetraene (230). This colorless o i l exhibited i r (film): 3079, 1640, 1613, 987, 911 cm' 1 ; X H nmr (400 MHz, CDC13) 6: 2.33 (qd, 2H, CH 2CHCH 2CH 2-, J = 6, 1 Hz), 2.77 (t, 2H, CH 2CHCH 2CH 2-, J = 6 Hz), 3.14 (dt, 2H, b i s - a l l y l i c protons, J = 6, 1 Hz), 5.00 (ddt, IH, J - 10, 1.5, 1 Hz), 5.02 (ddt, IH, J - 10, 1.5, 1 Hz), 5.03 (ddt, IH, J - 17, 1.5, 1 Hz), 5.08 (ddt, IH, J = 17, 1.5, 1 Hz), 5.18 (dd, IH, H E , J - 11, 0.5 Hz), 5.30 (dd, IH, Hp, J = 17, 0.5 Hz), 5.75 (ddt, IH, J = 17, 10, 6 Hz), 5.81 (ddt, IH, J - 17, 10, 6 Hz), 6.70 (dd, IH, H D , J - 17, 11 Hz). Exact Mass calcd. for C ^ H ^ I (M+) : 274.0220; found: 274.0222. - 255 -Preparation of (Z)-l-chloro-4-methvl-2-(2-propenvl)-3-trimethylstannyl- 2-pentene (233) To a s t i rred solution of the alcohol (212) (380 mg, 1.25 mmol) in 6 mL of dry carbon tetrachloride was added triphenylphosphine (656 mg, 2.51 mmol) and triethylamine (191 fil, 1.375 mmol). The solution was refluxed for 12 h. Petroleum ether (20 mL) was added and the resulting s lurry was passed through a short column of F l o r i s i l (10 g, elution with petroleum ether). Concentration of the eluate, followed by d i s t i l l a t i o n (air-bath temperature 8 5 - 9 0 ° C / 0 . 0 5 Torr) of the residual o i l afforded 368 mg (91%) of the chloride (233). This colorless o i l exhibited i r (fi lm): 3080, 1638, 914, 774 cm"1; X H nmr (80 MHz, CDC13) 6: 0.27 (s, 9H, -SnMe 3, 2 J_s n -H " 5 2 H z ) > ° - 9 5 (-d> 6 H> (CH 3 ) 2 CH-, J - 7 Hz), 2.95 (septet, IH, (CH 3 ) 2 CH-, J •= 7 Hz), 3.02 (broad d, 2H, b i s - a l l y l i c protons, J = 6 Hz), 4.03 (s, 2H, -CH 2C1, J_sn-H ~ 8 H z ) • 4.85-5.17 (m, 2H, H A , Hg), 5.80 (ddt, IH, H c , J <= 17, 10, 6 Hz). Exact Mass calcd. for C 1 1 H 2 0 3 5 C l S n ( M 4 - - ^ ) : 307.0276; found: 307.0275. Preparation of (Z)-l-chloro-3-iodo-4-methyl-2-(2-propenyl)-2-pentene (234) - 256 -To a s t i rred solution of the vinylstannane (233) (353 mg, 1.096 mmol) in 15 mL of dry dichloromethane was added so l id iodine (278 mg, 1.096 mmol). The solution was s t irred at room temperature u n t i l a pale purple color persisted. It was then passed through a short column of basic alumina (10 g, elution with petroleum ether). Concentration of the eluate, followed by d i s t i l l a t i o n (air-bath temperature 5 5 - 6 0 ° C / 0 . 0 5 Torr) of the residual o i l afforded 306 mg (98%) of the iodide (234). This colorless o i l exhibited i r (fi lm): 3081, 1638, 1613, 919 cm"1; ^ -H nmr (80 MHz, CDC13) 5: 0.95 (d, 6H, (CH 3 ) 2 CH-, J •= 7 Hz), 2.35 (septet, IH, (CH 3)2CH-, J = 7 Hz), 3.15 (dt, 2H, b i s - a l l y l i c protons, J - 6, 1.5 Hz), 4.30 (s, 2H, -CH 2C1), 5.05 (ddt, IH, H A , J — 17, 2, 1.5 Hz), 5.10 (ddt, IH, Hg, J - 10, 2, 1.5 Hz), 5.77 (ddt, IH, H c , J - 17, 10, 6 Hz). Exact Mass calcd. for C 9 H 1 4 3 5 C 1 I (M+) : 283.9831; found: 283.9827. Preparation of ethvl (Z)-2-iodo-3-trimethvlstannvl-2-butenoate (235) To a cold ( - 7 8 ° C ) , s t i rred solution of the ester (124) (338 mg, 0.765 mmol) in 5 mL of dry dichloromethane was added 194 mg (0.765 mmol) of iodine as a solution in 10 mL of dry dichloromethane. After the pale purple mixture had been s t irred at -78°C for 30 min the solution was warmed to room temperature. Concentration, followed by d i s t i l l a t i o n C0 2Et - 257 -(air-bath temperature ~40°C/0.05 Torr) of Me3SnI and then disti l lation (air-bath temperature 80°C/0.05 Torr) of the residual o i l afforded 280 mg (91%) of the stannyl iodide (235). This colorless o i l exhibited ir (film): 1718, 1578, 1220, 1033, 775 cm"1; XH nmr (300 MHz, CDC13) 6: 0.32 (s, 9H, SnMe3, 2J_sn-H " 5 6 H z ) > 1 - 3 2 3H> -OCH2CH3, J = 7 Hz), 2.10 (s, 3H, vinyl methyl, 3J_sn-H " 4 5 H z> • 4 - 2 5 <<1> 2H> -OCH2CH3, J = 7 Hz). In a nOe difference experiment irradiation of the signal at 6 4.25 (-OCH2CH3) caused signal enhancement at S 2.10 (vinyl methyl) and 6 1.32 (-OCH2CH3); 1 3 C nmr (75.6 MHz, CDCI3) 6: -6.9 (q, X±sn-C = 3 4 9 Hz)> 14.1 (q), 26.0 (q, 2 J S n . H - 36 Hz), 61.7 (t), 93.6 (s), 163.7 (s), 164.4 (s). Exact Mass calcd. for C gH 1 40 2ISn (M+-CH3) : 388.9064; found: 388.9064. Preparation of methyl (Z)-2-iodo-3-trimethylstannyl-2-pentenoate (236) To a cold (-78°C), stirred solution of the ester (125) (620 mg, 0.403 mmol) in 20 mL of dry dichloromethane was added 358 mg (1.403 mmol) of iodine. After the pale purple mixture had been stirred at -78°C for 3.5 h the solution was warmed to room temperature. Concentra-tion, followed by disti l lation (air-bath temperature -40°C/0.05 Torr) of Me3SnI and then disti l lation (air-bath temperature 80-85°C/0.05 Torr) of the residual o i l afforded 550 mg (97%) of the stannyl iodide (236). C02Me - 258 -This colorless o i l exhibited i r (film): 1719, 1225, 1031, 778 cm"1; Lti nmr (300 MHz, CDC13) 6: 0.32 (s, 9H, -SnMe3, 2J_s n-H " 5 4 H z ) • ° - 9 6 (-t> 3H, -CH 2 CH 3 , J - 7.5 Hz), 2.48 (q, 2H, -CH 2 CH 3 , J - 7.5 Hz, 3J_s n-H " 5 5 Hz), 3.76 (s, 3H, -OMe). Exact Mass calcd. for CgH^O^Sn (M+-CH;}): 388.9063; found: 388.9063. Preparation of methyl (E)-3-iododimethvlstannvl-2-trimethylstannyl-2- pentenoate (241) To a s t i rred solution of the ester (147) (420 mg, 0.95 mmol) in 15 mL of dry dichloromethane was added 242 mg (0.95 mmol) of iodine. The yellow mixture was s t irred at room temperature for 30 min. Concentra-t ion, followed by d i s t i l l a t i o n (air-bath temperature 1 2 0 - 1 2 5 ° C / 0 . 0 5 Torr) of the residual o i l afforded 446 mg (85%) of the stannane (241). This colorless o i l exhibited i r (film): 1636, 1540, 1283, 776 c m - 1 ; 1 H nmr (300 MHz, CDC13) 6: 0.29 (s, 9H, -SnMe3, 2 J S n - H " 5 5 H z >• ° - 9 5 <s> 6H, -SnMe 2I, 2Isn-H = 6 6 H z > • 1 - 0 3 3 H> -CH 2 CH 3 , J - 7 Hz), 2.85 (q, 2H, -CH 2 CH 3 , J - 7 Hz, 3 J S n - H - 9 0 Hz>> 3 - 8 4 <s> 3H< -PMfe); 1 3 C nmr (75.6 MHz, CDC13) 6: -6.1 (q, ^sn-C ~ 3 4 9 H z> > 4 - 6 l j S n - C ~ 4 6 4 Hz), 15.3 (q, 3 J S n _ c - 7.4 Hz), 33.1 (t, 2 J S n . c - 64 Hz, 3 J S n . c - 37 Hz), 54.0 (q), 139.6 (s), 176.5 (s), 193.0 (s). Exact Mass calcd. for C 1 0 H 2 0 0 2 I S n 2 (M + -CH 3 ) : 538.8554; found: 538.8550. C02Me - 259 -Preparation of (Z)-2-iodo-3-trimethylstannvl-2-penten-l-ol (248) Me 3Sn | W ' >—OH To a cold ( - 7 8 ° C ) , s t irred solution of the ester (236) (534 mg, 1.32 mmol) in 20 mL of dry diethyl ether was added 2.9 mL of a 1M solution of DIBAL in hexane. The mixture was s t i rred at -78°C for 1 h and at 0°C for 1 h. Saturated aqueous ammonium chloride (-1 mL) was added and the mixture was warmed to room temperature. Normal workup (see pg. 243) followed by subjection of the residual o i l to vacuum (0.1 Torr, -45 min) afforded 415 mg (84%) of the alcohol (248). This colorless o i l exhibited i r (film): 3349 (br), 1577, 1020, 773 c m - 1 ; -^H nmr (300 MHz, CDC13) 6: 0.90 (S, 9H, -SnMe3, 2 J S n - H = 5 5 H z >- 1 - 1 6 ( t . 3H, -CH 2 CH 3 , J -7 Hz), 1.54 (t, IH, -CH 20H, J = 6 Hz), 2.23 (qt, 2H, -CH 2 CH 3 , J = 7, 1.5 Hz), 4.26 (dt, 2H, -CH20H, J - 6, 1.5 Hz). Exact Mass calcd. for C 7 H 1 4 OISn(M + -CH 3 ) : 360.9113; found: 360.9121. VII. Synthesis of stereochemically defined tetrasubstituted alkenes General procedure 7 : Preparation of v invl - l i thium reagents and their  reaction with electrophiles To a cold ( - 7 8 ° C ) , s t irred solution of the appropriate v iny l iodide (1 equiv) in dry THF was added a solution of n-butyllithium (1.2-2.2 - 260 -equiv) in hexane. The resulting solution was s t i rred at -78°C for 10-15 min. A large excess of the appropriate electrophile, which had been freshly d i s t i l l e d or had been passed through basic alumina was added, and the mixture was s t irred at -78°C for 10 min-2 h. In some cases the solution was then s t irred at room temperature for up to 7 h. Saturated aqueous ammonium chloride (-2 mL/mmol) and diethyl ether (-30 mL/mmol) were added and the mixture was allowed to warm to room temperature. The organic solution was then washed three times with saturated aqueous ammonium chloride, dried over anhydrous magnesium sulfate and concen-trated. The resulting o i l was either d i s t i l l e d direct ly or was chroma-tographed on s i l i c a gel (elution with petroleum ether-diethyl ether) prior to d i s t i l l a t i o n , thus affording pure product. Preparation of (E)-4-(2-methoxyethoxy)methoxymethyl-5-methvl-l.4- heptadiene (257) Following general procedure 7, to a cold ( - 7 8 ° C ) , s t i rred solution of the iodide (221) (40 mg, 0.1176 mmol) in 2 mL of dry THF was added a solution of n-butylithium (0.2588 mmol) in hexane. After the mixture had been s t i rred at -78°C for 15 min, iodomethane (-3 mmol) was added and the solution was s t i rred at -78°C for 10 min. Normal workup, followed by d i s t i l l a t i o n (air-bath temperature 9 0 ° C / 0 . 0 5 Torr) of the - 261 -residual o i l afforded 25 mg (93%) of the diene (257). This colorless o i l exhibited i r (film): 3077, 1637, 1201 - 950 (br) cm"1; X H nmr (400 MHz, CDC13) 6: 1.00 (t, 3H, -CH 2 CH 3 , J - 7.5 Hz), 1.78 (s, 3H, v iny l methyl), 2.10 (q, 2H, -CH 2 CH 3 , J - 7.5 Hz), 2.89 (broad d, 2H, b i s - a l l y l i c protons, J - 6.5 Hz), 3.40 (s, 3H, -OMe), 3.55-3.60 (m, 2H), 3.69 - 3.75 (m, 2H), 4.07 (s, 2H, -CH 2OCH 20-), 4.71 (s, 2H, -CH 2OCH 20-), 4.97 (ddt, IH, H B , J - 10, 2, 1 Hz), 5.01 (ddt, IH, H A , J - 17, 2, 1 Hz), 5.78 (ddt, IH, H c , J - 17, 10, 6.5 Hz). Exact Mass calcd. for C 1 3 H 2 4 ° 3 (K*">: 228.1725; found: 228.1726. Preparation of (Z) -5-ethvl-4- (2-methoxyethoxv)methoxymethyl-8-methvl- 1.4.7-nonatriene (256) Following general procedure 7, to a cold ( - 7 8 ° C ) , s t irred solution of the iodide (221) (52 mg, 0.1529 mmol) in 5 mL of dry THF was added a solution of n-butyllithium (0.458 mmol) in hexane. After the mixture had been s t i rred at -78°C for 15 min, 1-bromo-3-methyl-2-butene (-3.0 mmol) was added and the solution was s t i rred at -78°C for 30 min. Normal workup, followed by column chromatography of the residual o i l on s i l i c a gel (10 g, elution with petroleum ether-diethyl ether; 3:1) and d i s t i l l a t i o n (air-bath temperature 1 1 0 - 1 1 5 ° C / 0 . 0 5 Torr) of the o i l thus - 262 -obtained, afforded 29 mg (67%) of the triene (256). This colorless o i l exhibited i r (film): 3077, 1637, 1407, 1173 - 960 (br), 850 cm"1; XU nmr (400 MHz, CDC13) 6: 1.00 (t, 3H, -CH 2 CH 3 , J - 7.5 Hz), 1.67 (s, 3H, (CH 3 ) 2 -C-CH-) , 1-69 (s, 3H, ( C H 3 ) 2 - C = C H - ) , 2.06 (q, 2H, -CH 2 CH 3 , J - 7.5 Hz), 2.83 (broad d, 2H, b i s - a l l y l i c protons, J - 7 Hz), 2.89 (broad d, 2H, b i s - a l l y l i c protons, J - 6 Hz), 3.40 (s, 3H, OMe), 3.53-3.59 (m, 2H), 3.68-3.74 (m, 2H), 4.07 (s, 2H, -CH 2 OCH 2 -) , 4.71 (s, 2H, -CH 2 OCH 2 - ) , 4.95-5.05 (m, 3H, v iny l protons), 5.78 (ddt, IH, H c , J - 17, 10, 6 Hz). Exact Mass calcd. for C 1 3 H 2 0 (M+'C^Ho^): 176.1565; found: 176.1562. Preparation of (Z)-5-ethyl-4-(2-methoxvethoxv)methoxvmethvl-l.4- nonadiene (255) Following general procedure 7, to a cold ( - 7 8 ° C ) , s t i rred solution of the iodide (221) (58 mg, 0.1705 mmol) in 5 mL of dry THF was added a solution of n-butyllithium (0.205 mmol) in hexane. After the reaction mixture had been s t i rred at -78°C for 10 min, iodobutane (-3.5 mmol) was added and the solution was s t irred at -78°C for 1 h and at room temperature for 7 h. Normal workup, followed by column chromatography of the residual o i l on s i l i c a gel (10 g, elution with petroleum ether-diethyl ether; 4:1) and d i s t i l l a t i o n (air-bath temperature 9 0 - 9 3 ° C / 0 . 0 5 - 263 -Torr) of the o i l thus obtained, afforded 30 mg (65%) of the diene (255). This colorless o i l exhibited i r (film): 3076, 1636, 1457, 1200-993 (br), 911 cm"1; X H nmr (400 MHz, CDC13) 6: 0.91 (t, 3H, CH3CH 2CH 2CH 2-, J - 7.5 Hz) 0.99 (t, 3H, -CH 2 CH 3 , J - 7.5 Hz), 1.27-1.40 (m, 4H, CH3CH2CH2CH2-) , 2.07 (q, 2H, -CH 2 CH 3 , J - 7.5 Hz), 2.12 (broad t, 2H, CH3CH2CH2CH2- , J - 7.5 Hz), 2.88 (dt, 2H, b i s - a l l y l i c protons, J - 6, 1 Hz), 3.40 (s, 3H, -OMe) 3.55-3.60 (m, 2H), 3.69-3.76 (m, 2H), 4.05 (s, 2H, -CH 2 OCH 2 0-), 4.71 (s, 2H, -CH 2OCH 20-), 4.97 (ddt, IH, Hg, J - 10, 2, 1 Hz), 5.00 (ddt, IH, H A , J - 17, 2, 1 Hz), 5.78 (ddt, IH, H c , J - 17, 10, 6 Hz). Exact Mass calcd. for C 1 2 H 2 i O (M+'C^Ho^): 181.1593; found: 181.1597. Preparation of (Z)-10-chloro-5-ethyl-4-(2-methoxyethoxy)methoxvmethyl- 1,4-decadiene (258) Following general procedure 7, to a cold ( - 7 8 ° C ) , s t i rred solution of the iodide (221) (56 mg, 0.1647 mmol) in 5 mL of dry THF was added a solution of n-butyllithium (0.362 mmol) in hexane. After the reaction had been s t i rred at -78°C for 10 min, 5-chloro-l-iodopentane (-3.5 mmol) was added and the solution was s t i rred at -78°C for 2 h and at room temperature for 6 h. Glc analysis of an aliquot of the crude solution - 264 -indicated that i t contained a 9:1 mixture of (258) and the corresponding trisubstituted alkene having a proton in the place of the ( C l ^ ^ C l moiety. Normal workup, followed by careful d i s t i l l a t i o n of the mixture afforded 38 mg (72%) of the chloro diene (258) (air-bath temperature 1 3 0 - 1 3 5 ° C / 0 . 0 5 Torr) . This colorless o i l exhibited i r (film): 3080, 1637, 1200-960 (br) cm"1; 3-H nmr (400 MHz, CDC13) 6: 0.99 (t, 3H, -CH 2 CH 3 , J - 7.5 Hz), 1.24-1.40 (m, 4H, Hp and H G ) , 1.79 (quintet, 2H, H E , J - 7 Hz), 2.07 (q, 2H, -CH 2 CH 3 , J - 7.5 Hz), 2.13 (t, 2H, H H , J - 7 Hz), 2.88 (dt, 2H, b i s - a l l y l i c protons, J •= 6, 1 Hz), 3.40 (s, 3H, -OMe), 3.53 (t, 2H, H D , J = 7 Hz), 3.56-3.61 (m, 2H), 3.69-3.76 (m, 2H), 4.04 (s, 2H, -CH 2OCH 20-), 4.71 (s, 2H, -CH 2OCH 20-), 4.97 (ddt, IH, Hg, J - 10, 2, 1 Hz), 5.00 (ddt, IH, H A , J - 17, 2, 1 Hz), 5.78 (ddt, IH, E Q , J •= 17, 10, 6 Hz). In a decoupling experiment irradiat ion of the signal at 6 1.79 collapsed the t r i p l e t at S 3.53 to a singlet and altered the multiplet at 6 1.24-1.40. Irradiation of the signal at S 2.88 simplif ied the signals at S 4.97 (dd, J - 10, 2 Hz), S 5.00 (dd, J = 17, 2 Hz) and 5 5.78 (dd, J = 17, 10 Hz). Exact Mass calcd. for C 1 3 H 2 2 0 3 5 C 1 ( M + - C 4 H 9 0 2 ) : 229.1359; found: 229.1365. Preparation of (Z)-5-ethvl-4-vinvl-l.4-nonadiene (259) Following general procedure 7, to a cold ( - 7 8 ° C ) , s t irred solution - 265 -of the iodide (227) (52 mg, 0.2096 mmol) in 5 mL of dry THF was added a solution of n-butyllithium (0.2516 mmol) in hexane. After the reaction mixture had been s t i rred at -78°C for 10 min, iodobutane (-2.5 mmol) was added and the solution was s t irred at -78°C for 2 h and at room temperature for 30 min. Normal workup, followed by d i s t i l l a t i o n (air-bath temperature 90°C/20 Torr) of the residual o i l afforded 20 mg (54%) of the triene (259). This colorless o i l exhibited i r (fi lm): 3083, 1675, 1626, 1458, 895 cm' 1 ; *H nmr (400 MHz, CDC13) 6: 0.92 (t, 3H, -CH2CH2CH2CH3, J - 7 Hz), 1.00 (t, 3H, -CH 2 CH 3 , J - 7.5 Hz), 1.26-1.44 (m, 4H, -CH2CH2CH2CH3), 2.02 (q, 2H, -CH 2 CH 3 , J - 7.5 Hz), 2.19 (t, 2H, -CH2CH2CH2CH3, J - 7 Hz) 3.01 (dt, 2H, b i s - a l l y l i c protons, J - 6, 1.5 Hz), 4.96 (ddt, IH, H B , J - 10, 2, 1.5 Hz), 4.98 (dd, IH, H D , J = 10, 1.5 Hz),- 4.99 (ddt, IH, H A , J — 17, 2, 1.5 Hz), 5.14 (dd, IH, H E , J = 17, 1.5 Hz), 5.83 (ddt, IH, H c , J - 17, 10, 6 Hz), 6.73 (dd, IH, Hp, J - 17, 10 Hz). Exact Mass calcd. for C 1 3 H 2 2 (M+) : 178.1721; found: 178.1719. Preparation of (Z)-5-(3-butenvl)-4-vinvl-l.4.9-decatriene (260) Following general procedure 7, to a cold ( - 7 8 ° C ) , s t i rred solution of the iodide (230) (99 mg, 0.3613 mmol) in 8 mL of dry THF was added a - 266 -solution of n-butyllithium (0.794 mmol) in hexane. After the mixture had been s t i rred at -78°C for 10 min, 5-iodo-l-pentene (-7 mmol) was added and the solution was s t irred at -78°C for 10 min and at room temperature for 4 h. Normal workup, followed by glc analysis of an aliquot of the crude mixture indicated that the lat ter material con-sisted of a 9:1 mixture of the pentaene (260) and the material with a proton in the place of the 4-pentenyl moiety. Careful d i s t i l l a t i o n (air-bath temperature 7 0 - 7 5 ° C / 0 . 0 5 Torr) of the crude o i l afforded, 52 mg (67%) of the pentaene (260). This colorless o i l exhibited i r (fi lm): 3078, 1640, 1465, 991, 911 cm' 1 ; ltt nmr (400 MHz, CDC13) 6: 1.46-1.57 (m, 2H), 2.03-2.37 (diffuse m, 8H), 3.02 (dt, 2H, b i s - a l l y l i c protons, J - 6, 1 Hz), 4.93-5.11 (diffuse m, 7H), 5.17 (dd, IH, H E , J = 17, 1 Hz), 5.76 - 5.91 (diffuse m, 3H), 6.71 (dd, IH, Hp, J - 17, 10 Hz). Exact  Mass calcd. for C 1 6 H 2 4 (M+) : 216.1878; found: 216.1885. General procedure 8: Preparation of vinylcopper (I) reagents and their  reaction with electrophiles To a cold ( - 7 8 ° C ) , s t irred solution of the appropriate v iny l iodide (1 equiv) in dry THF (-30 mL per mmol) was added a solution of n-butyl-l ithium (2.1 equiv) in hexane. The resulting solution was s t i rred at -78°C for 10-15 min. Cuprous(I) bromide*dimethyl sulphide complex (1.1 equiv) was added and the solution was s t i rred at -48°C for 20-30 min. An excess of the appropriate electrophile, which had been passed through basic alumina was added, and the mixture was s t irred at -48°C for 45-60 - 267 -min. Saturated aqueous ammonium c h l o r i d e (pH 8, 2 mL/mmol) and d i e t h y l e ther (-20 mL/mmol) were added and the mixture was v i g o r o u s l y s t i r r e d at room temperature u n t i l a b lue aqueous s o l u t i o n was ev ident . The organic s o l u t i o n was washed three times with saturated aqueous ammonium c h l o r i d e (pH 8 ) , d r i e d over anhydrous magnesium s u l f a t e and concentrated. The crude product was chromatographed on s i l i c a ge l ( e l u t i o n with petroleum e t h e r - d i e t h y l ether) and the r e s u l t i n g o i l was d i s t i l l e d , a f f o r d i n g pure product . P repara t ion of (E) -4-(2-methoxvethoxy)rnethoxvniethvl-5- isopropvl-7- m e t h v l - 1 . 4 . 7 - o c t a t r i e n e (264) Fo l lowing general procedure 8, to a c o l d ( - 7 8 ° C ) , s t i r r e d s o l u t i o n of the iod ide (223) (54 mg, 0.1525 mmol) i n 5 mL of dry THF was added a s o l u t i o n o f n _ b u t y l l i t h i u m (0.38 mmol) i n hexane. A f t e r the mixture had been s t i r r e d at -78°C f o r 10 min, cuprous(I) bromide•dimethyl s u l f i d e complex (35 mg, 0.167 mmol) was added and the s o l u t i o n was s t i r r e d at - 48 °C f o r 30 min. 3-Iodo-2-methylpropene (-1.5 mmol) was added and the s o l u t i o n was s t i r r e d at -48°C f o r 45 min. Normal workup, fo l lowed by column chromatography o f the r e s i d u a l o i l on s i l i c a ge l (5 g , e l u t i o n wi th petroleum e t h e r - d i e t h y l e ther ; 4:1) and d i s t i l l a t i o n - 268 -(air-bath temperature 8 8 - 9 2 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 33 mg (77%) of the triene (264)^ This colorless o i l exhibited i r (f i lm): 3080, 1651, 1637, 1171 - 1045 (br), 900; X H nmr (400 MHz, CDC13) 6: 0.93 (d, 6H, (CH 3 ) 2 CH-, J. - 7 Hz), 1.75 (s, 3H, v iny l methyl), 2.72 (broads, 2H, b i s - a l l y l i c protons), 2.91 (septet, IH, (CH 3 ) 2 CH-, J - 7 Hz), 2.97 (broad d, 2H, b i s - a l l y l i c protons, J_ - 6 Hz), 3.39 (s, 3H, -OMe), 3.53-3.58 (m, 2H), 3.66-3.73 (m, 2H), 3.93 (s, 2H, -CH 2 OCH 2 0-), 4.55 (d, IH, H D , J - 0.5 Hz), 4.67 (s, 2H, -CH 2OCH 20-) 4.73 (d, IH, H D , J - 0.5 Hz), 4.99 (ddt, IH, H B , J - 10, 2, 1 Hz), 5.05 (ddt, IH, H A , J - 17, 2, 1 Hz), 5.83 (ddt, IH, H c , J - 17, 10, 6 Hz). Exact Mass calcd. for C 1 3 H 2 1 0 ( M + - C 4 H 9 0 2 ) : 193.1592; found 193.1587. Preparation of (E)-7-bromo-4-(2-methoxvethoxy)methoxvmethvl-5-iso- propyl-1.4.7-octatriene (265) Following general procedure 8, to a cold ( - 7 8 ° C ) , s t i rred solution of the Iodide (223) (62 mg, 0.175 mmol) in 5 mL of dry THF was added a solution of jj-butyllithium (0.437 mmol) in hexane. After the mixture had been s t i rred at -78°C for 10 min, cuprous(I) bromide*dimethyl sulphide complex (39 mg, 0.192 mmol) was added and the solution was s t i r red at -48°C for 30 min. 2,3-Dibromopropene (-1.75 mmol) was added - 269 -and the solution was s t irred at -48°C for 1 h. Normal workup, followed by column chromatography of the residual o i l on s i l i c a gel (10 g, e lution with petroleum ether-diethyl ether; 4:1) and d i s t i l l a t i o n (air-bath temperature 9 6 - 1 0 0 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 42 mg (70%) of the triene (265). This colorless o i l exhibited i r (f i lm): 3078, 1634, 1200-1039 (br), 910 cm"1; X H nmr (400 MHz, CDC13) 6: 0.98 (d, 6H, (CH 3) 2CH- J - 7 Hz), 2.93 (septet, IH, (CH 3 ) 2 CH-, J - 7 Hz), 2.93 (dt, 2H, b i s - a l l y l i c protons, J - 6.5, 1 Hz), 3.23 (t, 2H, b i s - a l l y l i c protons, J - 1 Hz), 3.41 (s, 3H, -OMe), 3.55-3.61 (m, 2H), 3.68-3.74 (m, 2H), 3.97 (s, 2H, -CH 20CH 20-), 4.68 (s, 2H, -CH 2 OCH 2 0-), 5.01 (ddt, IH, H B , J - 10, 2, 1 Hz), 5.06 (ddt, IH, H A , J - 17, 2, 1 Hz), 5.45 (dt, IH, H D , 1 - 2 , 1 Hz), 5.50 (dt, IH, H D , J - 2, 1 Hz), 5.79 (ddt, IH, H c , J - 17, 10, 6.5 Hz). Exact Mass calcd. for C 1 2 H 1 8 0 7 9 B r ( M + - C 4 H 9 0 2 ) : 257.0542; found: 257.0543. Preparation of (Z)-5-ethvl-4-(2-methoxyethoxy)methoxvmethyl-7-methyl- 1.4.7-octatriene (266) Following general procedure 8, to a cold ( - 7 8 ° C ) , s t i rred solution of the iodide (221) (61 mg, 0.1794 mmol) in 5 mL of dry THF was added a solution of n-butyllithium (0.448 mmol) in hexane. After the mixture had been s t i rred at -78°C for 10 min, cuprous(I) bromide.dimethyl - 270 -sulphide complex (40 mg, 0.1974 mmol) was added and the solution was solution of n-butyllithium (0.448 mmol) in hexane. After the mixture had been s t i rred at -78°C for 10 min, cuprous(I)• bromide dimethyl sulphide complex (40 mg, 0.1974 mmol) was added and the solution was s t i rred at -48°C for 25 min. 3-Iodopropene (~3.5 mmol) was added and the solution was s t i rred at -48°C for 1 h. Normal workup, followed by column chromatography of the residual o i l on s i l i c a gel (10 g, elution with petroleum ether-diethyl ether; 7:3) and d i s t i l l a t i o n (air-bath temperature 1 1 0 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 33 mg (69%) of the triene (266). This colorless o i l exhibited i r (film): 3078, 1637, 1456, 1201-960 (br), 852 cm"1; X H nmr (400 MHz, CDC13) 6: 0.98 (t, 3H, -CH 2 CH 3 , J = 7 Hz), 1.69 (s, 3H, v iny l methyl), 2.07 (q, 2H, -CH 2 CH 3 , J = 7 Hz), 2.85 (s, 2H, b i s - a l l y l i c protons), 2.94 (dt, 2H, b i s - a l l y l i c protons, J = 6, 1 Hz), 3.40 (s, 3H, -OMe), 3.54-3.61 (m, 2H), 3.69-3.75 (m, 2H), 4.03 (s, 2H, -CH 2OCH 20-), 4.64 (d, IH, H D , J -0.5 Hz), 4.70 (s, 2H, -CH 2 0CH 2 0-), 4.75 (d, IH, H D , J — 0.5 Hz), 5.00 (ddt, IH, H B , J = 10, 2, 1 Hz), 5.03 (ddt, IH, H A , J - 17, 2, 1 Hz), 5.79 (ddt, IH, H c , J = 17, 10, 6 Hz). Exact Mass calcd. for C 1 2 H 1 9 0 ( M + - C 4 H 9 0 2 ) : 179.1435; found: 179.1435. Preparation of (Z)-7-bromo-5-ethyl-4-(2-methoxvethoxv)methoxymethyl-- 271 -Following general procedure 8, to a cold ( - 7 8 ° C ) , s t irred solution of the iodide (221) (58 mg, 0.170 mmol) -in 5 mL of dry THF was added a solution of n-butyllithium (0.421 mmol). After the mixture had been s t i r red at -78°C for 10 min, cuprous(I) bromide•dimethyl sulphide complex (38 mg, 0.187 mmol) was added and the solution was s t irred at -48°C for 30 min. 2,3-Dibromopropene (~4 mmol) was added and the solution was s t i rred at -48°C for 1 h. Normal workup, followed by column chromatography of the residual o i l on s i l i c a gel (10 g, elution with petroleum ether-diethyl ether; 4:1) and d i s t i l l a t i o n (air-bath temperature 9 4 - 9 7 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 44 mg (78%) of the triene (267). This colorless o i l exhibited i r (film): 3077, 1635, 1454, 1200-960 (br), 914 cm' 1 ; X H nmr (400 MHz, CDC13) 6: 1.00 (t, 3H, -CH 2 CH 3 , J - 8 Hz), 2.12 (q, 2H, -CH 2 CH 3 , J = 8 Hz), 2.94 (dt, 2H, b i s - a l l y l i c protons), 3.31 (broad s, 2H, b i s - a l l y l i c protons), 3.41 (s, 3H, -OMe), 3.55-3.61 (m, 2H), 3.69-3.75 (m, 2H), 4.05 (s, 2H, -CH 2 0CH 2 0-) , 4.69 (s, 2H,-CH 2OCH 20-), 5.02 (ddt, IH, Hg, J - 10, 2, 1 Hz), 5.07 (ddt, IH, H A , J •= 17, 2, 1 Hz), 5.45 (d, IH, H D , J - 1.5 Hz), 5.56 (dt, IH, H D , J - 1.5, 1 Hz), 5.79 (ddt, IH, H c , J - 17, 10, 6 Hz). Exact Mass calcd. for C 1 1 H 1 6 0 7 9 B r (M+'C^HoO^: 243.0384; found: 243.0391. - 272 -Preparation of (Z)-7-bromo-5-ethyl-4-vinyl-l.4.7-octatriene (268) Following general procedure 8, to a cold ( - 7 8 ° C ) , s t i rred solution of the iodide (227) (42 mg, 0.169 mmol) in 5 mL of dry THF was added n-butyllithium (0.372 mmol) as a solution in hexane. After the reaction mixture had been s t irred at -78°C for 10 min, cuprous(I) bromide-dimethyl sulphide complex (38 mg, 0.1859 mmol) was added and the solution was s t i rred at -48°C for 20 min. 2,3-Dibromopropene (-3.5 mmol) was added and the solution was s t irred at -48°C for 1 h. Normal workup, followed by column chromatography of the residual o i l on s i l i c a gel (10 g, elution with petroleum ether) and d i s t i l l a t i o n (air-bath temperature 130-135°C/20 Torr) of the o i l thus obtained, afforded 30 mg (74%) of the bromo tetraene (268). This colorless o i l exhibited i r (f i lm): 3084, 1676, 1458, 909 cm"1; X H nmr (400 MHz, CDC13) 6: 1.01 (t, 3H, - C H 2 C H 3 , J - 7.5 Hz), 2.18 (q, 2H, -Cfi 2 CH 3 , J - 7.5 Hz), 3.07 (dt, 2H, b i s - a l l y l i c protons, J - 6, 1 Hz), 3.36 (t, 2H, b j ^ - a l l y l i c proton, J_ - 1.5 Hz), 5.00 (ddt, IH, H B , J_ - 10, 2, 1.5 Hz), 5.05 (ddt, IH, H A , J - 17, 2, 1.5 Hz), 5.08 (ddt, IH, H D , J - 10, 1 Hz), 5.23 (dd, IH, H E , J - 17, 1 Hz), 5.45 (dt, IH, H G , J - 1.5, 1 Hz), 5.54 (dt, IH, H G , J -1.5, 1 Hz), 5.83 (ddt, IH, H c , J_ - 17, 10, 6 Hz), 6.61 (dd, IH, Hp, J -17, 10 Hz). In a decoupling experiment irradiat ion of the signal at 6 3,07 s implif ied the signals at 6 5.00 (dd, J - 10, 2 Hz), 6 5.05 (dd, J H - 273 -- 17, 2 Hz), and 6 5.83 (dd, J - 17, 10 Hz). Irradiation of the signal at 6 3.36 simplified the signals at 6 5.45 (d, J - 1.5 Hz) and S 5.54 (d, J - 1.5 Hz). Exact Mass calcd. for C 1 2 H 1 7 ° 7 9 B r '• 240.0514; found: 240.0516. Preparation of the ketone (270) To a cold ( - 7 8 ° C ) , s t irred solution of the iodide (221) (113 mg, 0.332 mmol) in 4 mL of dry THF was added a solution of n-butyllithium (0.731 mmol) in hexane. After the reaction mixture had been s t irred at -78°C for 10 min, magnesium bromide etherate (103 mg, 0.398 mmol) was added and the solution was s t irred at -78°C for 10 min. Dry diethyl ether (8 mL) was added and the white solution was s t i rred at -48°C for 10 min. Copper(I) bromide.dimethyl sulphide complex (17 mg, 0.08 mmol), 2-cyclohexen-l-ene (34 pL, 0.349 mmol) and boron tr i f luor ide etherate (46 ftL, 0.36 mmol) were added and the lime colored solution was s t irred at -78"C for 3 h. Saturated aqueous ammonium chloride (pH 8, -1.0 mL) was added and the solution was allowed to warm to room temperature. The organic solution was washed three times with saturated aqueous ammonium chloride (pH 8), dried over anhydrous magnesium sulfate and concen-trated. Column chromatography of the residual o i l on s i l i c a gel (15 g, - 274 -elution with petroleum ether-diethyl ether; 1:1) and d i s t i l l a t i o n (air-bath temperature 1 4 5 - 1 5 0 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 70 mg (68%) of the ketone (270). This pale yellow o i l exhibited i r (film): 3076, 1714, 1636, 1106, 1045, 913 cm"1; X H nmr (400 MHz, CDC13) 6: 1.04 (t, 3H, -CH 2 CH 3 , J *= 7.5 Hz), 1.64-1.78 (m, 3H), 2.11 (q, 2H, -CH 2 CH 3 , J = 7.5 Hz), 2.07-2.17 (m, IH), 2.22-2.32 (m, 2H), 2.35-2.44 (m, 2H), 2.91 (dt, 2H, b i s - a l l y l i c protons, J - 6, 1 Hz), 3.04-3.12 (m, IH), 3.38 (s, 3H, -OMe), 3.51-3.58 (m, 2H, -0CH 2 CH 2 0-), 3.62-3.73 (m, 2H, -OCH 2CH 20-), 4.04 (s, 2H, -CH 2OCH 20-), 4.68 (s, 2H, -CH 2OCH 20-), 5.00 (ddt, IH, Hg, J = 10, 2, 1 Hz), 5.01 (ddt, IH, H A , J = 17, 2, 1 Hz), 5.78 (ddt, IH, H c , J <= 17, 10, 6 Hz). Exact Mass calcd. for C 1 8 H 3 0 O 4 (M+): 310.2144; found: 310.2142. Preparation of the ketone (271) To a cold ( - 7 8 ° C ) , s t irred solution of the iodide (223) (79 mg, 0.223 mmol) in 2 mL of dry THF was added a solution of n-butyllithium (0.468 mmol) in hexane. After the reaction mixture had been s t irred at -78°C for 10 min, magnesium bromide etherate (63 mg, 0.245 mmol) was added and the solution was s t irred at -48°C for 10 min. Copper(I) - 275 -bromide-dimethyl sulphide complex (11 mg, 0.055 mmol), 2-cyclohex-en-l-one (23 /iL, 0.234 mmol) and boron tr i f luor ide etherate (30 /iL, 0.245 mmol) were added and the lime colored solution was s t irred at -78°C for 3 h. Saturated aqueous ammonium chloride (pH 8, -1.0 mL) was added and the solution was allowed to warm to room temperature. The organic solution was washed three times with saturated aqueous ammonium chloride (pH 8), dried over anhydrous magnesium sulfate and concen-trated. Column chromatography of the residual o i l on s i l i c a gel (10 g, elution with petroleum ether-diethyl ether; 1:1) and d i s t i l l a t i o n (air-bath temperature 150°C/0 .05 Torr) of the o i l thus obtained, afforded 22 mg (31%) of the ketone (271). This colorless o i l exhibited i r (f i lm): 3077, 1713, 1637, 1106, 1045, 912 c m - 1 ; lti nmr (400 MHz, CDC13) 6: 1.04 (t, 3H, (CH 3 ) 2 CH-, J = 7 Hz), 1.07 (d, 3H, (CH 3 ) 2 CH-, J = 7 Hz), 1.60-1.93 (diffuse m,3H), 2.04-2.14 (m, IH), 2.26-2.37 (m, 2H), 2.37-2.45 (m, 2H), 2.57 (broad t, IH, J - 12 Hz), 2.69-2.82 (m, 2H), 2.96 (broad d, 2H, b i s - a l l y l i c protons, J - 6 Hz), 3.38 (s, 3H, -OMe), 3.52-3.58 (m, 2H), 3.66-3.74 (m, 2H), 4.06 (d, IH, -CH 2OCH 20-, J = 9 Hz), 4.17 (d, IH, -CH 2OCH 20-, J •= 9 Hz), 4.71 (s, 2H, -CH 2OCH 20-), 4.97-5.05 (m, 2H, H A and H B ) , 5.77 (ddt, IH, H c , J - 17, 10, 6 Hz). Exact Mass calcd. for C 1 5 H 2 3 0 2 ( M + - C 4 H 9 0 2 ) : 235.1697; found: 235.1697. - 276 -VIII. Synthesis and chemistry of a lkyl (E)-2-(tri-n-butylstannyl)-3-trimethylgermyl-2-alkenoates and a lky l (Z)-3-( tr i -n-butyl -stannyl) -2-trimethylgermyl-2-alkenoates (277) and (278) General Procedure 9: Preparation of compounds (277) and (278) Me3Ge C0 2R' Bu3Sn GeMe3 H H R SnBu 3 R C02R" 277 278 To a one necked, round bottomed flask attached to a condensor was added the appropriate acetylenic ester (1 equiv), tr i-n-butylstannyl-trimethylgermane (276) (1.0-1.5 equiv) and (PPt^^Pd (0.02-0.06 equiv). The mixture was heated to 80-100°C for 5-24 h. Tic analysis of the crude black o i l indicated the presence of the reagent (276) and two products which were readily separated by column chromatography on s i l i c a gel (elution with petroleum ether-diethyl ether). After concentration of the appropriate fractions, the (E) and (Z) isomers (277) and (278), respectively and the recovered tri-n-butylstannyltrimethylgermane (276) were subjected to a vacuum of 0.05 Torr for 1-2 h at room temperature. Preparation of tri-n-butvlstannvltrimethylgermane (276) D-Bu3SnGeMe3 To a cold ( 0 ° C ) , s t i rred solution of lithium diisopropylamide (20.16 mmol) in 75 mL of dry THF was added a solution of tri-n-butylstannane - 277 -(4.48 g, 19.2 mmol) in 10 mL of dry THF. After the reaction mixture had been s t i rred at 0°C for 15 min bromo-trimethylgermane (3.98 g, 20.16 mmol) was added and the colorless solution was s t irred at 0°C for 15 min and at room temperature for 15 min. After the solution had been concen-trated, petroleum ether (100 mL) was added to the residue and the result ing suspension was passed through a short column of F l o r i s i l (20 g, elution with petroleum ether). Concentration of the eluate, followed by d i s t i l l a t i o n (air-bath temperature 1 1 0 ° C / 0 . 0 5 Torr) of the residual o i l , afforded 4.215 g (89%) of the stannylgermane (276). This color-less o i l exhibited i r (film): 2960, 2930, 823 c m - 1 ; X H nmr (270 MHz, CDC13) 6: 0.32 (s, 9H, -GeMe.3), ° - 8 7 9 H> (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-, J = 8 Hz), 0.90 (t, 6H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-, J - 8 Hz), 1.28 (sextet, 6H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-, J - 8 Hz), 1.40-1.53 (m, 6H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-). Exact Mass calcd. for C15H3gGeSn (M +): 408.1060; found: 408.1063. Preparation of ethyl (E)-2-(tri-n-butylstannyl)-3-trimethylgermvl-2- butenoate (279) and ethyl (Z)-3-(tri-n-butvlstannvl)-2-trimethylgermyl- 2-butenoate (280) Me3Ge C0 2Et Bu 3 Sn GeMe3 Me SnBu 3 Me C0 2Et 279 280 Following general procedure 9, to a s t irred mixture of ethyl 2-buty -noate (70) (71 mg, 0.634 mmol) and tri-s-butylstannyltrimethylgermane (276) (0.653 mmol) was added (PPb^^Pd (0.021 mmol) and the mixture was - 278 -s t i rred at 85"C for 24 h. Column chromatography of the black o i l on s i l i c a gel (20 g, elution with petroleum ether-diethyl ether; 17:1) afforded (276) and the esters (279) and (280) as clear colorless o i l s . Subjection of each of the three o i l s to vacuum (0.1 Torr, -1 h) afforded 176 mg (61%) of (279), 53 mg (19%) of (280) and 60 mg (22%) of recovered (276). Compound (279) exhibited i r (film): 1704, 1207, 1042, 829 cm' 1 ; ltt nmr (270 MHz, CDC13) 6: 0.24 (s, 9H, -GeMe.3), 0.87 (t, 9H, (CH 3(CH 2)3)3Sn-, J - 7 Hz), 0.92-1.02 (m, 6H, (CH 3CH 2CH 2CH 2) 3Sn-) , 1.27 (t, 3H, -OCH 2CH 3), J - 7 Hz), 1.20-1.39 (m, 6H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-) , 1.40-1.58 (m, 6H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-), 1.95 (s, 3H, v iny l methyl, 4 J S n - H - 10 Hz), 4.08 (q, 2H, -OCH 2CH 3 , J - 7 Hz); 1 3 C nmr (75.6 MHz, CDCI3) 6: -0.5 (q), 11.6 (t, - 326 Hz), 13.6 (q), 14.2 (q) , 26.6 (q, 3j-Sn-C " 5 0 Hz>> 2 7 - 2 <t. 3 j-Sn-C " 6 0 H z > . 2 8 • 9 2 j-Sn-C " 2 0 H z > -60.1 (t) , 146.0 (s), 161.3 (s), 172.5 (s). Exact Mass calcd. for c 2 0 H 4 1 ° 2 G e S n (M + -CH 3 ): 505.1350; found: 505.1357. Compound (280) exhibited i r (film): 1709, 1560, 1206, 828, 735 cm' 1 ; lH nmr (270 MHz, CDCI3) 8: 0.30 (s, 9H, -GeMe.3), ° - 9 0 ( t « 9H> (CH 3 (CH 2 ) 3 ) 3 Sn- , J - 7 Hz), 0.92-1.00 (m, 6H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-), 1.29 (t, 3H, -OCH 2CH 3), J - 7 Hz), 1.23-1.40 (m, 6H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-), 1.40-1.57 (m, 6H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-), 2.01 (s, 3H, v iny l methyl, 3 J S n . H - 40 Hz), 4.17 (q, 2H, -OCH 2CH 3 , J - 7 Hz); 1 3 C nmr (75.6 MHz, CDCI3) 8: 0.1 (q), 11.3 (t, - 3 2 0 Hz), 13.6 (q), 14.5 (q), 26.7 (q, 2 j-Sn-C " 4 8 H z > . 2 7 - 4 <t. 3 j-Sn-C " 6 2 H z > > 29.1 (t, 2 J S n . c - 19 Hz), 60.0 ( t ) , 149.8 (s), 155.6 (s), 171.8 (s). Exact Mass calcd. for C 2 0 H 4 1 O 2 G e S n (M+-CH3): 505.1349; found: 505.1342. - 279 -Preparation of methvl (E)-4-methyl-2-(tri-n-butylstannyl')-3-trimethvl- germvl-2-pentenoate (281) and methyl (Z)-4-methyl-3-(tri-n-butvl- stannvl)-2-trimethylgermvl-2-pentenoate (282) 282 Following general procedure 9, to a s t i r r e d mixture of methyl 4-methyl-2-pentynoate (115) (65 mg, 0.515 mmol) and t r i - n - b u t y l s t a n n y l -t rime thy 1 germane (276) (0.557 mmol) was added ( P P l ^ ^ P d (0.026 mmol) and the mixture was s t i r r e d at 86-90°C for 24 h. Column chromatography of the black o i l on s i l i c a gel (20 g, e l u t i o n with petroleum ether-d i e t h y l ether; 49:1) afforded (276) and the esters (281) and (282) as c l e a r c o l o r l e s s o i l s . Subjection of each of the three o i l s to vacuum (0.1 Torr, -1 h) afforded 132 mg (48%) of (281), 41 mg (15%) of (282) and 61.5 mg (27%) of recovered (276). Compound (281) exhibited i r ( f i l m ) : 1711, 1555, 1203, 833 cm - 1; XH nmr (400 MHz, CDC13) 6: 0.33 (s, 9H, -GeMe3), 0.90 ( t , 9H, (CH3(CH 2)3) 3Sn-, J - 7 Hz), 0.93-1.00 (m, 6H, (CH 3CH 2CH 2CH 2) 3Sn-), 1.12 (d, 6H, (CH 3) 2CH-, J - 7 Hz), 1.32 (sextet, 6H, (CH 3CH 2CH 2CH 2) 3Sn-, J - 8 Hz), 1.44-1.54 (m, 6H, (CH 3CH 2CH 2CH 2) 3Sn-), 2.34 (septet, IH, Me2CH-, J - 7 Hz), 3.64 (s, 3H, -OMe); I r r a d i a t i o n at 6 1.12 (d) caused collapse of the septet (5 2.34) to a s i n g l e t and showed that 4J.Sn-H ~ 9 Hz; In a nOe difference experiment, i r r a d i a t i o n of the s i n g l e t at 6 0.33 (-GeMe.3) caused s i g n a l enhancement at S 1.12 ((CH 3) 2CH-) and S 3.64 (-OMe). S i m i l a r l y , - 280 -i rradiat ion of the singlet at S 3.64 (-OMe) caused signal enhancement at 6 0.33 (-GeMe3); 1 3 C nmr (75.6 MHz, CDCI3) 5: 2.6 (q), 11.6 (t, ^ s n - c - 325 Hz), 13.6 (q), 22.0 (q), 27.3 (t, 3 J S n - C " 6 2 H z > • 2 8 - 9 2 Isn -C - 20 Hz), 44.6 (d, 3 J S n . c - 52 Hz), 50.8 (q), 145.0 (s), 166.9 (s), 173.1 (s). Exact Mass calcd. for C 2 1 H 4 3 0 2 G e S n (M+-CH3): 519.1506; found: 519.1497. Compound (282) exhibited i r (film): 1714, 1542, 1197, 830 c m - 1 ; X H nmr (400 MHz, CDCI3) 6: 0.32 (s, 9H, -GeMe 3), 0.91(t, 9H, (CH 3(CH 2)3)3Sn-, J = 7 Hz), 1.00 (d, 6H, (CH 3 ) 2 CH-, J - 7 Hz), 0.97-1.05 (m, 6H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn), 1.34 (sextet, 6H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-, J - 8 Hz), 1.43-1.53 (m, 6H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-), 2.68 (septet, IH, (CH 3 ) 2 CH-, J = 7 Hz), 3.67 (s, 3H, -OMe); Irradiation of the doublet at 5 1.00 ((CH.3)2)CH-) caused collapse of the septet (6 2.68) to a singlet and showed that 3J_Sn-H = 80 Hz. In a nOe difference experiment, irradiat ion of the singlet at S 0.32 (-GeMe.3) caused signal enhancement at 5 3.67 (-OMe), whereas irradiat ion of the singlet at 6 3.67 (-OMe) caused signal enhancement at 5 0.32 (-GeMe3) and 6 2.68 ((CH3) 2CH-). Moreover, i rradiat ion of the septet at S 2.68 caused signal enhancement at 5 3.67 (-OMe) and 6 1.00 ((CH 3 ) 2 CH-); 1 3 C nmr (75.6 MHz, CDCI3) 6: 0.6 (q), 13.1 (t, - 3 1 7 Hz), 13.6 (q), 22.5 (q), 27.5 (t, 3 J S n - C - 67 Hz), 29.1 (t, 2 J S n - C " 1 8 H z > . 4 0 - 2 (d. 2^Sn-C " 4 4 - 5 H z > . 5 0 - 8 <q). 1 4 6 - 4 (s), 168.0 (s), 172.8 (s). Exact Mass calcd. for C 2 1 H 4 3 0 2 G e S n (M+'C^): 519.1506; found: 519.1495. - 281 -Preparation of methyl (E)-8-chloro-2-(tri-n-butylstannyl)-3-trimethyl- germyl- 2-octenoate (283) and methyl (Z)-8-chloro-3-(tri-n-butylstannvl) - 2-trimethylgermyl-2-octenoate (284) Following general procedure 9, to a s t irred mixture of methyl 8-chloro-2-octynoate (98) (107 mg, 0.569 mmol) and tri-n-butylstannyl-trimethylgermane (276) (0.764 mmol) was added (PPl^^Pd (0.026 mmol) and the mixture was s t i rred at 92-96°C for 5 h. Column chromatography of the black o i l on s i l i c a gel (20 g, elution with petroleum ether-diethyl ether; 17:1) afforded (276) and the esters (283) and (284) as clear colorless o i l s . Subjection of each of the three o i l s to vacuum (0 .1 Torr, -1 h) afforded 187 mg (55%) of (283), 51 mg (15%) of (284) and 105 mg (33%) of recovered (276). Compound (283) exhibited i r (film): 1708, 1562, 1207, 830, 594 cm"1; lH nmr (400 MHz, CDC13) 6: 0.28 (s, 9H, -GeMe.3), 0.90 (t, 9H, (CH 3(CH 2)3)3Sn-, J « 7 Hz), 0.95-1.00 (m, 6H, (CH 3CH 2CH 2CH 2)3Sn-), 1.32 (sextet, 6H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-, J - 8 Hz), 1.34-1.54 (m, 10H, (CH 3CH 2CH 2CH2)3Sn- and two methylenes), 1.79 (quin-tet, 2H, methylene, J - 7.5 Hz), 2.18-2.26 (m, 2H, a l l y l i c protons), 3.54 (t, 2H, C1CH 2 (CH 2 ) 4 - , J - 7.5 Hz), 3.66 (s, 3H, -OMe); 1 3 C nmr (75.6 MHz, CDCI3) S: 0.4 (q), 11.7 (t, ^ s n . c - 328 Hz), 13.6 (q), 27.1 ( t ) , 27.3 (t, 3 J S n - C - 6 1 H z > ' 2 8 - 9 3 j-Sn-C " 2 0 H z > • 2 9 - 8 (*)> 32.5 (t) , 41.9 (t, 3 j S n C „ 46.8 Hz), 44.7 (t) , 51.1 (q), 145.9 (s), 166.4 - 282 -(s), 172.9 (s). Exact Mass calcd. for C 2 0 H 4 0 O 2 3 5 C l G e S n C 4 H 9 ) : 539.0960; found: 539.0957. Compound (284) exhibited i r (film): 1713, 1551, 1197, 829, 601 cm"1; X H nmr (400 MHz, CDCI3) S: 0.31 (s, 9H, -GeMe3), 0.92 (t, 9H, (CH 3 (CH 2 ) 3 ) 3 Sn- , J - 7 Hz), 0.94-1.00 (m, 6H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-), 1.34 (sextet, 6H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-, J - 8 Hz), 1.39-1.54 (m, 1 0 H , (CH 3 CH 2 CH 2 CH 2 ) 3 Sn- and two methylenes), 1.77 (quintet, 2H, methylene, J - 8 Hz), 2.21-2.27 (m, 2H, a l l y l i c protons), 3.53 (t, 2H, C 1 C H 2 ( C H 2 ) 4 - , J - 7.5 Hz), 3.70 (s, 3H, -OMe); 1 3 C nmr (75.6 MHz, CDCI3) 5: 0.1 (q), 11.6 (t, ^ s n . c " 320 Hz), 13.6 (q), 26.8 (t) , 27.5 (t, 3 J S n . C " 6 2 Hz), 29.1 (t, 2 J S n - C " 1 8 - 5 Hz), 29.5 (t) , 32.3 (t) , 40.8 (t, 2 J S n . c - 45.6 Hz), 44.8 ( t ) , 50.9 (q), 149.2 (s), 160.8 (s), 172.2 (s) . Exact Mass calcd. for C 2 0 H 4 0 0 2 3 5 C l G e S n ( M + - C 4 H 9 ) : 539.0960; found: 539.0949. Preparation of methvl (E) -7- (tert-butyldimethylsiloxv) -2- ( tr i -n-butyl - stannvl)-3-trimethvlgermyl-2-heptenoate (285) and methyl (Z)-7-(tert- butvldimethvlsiloxv)-3-(tri-n-butylstannvl)-3-trimethvlpermyl-2- heptenoate (286) Bu* Me 2SIO Following general procedure 9, to a s t irred mixture of methyl 7-tert-butyldimethylsiloxy-2-heptynoate (118) (172 mg, 0.637 mmol) and - 283 -tri-n-butylstannyltrimethylgermane (276) (0.76 mmol) was added (PPh 3) 4Pd (0.021 mmol) and the mixture was s t irred at 95°C for 14 h. Column chromatography of the black o i l on s i l i c a gel (30 g, elution with petroleum ether-diethyl ether; 24:1) afforded (276) and the esters (285) and (286) as clear colorless o i l s . Subjection of each of the three o i l s to vacuum (0.1 Torr, -1 h) afforded 242 mg (56%) of (285), 58 mg (14%) of (286) and 83 mg (27%) of recovered (276). Compound (285) exhibited i r (f i lm): 1709, 1562, 1211, 1100, 836, 775 c m - 1 ; X H nmr (400 MHz, CDC13) 5: 0.05 (s, 6H, Bu t Me 2 SiO-), 0.27 (s, 9H, -GeMe.3), 0.89 (t, 9H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-, J - 7 Hz), 0.90 (s, 9H, Bu tMe 2SiO-) , 0.93-1.01 (m, 6H, (CH 3CH 2CH 2CH 2)3Sn-), 1.31 (sextet, 6H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-, J - 7.5 Hz), 1.35-1.59 (m, 10H), 2.18-2.26 (m, 2H, a l l y l i c protons), 3.61 (t, 3H, Bu t Me 2 SiOCH 2 - , J - 7 Hz), 3.65 (s, 3H, -OMe); 1 3 C nmr (75.6 MHz, CDCI3) 6": -5.3 (q), 0.3 (q), 11.7 (t, ^Sn-C " 3 3 1 H z ) • 1 3 - 7 <q) . 1 8 - 3 (s), 25.9 (q), 26.9 (t) , 27.3 (t) , 28.9 (t, 2 J S n . C - 19 Hz), 33.2 (t) , 42.0 (t, 3 J S n _ c - 46.7 Hz), 51.1 (q), 62.9 (t) , 145.5 (s), 166.9 (s), 172.9 (s). Exact Mass calcd. for C 2 5 H 5 3 0 3 GeSiSn (M+^Hg): 621.2007; found: 621.2011. Compound (286) exhibited i r (film): 1713, 1557, 1206, 835, 775 c m - 1 ; L H nmr (400 MHz, CDCI3) 6: 0.06 (s, 6H, B^Me^SiO-), 0.31 (s, 9H, -GeMe.3), 0.90 (s, 9H, Bu t Me 2 SiO-), 0.91 (t, 9H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-, J -7 Hz), 0.93-1.00 (m, 6H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-), 1.33 (sextet, 6H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-, J - 7.5 Hz), 1.43-1.55 (m, 10H), 2.20-2.28 (m, 2H, a l l y l i c protons, 3 J . s n - H " 5 2 H z > • 3 - 5 8 2 H> Bu t Me 2 SiOCH 2 - , J - 6.5 Hz), 3.68 (s, 3H, -OMe); 1 3 C nmr (75.6 MHz, CDC13) 6: -5.2 (q), 0.1 (q), 11.6 (t, ^ s n . c - 320 Hz), 13.6 (q), 18.3 (s), 26.0 (q), 26.8 (t, - 284 -3 iSn-C ~ 6 4 Hz>> 2 7 - 5 <t. 2^Sn-C " 1 8 H z ) . 29.1 <t>. 33.0 (t) , 41.1 (t, 2 J S n _ c - 44 Hz), 50.8 (q), 63.1 (t) , 148.9 (s), 161.2 (s), 172.3 (s) . Exact Mass calcd. for C25H5303GeSiSn (M+^Hg): 621.2007; found: 621.2007. Preparation of methvl (E)-6-tetrahvdropvranyloxv-2-(tri-n-butvlstannvl)- 3-trimethvlgermvl-2-hexenoate (287) and methyl (Z)-6-tetrahvdropyranvl- oxv-3-(tri-n-butvlstannyl)-2-trimethylgermvl-2-hexenoate (288) Following general procedure 9, to a s t irred mixture of methyl 6-tetrahydropyranyloxy-2-hexynoate (119) (39 mg, 0.1725 mmol) and t r i -n-butylstannyltrimethylgermane (276) (0.382 mmol) was added (PPl^^Pd (0.009 mmol) and the solution was s t irred at 95°C for 5 h. Column chromatography of the black o i l on s i l i c a gel (15 g, elution with petroleum ether-diethyl ether; 4:1) afforded (276) and the esters (287) and (288) as clear colorless o i l s . Subjection of each of the three o i l s to vacuum (0.1 Torr, -1 h) afforded 55 mg (50%) of (287), 17 mg (15%) of (288) and 86 mg (55%) of recovered (276). Compound (287) exhibited i r (fi lm): 1708, 1562, 1212, 1036, 830 cm"1; X H nmr (400 MHz, CDC13) 6: 0.27 (s, 9H, -GeMe 3), 0.90 (t, 9H, ( C H ^ C ^ C ^ C ^ ^ S n - , J - 7 Hz), 0.96-1.02 (m, 6H, ( C ^ C ^ C ^ C H ^ S n - ) , 1.32 (sextet, 6H, - 285 -(CH 3 CH 2 CH 2 CH 2 ) 3 Sn-, J - 7.5 Hz), 1.44-1.76 (m, 12H), 1.80-1.90 (m, 2H), 2.25-2.40 (m, 2H, a l l y l i c protons), 3.39 (dt, IH, J = 9, 7 Hz), 3.48-3.55 (m, IH), 3.65 (s, 3H, -OMe), 3.75 (dt, IH, J = 9 , 7 Hz), 3.83-3.89 (m, IH), 4.61 (t, IH, J - 4 Hz); 1 3 C nmr (75.6 MHz, CDC13) 6: 0.3 (q), 11.7 (t, ^Sn-C " 3 2 7 H z> • 1 3 - 6 • 1 9 - 3 (*> , 25.4 (t) , 27.2 3 j-Sn-C - 6 1 H z > . 28.9 (t. 2 j-Sn-C " 2 0 H z >- 3 0 - 5 <*> • 3 0 - 6 • 3 8 - 8 (t. 3 j-Sn-C " 4 7 H z > » 5 1 - ° (q). 6 1 - 8 6 7 - ° ( O . 9 8 - 5 (d>- 1 4 6 - ° <s>> 166.1 (s), 172.8 (s). Exact Mass calcd. for C 2 3H4 504GeSn ( M + - C 4 H 9 ) : 577.1561; found: 577.1551. Compound (288) exhibited i r (film): 1713, 1552, 1200, 1123, 829 cm' 1 ; X H nmr (400 MHz, CDCI3) 6: 0.32 (s, 9H, -GeMe.3) - ° - 9 1 ^> 9 H> (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-, J = 7 Hz), 0.97-1.03 (m, 6H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-), 1.34 (sextet, 6H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-, J - 7.5 Hz), 1.45-1.93 (m, 14H), 2.25-2.42 (m, 2H, a l l y l i c protons), 3.36 (dt, IH, J - 9, 6 Hz), 3.45-3.54 (m, IH), 3.69 (s, 3H, -OMe), 3.67-3.75 (m, IH), 3.80-3.90 (m, IH), 4.59 (t, IH, J - 4 Hz); 1 3 C nmr (75.6 MHz, CDCI3) 6: 0.0 (q), 11.6 <t. l j -Sn-C = 3 2 0 H z > . 1 3 - 6 <q)> 1 9 - 4 ( t) . 25.5 (t) , 27.4 (t, 3 J S n . C = 64 Hz), 29.1 (t, 2 j S n C = 20 Hz), 30.4 (t) , 30.6 (t) , 38.0 (t, 2 j S n C = 46 Hz), 50.8 (q), 61.9 (t) , 66.9 (t) , 98.4 (d), 149.5 (s), 160.6 (s), 172.2 (s). Exact Mass calcd. for C23H4504GeSn ( M ^ C ^ HQ ) : 577.1561; found: 577.1551. - 286 -Preparation of methyl (E)-4-(3-cvclohexenyl)-2-(tri-n-butvlstannyl)-3- trimethvlgermvl-2-butenoate (289) and methyl (Z)-4-(3-cyclohexenvl)-3- (tri-n-butylstannyl)-2-trimethylgermyl-2-butenoate (290) Following general procedure 9, to a s t irred mixture of methyl 4-(3-cyclohexenyl)-2-butynoate (121) (141 mg, 0.792 mmol) and t r i - n -butylstannyltrimethylgermane (276) (1.03 mmol) was added (PPt^^Pd (0.024 mmol) and the solution was s t irred at 100°C for 16 h. Column chromatography of the black o i l on s i l i c a gel (30 g, elution with petroleum ether-diethyl ether; 49:1) afforded (276) and the esters (289) and (290) as clear colorless o i l s . Subjection of each of the three o i l s to vacuum (0.1 Torr, -1 h) afforded 246 mg (53%) of (289), 74 mg (16%) of (290) and 113 mg (27%) of recovered (276). Compound (289) exhibited i r (fi lm): 3023, 1708, 1561, 1209, 829, 764 cm' 1 ; lH nmr (400 MHz, CDC13) 6: 0.27 (s, 9H, -GeMe.3), 0.89 (t, 9H, (CH^C^CT^C^^Sn- , J = 7 Hz), 0.94-1.01 (m, 6H, (CH2CH3CH2CH2)3Sn-), 1.09-1.20 (m, IH), 1.31 (sextet, 6H, (CH3CH2CH2CH2)3Sn-, J - 7 Hz), 1.42-1.53 (m, 6H, (CH3CH2CH2CH2)3Sn-), 1.60-1.71 (m, IH), 1.72-1.81 (m, 2H), 1.98-2.09 (m, 3H), 2.14 (dd, IH, a l l y l i c protons, J - 13, 6 Hz), 3.66 (s, 3H, -OMe), 5.53-5.61 (m, 2H, v iny l protons); 1 3 C nmr (75.6 MHz, CDCI3) 5: 0.6 (q), 12.2 (t, ^ s n - C - 3 27 Hz), 13.6 (t) , 25.5 ( t ) , 27.2 (t, 3 J S n . c - 61 Hz), 28.4 ( t ) , 28.9 (t, 2 J S n . c = 19 Hz), 31.9 ( t ) , 33.5 (d), 48.4 (t, 3 J S n - C - 287 -- 4 4 Hz), 51.1 (q), 126.4 (d), 127.1 (d), 147.0 (s), 166.8 (s), 172.6 (s). Exact Mass calcd. for C 2 2 H 4 1 0 2 7 2 G e 1 1 8 S n (M+^Hg) : 529.1334; found: 529.1328. Compound (290) exhibited i r (film): 3022, 1713, 1551, 1201, 828, 735 cm" 1; X H nmr (400 MHz, CDC13) 6: 0.32 (s, 9H, -GeMe 3), 0.90 (t, 9H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-, J - 7 Hz), 0.95-0.98 (m, 6H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-), 1.12-1.22 (m, IH), 1.33 (sextet, 6H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-, J - 7 Hz), 1.42-1.53 (m, 6H, (CH 3CH 2CH 2CH 2) 3Sn-) , 1.64-1.78 (m, 3H), 1.94-2.07 (m, 3H), 2.21 (dd, IH, a l l y l i c protons, J - 12, 7 Hz), 2.31 (dd, IH, a l l y l i c protons, J - 12, 7 Hz), 3.67 (s, 3H, -OMe), 5.63-5.68 (m, 2H, v iny l protons); 1 3 C nmr (75.6 MHz, CDC13) 8: 0.2 (q), 11.8 (t, ^ sn -c =320 Hz), 13.6 (t) , 25.4 (t) , 27.5 (t, 3 J S n - C - 65 Hz), 28.4 (t) , 29.1 (t, 2 ISn-C ° 1 8 H z > . 3 1 - 5 ( t ) . 3 4 - ° <d>. 4 7 - 9 2J-Sn-C = 4 4 H z > . 50.8 (q) , 126.6 (d), 126.8 (d) , 149.8 (s), 160.0 (s), 172.3 (s). Exact Mass calcd. for C 2 2 H 4 1 0 2 7 2 G e 1 1 8 S n (M+^Hg): 529.1334; found: 529.1332. Preparation of (E)-(N).(N)-dimethyl-2-tri-n-butylstannvl-3-trimethvl- germyl-2-butenamide (291) Me 3Ge CONMe 2 Me SnBiig To a s t i rred solution of N,N-dimethyl-2-butynamide (166) (97 mg, 0.873 mmol) and tri-n.-butylstannyltrimethylgermane (276) (353 mg, 0.873 mmol) in 0.5 mL of dry benzene was added (PPh 3) 4Pd (18.3 mg, 0.016 - 288 -mmol). The mixture was stirred at 80°C for 31 h. Flash column chromatography of the black solution on silica gel (25 g, elution with petroleum ether-ethyl acetate; 3:2) afforded (276) and the ester (291) as colorless oils. Subjection of each o i l to vacuum (0.01 Torr, 1 h) afforded 87 mg (19%) of (291) and 253 mg (72%) of recovered (276). The colorless o i l (291) exhibited i r (film): 1625, 1578, 826 cm"1; XH nmr (400 MHz, CDC13) 6: 0.21 (s, 9H, -GeMe3), 0.89 (t, 9H, (CH3CH2CH2CH2)3Sn-, J - 7.5Hz), 0.98 (t, 6H, (CH3CH2CH2CH2)3Sn-, J - 7.5 Hz), 1.33 (sextet, 6H, (CH3CH2CH2CH2)3Sn- , J - 7.5 Hz), 1.45-1.56 (m, 6H, (CH3CH2CH2CH2)3Sn-) , 1.92 (s, 3H, vinyl methyl, 4J_sn-H " 1 1 H z) • 2.90 (s, 3H, -NMe), 2.92 (2, 3H, -NMe). In a nOe difference experiment irradiation of the singlet at 5 0.21 (-GeMe.3) caused enhancement of the singlets at 6 1.92 (vinyl methyl), 6 2.90 (-NMe) and 6 2.92 (NMe). Irradiation of the singlet at 6 1.92 (vinyl methyl) caused signal enhancement at 6 0.21 (-GeMe3) and S 0.98 ((CH3CH2CH2CH2)3Sn-). Finally irradiation of the singlets at 5 2.90 (-NMe) and 5 2.92 (-NMe) caused signal enhancement at 6 0.98 ((CH3CH2CH2CH2)3Sn-) and 6 0.21 (GeMe3): 1 3C nmr (75.6 MHz, CDC13) 8: -1.1 (q), 11.0 (t, ^ sn.c - 320 Hz), 26.2 (q- 3j-Sn-C " 5 4 H z)» 2 7 - 3 (t. 3J.Sn-C - 6 0 H z> • 2 9 0 <c. 2^Sn-C " 2 0 H z> • 34.0 (q), 38.2 (q), 150.5 (s), 150.7 (s), 173.5 (s). Exact Mass calcd. for C 2oH42 O N G e S n (MT^-C^): 504.1509; found: 504.1506. - 289 -Preparation of (Z) -1-phenyl-1-tri-n-butvlstannvl-2-trimethylgermylethene To a s t i rred mixture of phenylacetylene (118 mg, 1.156 mmol) and tri-n-butylstannyltrimethylgermane (276) (506 mg, 1.24 mmol) was added (PPh3)4Pd (32 mg, 0.028 mmol). The mixture was s t i rred for 24 h at 120°C. Flash column chromatography of the resultant black o i l on s i l i c a gel (15 g, elution with hexane) afforded (276) and (292) as colorless o i l s . Subjection of each o i l to vacuum (0.1 Torr, 1 h) afforded 157 mg (27%) of the alkene (292) and 338 mg (67%) of recovered (276). Compound (292) exhibited i r (film): 2957, 1597, 824, 769 cm* 1; X H nmr (400 MHz, CDCI3) 5: 0.31 (s, 9H, -GeMe3), 0.85 (t, 9H, (CH 3CH2CH 2CH2)3Sn-, J - 7.5 Hz), 0.87-0.94 (m, 6H, (CH3CH2CH2CH2)3Sn - ) , 1.26 (sextet, 6H, (CH3CH2CH2CH2)3Sn-, J - 7.5 Hz), 1.35-1.45 (m, 6H, (CH 3 CH2CH 2 CH 2 )3Sn-), 6.78 (s, IH, v iny l proton, 3J_Sn-H = 161 Hz), 6.96-7.01 (m, 2H, aromatic protons), 7.12 (td, IH, aromatic proton, J = 7.5 , 1.5 Hz), 7.27 (m, 2H, aromatic protons); 1 3 C nmr (75.6 MHz, CDCI3) 6: 0.0 (q), 11.7 (t, - \ l S n _ c - 3 20 Hz), 13.6 (q), 27.3 (t, 3 J S n . C - 6 2 Hz), 29.0 (t, 2 J S n - C - 1 9 H z > . 1 2 5 - 4 <d>. 1 2 7 • 9 <d>. 1 4 9 • 5 <d- 2 j-Sn-C -52 Hz), 151.3 (s), 164.2 (s). Exact Mass calcd. for C 2 3H 4 2 GeSn (M+-CH3): 512.1521; found: 512.1518. (292) Bu 3 S n G e M e 3 Ph H - 290 -General Procedure 10: Transmetalation of ethvl (E)-2-( tr i -n-butyl - stannvl)-3-trimethylgermvl-2-butenoate and reaction of the resultant  intermediate with electrophiles To a cold . ( - 9 8 ° C ) , s t irred solution of the appropriate ester (1 equiv) in dry THF (-20 mL per mmol) was added n-butyllithium (1.1-1.2 equiv) as a solution in hexane. The resulting yellow solution was s t i rred at -98°C for 15-20 min. The appropriate electrophile (10-20 equiv), which had been freshly d i s t i l l e d or had been passed through basic alumina was added, and the mixture was st ired at -98°C for up to 45 min unless stated otherwise. Saturated aqueous ammonium chloride (2 mL/mmol) and ether (20 mL/mmol) were added and the mixture was allowed to warm to room temperature. The organic layer was washed three times with saturated aqueous ammonium chloride, dried over anhydrous magnesium sulfate, and concentrated. Column chromatography of the residual o i l on s i l i c a gel (elution with petroleum ether-diethyl ether) and d i s t i l l a t i o n of the o i l thus obtained afforded pure product. Preparation of ethyl (Z)-2-(2-pronenvl)-3-trimethylgermyl-2-butenoate (294) Following general procedure 10, to a cold ( - 9 8 ° C ) , s t i rred solution of the ester (279) (517 mg, 0.994 mmol) in 20 mL of dry THF was added a - 291 -solution of n-butyllithium (1.19 mmol) in hexane. After the mixture had been s t i rred at -98°C for 15 min, 3-iodopropene (-15 mmol) was added and the solution was s t irred at -98°C for 40 min. Normal workup, followed by flash column chromatography of the residual o i l on s i l i c a gel (25 g, elution with petroleum ether-diethyl ether; 24:1) and d i s t i l l a t i o n (air-bath temperature 135°C/10 Torr) of the o i l thus obtained, afforded 216 mg (80%) of the ester (294). This colorless o i l exhibited i r (fi lm): 3081, 1713, 1639, 1273, 1201, 1045, 832 cm* 1; lE nmr (270 MHz, CDC13) 6: 0.27 (s, 9H, -GeMe3), 1.27 (t, 3H, -OCH 2CH 3 , J - 7 Hz), 1.90 (s, 3H, v iny l methyl), 3.16 (d, 2H, b i s - a l l y l i c protons, J - 6 Hz), 4.15 (q, 2H, -OCH 2CH 3 , J - 7 Hz), 4.96 (dd, IH, Hg, J - 10, 2 Hz), 4.98 (dd, IH, H A , J - 17, 2 Hz), 5.78 (dt, IH, H c , J - 17, 10, 6 Hz). In a nOe difference experiment, irradiat ion of the singlet at 5 1.90 (vinyl methyl) caused signal enhancement at 5 5.78 ( H Q ) , S 3.16 ( b i s - a l l y l i c protons) and S 0.27 (-GeMe3). Exact Mass calcd. for C^^H290 2Ge (M+-CH3): 257.0596; found: 257.0593. Preparation of ethyl (Z)-2-methvl-3-trimethylgermvl-2-butenoate (295) Following general procedure 10, to a cold ( - 9 8 ° C ) , s t i rred solution of the ester (279) (179 mg, 0.344 mmol) in 10 mL of dry THF was added a solution of n-butyllithium (0.378 mmol) in hexane. After the mixture - 292 -had been s t i rred at -98DC for 20 min, iodomethane (7 mmol) was added and the solution was s t i rred at -98°C for 45 min. Normal workup, followed by flash column chromatography of the residual o i l on s i l i c a gel (10 g, elution with petroleum ether-diethyl ether; 17:1) and d i s t i l l a t i o n (air-bath temperature 130°C /0.1 Torr) of the o i l thus obtained, afforded 65 mg (77%) of the ester (295). This colorless o i l exhibited i r (f i lm): 1713, 1595, 1270, 1073, 831 cm* 1; lH nmr (270 MHz, CDC13) 6: 0.26 (s, 9H, -GeMe.3), 1.29 (t, 3H, -OCH 2CH 3 , J - 7 Hz), 1.89 (s, 3H, v i n y l methyl), 1.92 (s, 3H, v inyl methyl), 4.16 (q, 2H, OCH 2CH 3, J - 7 Hz). Exact Mass calcd. for CoH 1 70 2Ge (M+-CH3): 231.0440; found: 231.0438. Preparation of ethvl (Z)-2-(3-methvl-2-butenvl)-3-trimethvlgermvl-2- butenoate (296) Following general procedure 10, to a cold ( - 9 8 ° C ) , s t irred solution of the ester (279) (108 mg, 0.207 mmol) in 10 mL of dry THF was added a solution of n-butyllithium (0.249 mmol) in hexane. After the mixture had been s t i rred at -98°C for 20 min, 4-bromo-2-methyl-2-butene (-5 mmol) was added and the solution was s t i rred at -98°C for 45 min. Normal workup, followed by flash column chromatography of the residual o i l on s i l i c a gel (10 g, elution with petroleum ether-diethyl ether; - 293 -17:1) and d i s t i l l a t i o n (air-bath temperature 1 1 0 ° C / 0 . 1 Torr) of the residual o i l thus obtained, afforded 46 mg (74%) of the alkene (296). This colorless o i l exhibited i r (film): 1712, 1590, 1273, 1178, 831 cm' 1 ; X H nmr. (270 MHz, CDC13) 6: 0.25 (s, 9H, -GeMe3) , 1.27 (t, 3H, -0CH 2 CH 3 , J - 7 Hz), 1.66 (br s, 6H, v iny l methyls), 1.90 (s, 3H, v iny l methyl), 3.09 (d, 2H, b i s - a l l y l i c protons, J - 7 Hz), 4.15 (q, 2H, -0CH 2 CH 3 , J - 7 Hz), 4.99 (br t, IH, v iny l proton, J = 7 Hz). Exact  Mass calcd. for C 1 3 H 2 3 0 2 G e (M+-CH3): 285.0910; found: 285.0911. Preparation of ethvl (Z)-2-(3-chloropropvl)-3-trimethvlgermyl-2- butenoate (297) Following general procedure 10, to a cold ( - 9 8 ° C ) , s t irred solution of the ester (279) (125 mg, 0.240 mmol) in 10 mL of dry THF was added a solution of n-butyllithium (0.288 mmol) in hexane. After the mixture had been s t i rred at -98°C for 20 min, 3-chloro-l-iodopropane (-5 mmol) was added and the solution was s t irred at -98°C for 45 min and of -78°C for 1 h. Normal workup, followed by column chromatography of the residual o i l on s i l i c a gel (10 g, elution with petroleum ether-diethyl ether: 17:1) and d i s t i l l a t i o n (air-bath temperature 1 0 0 ° C / 0 . 1 Torr) of the o i l thus obtained, afforded 31 mg (42%) of the chloride (297). This colorless o i l exhibited i r (film): 1712, 1591, 1275, 1135, 831 cm' 1 ; X H C l - 294 -nmr (270 MHz, C D C I 3 ) 5: 0.28 (s , 9H, -GeMe 3 ) , 1.28 ( t , 3H, 0CH 2 CH 3 , J -7 Hz ) , 1.86 (qu in te t , 2H, C1CH 2 CH 2 CH 2 - , J - 7.5 Hz) , 1.94 (s , 3H, v i n y l methy l ) , 2.53 ( t , 2H, C1CH 2 CH 2 CH 2 - , J - 7.5 Hz) , 3.52 ( t , 2H, C 1 C H 2 C H 2 C H 2 - , J. - 7.5 Hz) , 4.16 (q, 2H, -OCH 2 CH 3 , J - 7 Hz) . Exact Mass c a l c d . f o r C n H 2 0 O 2 3 5 C l G e ( M ^ C H ^ : 293.0364; found: 293.0355. Prepara t ion o f e t h v l 2 - m e t h v l - 3 - ( t r i - n - b u t v l s t a n n y l - 2 - t r i m e t h y l g e r m y l - 3 - butenoate (299) To a c o l d ( - 9 8 ° C ) , s t i r r e d s o l u t i o n of e t h y l - ( Z ) - 3 - t r i - n - b u t y l -s tanny l -2 - t r imethy lgermyl -2 -butenoate (280) (138 mg, 0.265 mmol) i n 10 mL of dry THF was added a s o l u t i o n of n - b u t y l l i t h i u m (0.318 mmol) i n hexane. A f t e r the mixture had been s t i r r e d at -98°C f o r 15 min, iodomethane (-5 mmol) was added and the mixture was s t i r r e d at -98°C f o r 45 min and at -78°C f o r 45 min. Normal workup (as i n the previous example) fo l lowed by f l a s h column chromatography of the r e s i d u a l o i l on s i l i c a ge l (10 g , e l u t i o n with petroleum e t h e r - d i e t h y l e ther ; 17:1) and d i s t i l l a t i o n ( a i r - b a t h temperature 1 2 0 ° C / 0 . 0 5 Torr ) o f the o i l thus obta ined , a f fo rded 105 mg (75%) of the es ter (299). Th is c o l o r l e s s o i l e x h i b i t e d i r ( f i l m ) : 1689, 1577, 1252, 1108, 824 c m " 1 ; lU nmr (400 MHz, CDC1 3) 6: 0.20 (s , 9H, -GeMe 3 ) , 0.82-0.93 (m, 6H, ( C H 3 C H 2 C H 2 C H 2 ) 3 S n - ) , SnBu3 Me 3Ge Me - 295 -0.89 (t, 9H, (CH 3(CH 2)3)3Sn-, J - 7.5 Hz), 1.26 (t, 3H, -OCH 2CH 3 , J - 7 Hz), 1.31 (sextet, 6H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-, J - 7 . 5 Hz), 1.41 (s, 3H, Me), 1.39-1.50 (m, 6H, (CH 3 CH 2 CH 2 CH 2 ) 3 Sn-, J - 7 . 5 Hz), 4.06 (dq, IH, -OCH c H D CH' 3 , J H . H - 11 Hz, J H . H . - 7 Hz), 4.17 (dq, IH, -OCHcHrjCH^, C D D l H c - H D - 1 1 H z . J-HD-H' - 7 Hz), 5.27 (d, IH, H A , 3 J S n _ H - 68 Hz, iH^Hg" 1.5 Hz), 5.66 (d, IH, H B , 3 J S n - H " 1 4 6 H z • ^H -H " 1 - 5 H z > « Exact Mass A. fi calcd. for C 2 1 H 4 3 0 2 7 4 G e 1 1 8 S n ( M ^ C ^ ) : 519.1491; found: 519.1492. Preparation of (Z)-2-(2-propenyl)-3-trimethvlgermyl-2-buten-l-ol (304) To a cold ( - 7 8 ° C ) , s t i rred solution of the ester (294) (383 mg, 1.418 mmol) in 15 mL of dry diethyl ether was added 3.12 mL (3.12 mmol) of a IM solution of DIBAL in hexane. The reaction mixture was s t irred at -78°C for 1 h and at 0°C for 2 h. Saturated aqueous ammonium chloride (-1 mL) was added and the mixture was allowed to warm to room temperature. The resulting white s lurry was treated with anhydrous magnesium sulfate and the mixture was f i l t ered through a short column of F l o r i s i l (5 g, elution with diethyl ether). Removal of the solvent from the combined eluate, followed by d i s t i l l a t i o n (air-bath temperature 110°C/10 Torr) of the residual material afforded 327 mg (100%) of the alcohol (304). This colorless o i l exhibited i r (film): 3336 (br), 3079, 1638, 1237, 993, 829 cm"1; X H nmr (400 MHz, CDCI3) S: 0.30 (s, 9H, - 296 --GeMe 3), 1.51-1.60 (broad s, IH, -OH), 1.79 (s, 3H, v iny l methyl), 3.03 (d, 2H, b i s - a l l y l i c protons, J - 7 Hz), 4.09 (s, 2H, -CH2OH), 5.01 (dd, IH, H B , J -= 10, 1.5 Hz), 5.04 (dd, IH, H A , J - 18, 1.5 Hz), 5.84 (ddt, IH, H c , 1 - 18, 10, 7 Hz). Exact Mass calcd. for C 9 H 1 7 0Ge (M+-CH;}): 215.0491; found: 215.0495. Preparation of (Z)-l-methoxymethoxy-2-(2-propenvl)-3-trimethvlgermvl-2- butene (305) To a cold ( 0 ° C ) , s t irred solution of the alcohol (304) (101 mg, 0.439 mmol) in 6 mL of dry dichloromethane was added 66 /iL (0.878 mmol) of chloromethylmethyl ether and 81 nh (0.878 mmol) of ethyldiisopropyl-amine. The reaction mixture was s t irred at 0°C for 1 h and at room temperature for 23 h. The solvent was removed and petroleum ether (5 mL) was added to the residue. The organic layer was washed three times with saturated aqueous sodium bicarbonate, dried over anhydrous magne-sium sulfate and concentrated. D i s t i l l a t i o n (air-bath temperature 7 0 - 7 5 ° C / 0 . 1 Torr) of the residual o i l afforded 79 mg (66%) of the ether (305). This colorless o i l exhibited i r (film): 3079, 1638, 1039, 995, 760 cm"1; X H nmr (400 MHz, CDC13) 6: 0.29 (s, 9H, -GeMe 3), 1.81 (s, 3H, v iny l methyl), 3.00 (d, 2H, b i s - a l l y l i c protons, J = 7 Hz), 3.40 (s, 3H, \ - 297 --CH 2OCH 2OCH 3), 4.01 (s, 2H, -CH 2OCH 2OCH 3), 4.63 (s, 2H, -CH 2OCH 2OCH 3), 5.00 (dd, IH, H A , J - 18, 1.5 Hz), 5.02 (dd, IH, H B , J - 10, 1.5 Hz), 5.79 (ddt, IH, H c , J - 18, 10, 7 Hz). Exact Mass calcd. for C 1 1 H 2 1 0 2 G e (M+-CH3): 259.0754; found: 259.0752. Preparation of (Z)-3-iodo-l-methoxymethoxv-2-(2-propenvl)-2-butene (306) To a s t i rred solution of the ether (305) (55.8 mg, 0.2036 mmol) in 5 mL of dry dichloromethane was added sol id iodine (52 mg, 0.2036 mmol). The mixture was s t irred at room temperature u n t i l a pale purple color persisted and was then passed through a short column of basic alumina (2 g, elution with petroleum ether). Concentration of the combined eluate, followed by d i s t i l l a t i o n (air-bath temperature 6 5 ° C / 0 . 1 Torr) of the residual o i l afforded 47.6 mg (83%) of the iodide (306). This colorless o i l exhibited i r (film): 3079, 1639, 1039, 995, 829 c m - 1 ; X H nmr (400 MHz, CDC13) 5: 2.57 (s, 3H, v inyl methyl), 3.07 (d, 2H, bis-a l l y l i c protons, J - 7 Hz), 3.42 (s, 3H, -CH 20CH 20CH 3), 4.20 (s, 2H, -CH 2OCH 2OCH 3), 4.65 (s, 2H, -CH20CH.20CH3) , 5.04 (dd, IH, H A , J - 15, 1.5 Hz), 5.05 (dd, IH, H B , J - 11, 1.5 Hz), 5.75 (ddt, IH, H c , J - 15, 11, 1.5 Hz). In a nOe difference experiment irradiat ion of the singlet at 6 2.57 (vinyl methyl) caused signal enhancement at 6 5.05 (HB) and 6 5.75 (H c ) . Exact Mass calcd. for C 7 H 1 0 O I (M+'C^O): 236.9778; found: 236.9780. o - 298 -Preparation of (Z)-3-iodo-2-(2-propenvl)-2-buten-l-ol (307) To a s t i rred solution of the alcohol (304) (274 mg, 1.19 mmol) in 10 mL of dry dichloromethane was added so l id iodine (303 mg, 1.19 mmol). The mixture was s t i rred at room temperature u n t i l a pale purple color persisted. Concentration of the solution, followed by column chromato-graphy of the residual o i l on s i l i c a gel (10 g, elution with petroleum ether diethyl ether; 7:3) and d i s t i l l a t i o n (air-bath temperature 50°C/ 0.05 Torr) of the o i l thus obtained, afforded 203 mg (72%) of the iodide (307). This colorless o i l exhibited i r (film): 3371 (br), 3080, 1638, 1057, 916, 759 cm' 1 ; X H nmr (80 MHz, CDC13) 5: 1.58 (t, IH, -OH, J - 7 Hz), 2.58 (s, 3H, v iny l methyl), 3.05 (d, 2H, b i s - a l l y l i c protons, J = 6 Hz), 4.25 (d, 2H, -CH 20H, J - 7 Hz), 5.03 (dd, IH, H A , J - 16, 2 Hz), 5.05 (dd, IH, H B , J — 10, 2 Hz), 5.78 (ddt, IH, H c , J - 16, 10, 6 Hz). Exact Mass calcd. for C 7 H n 0 I (M+) : 237.9857; found: 237.9857. Preparation of (Z)-l-bromo-3-iodo-2-(2-propenvl)-2-butene (308) To a cold ( - 2 0 ° C ) , s t i rred solution of triphenylphosphine (53 mg, - 29  -0.202 mmol) in 3 mL of dry dichloromethane was added 11 /xL (0.222 mmol) of bromine producing a pale yelow solution. Triphenylphosphine was added in very smal amounts until the solution turned clear. A solution of the alcohol (307) (53 mg; 0.202 mmol) in 2 mL of dry CH2C12 was added dropwise over a period of 5 min. After the dropping funnel had ben rinsed with 0.5 mL of CH2C12 the reaction mixture was alowed to warm to rom temperature. The solution was concentrated and petroleum ether (5 mL) was added to the residue. The resultant slurry was pased through a short column of Florisil (2 g, elution with petroleum ether). Concen-tration of the eluate folowed by distilation (air-bath temperature 60°C/0.5 Tor) of the residual oil aforded 56 mg (92%) of the iodo bromide (308). This colorless oil exhibited ir (film): 3080, 1640, 1205, 919 cm"1; 1H nmr (80 MHz, CDC13) 6: 2.58 (s, 3H, vinyl methyl), 3.10 (d, 2H, bis-alylic protons, J - 6 Hz), 4.20 (s, 2H, -CH2Br), 5.05 (dd, IH, HA, J - 16, 2 Hz), 5.08 (dd, IH, HB, J = 10, 2 Hz), 5.78 (ddt, IH, Hc, J = 16, 10, 6 Hz). Exact Mas calcd. for C7H1081BrI (M+): 301.8993; found: 301.8992. XI: Synthesi  of tricyclic and bicyclic ring systems General Procedure 11: Pd(0)-catalyzed intramolecular cyclization of  vinylstannane-vinvl iodides. To stirred dry acetonitrile (2 mL) in a thre-necked round-botmed flask was added triphenylphosphine (0.06 equiv), paladium(l) acetate - 300 -(0.03 equiv) and triethylamine (2 equiv), in that order, and the reaction mixture was heated to 45-50°C for 20-30 min u n t i l a clear red solution persisted. The red solution was transferred (via syringe) to a 10 mL round-bottomed flask equipped with a condenser containing a solution of the appropriate vinylstannane-vinyl iodide (1 equiv) in -0.5 mL of dry acetonitr i le . The resultant mixture was s t i rred at 65-85°C u n t i l t i c analysis of an aliquot indicated complete consumption of the starting material. Concentration of the solution, followed by column chromatography of the residual o i l on s i l i c a gel (elution with petroleum ether-diethyl ether) and d i s t i l l a t i o n of the o i l thus obtained, afforded the appropriate diene. Preparation of compound (313) To a cold ( - 2 0 ° C ) , s t irred solution of lithium diisopropylamide (2.0 equiv) in 5 mL of dry THF was added the ester (206) (122 mg, 0.4018 mmol) as a solution in 5 mL of dry THF and the solution was s t i rred at -20°C for 30 min. HMPA (3 equiv) was added to the yellow solution and the mixture was s t i rred at -20°C for 15 min. The iodo bromide (308) (127 mg, 0.4219 mmol) was added as a solution in 2 mL of dry THF. The - 301 -solution was s t irred at -20°C for 30 min and then saturated aqueous ammonium chloride (-1 mL) was added and the resultant mixture was allowed to warm to room temperature. The organic solution was washed three times with saturated aqueous ammonium chloride, dried over anhydrous magnesium sulfate and concentrated. Flash column chromatogra-phy of the residual o i l on s i l i c a gel (15 g, elution with petroleum ether-diethyl ether; 17:1) and d i s t i l l a t i o n (air-bath temperature 1 5 5 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 145 mg (69%) of the ester (313). This colorless o i l exhibited i r (fi lm): 3030, 1733, 1638, 1212, 769 c m - 1 ; lU nmr (400 MHz, CDC13) 6: 0.15 (s, 9H, -SnMe.3, 2^Sn-H ~ 54 Hz), 1.60-1.79 (m, 3H), 2.01-2.16 (m, 3H), 2.55 (s, 3H, v iny l methyl), 2.58 (d, IH, H E , J - 14 Hz), 2.65 (dd, IH, H D , J - 16, 6 Hz), 3.00 (d, IH, Hg, J - 14 Hz), 3.05 (dd, IH, H D , I - 16, 6 Hz), 3.69 (s, 3H, -OMe), 4.96 (dd, IH, H B , J - 17, 2 Hz), 5.03 (dd, IH, Hg, J - 10, 2 Hz), 5.73 (ddt, IH, H c , J - 17, 10, 6 Hz), 5.99 (t, IH, Hp, J - 3.5 Hz, 3 J S n - H - 74 Hz). Exact Mass calcd. for C 1 7 H 2 6 0 2 I S n (M+-CH3): 509.0001; found: 508.9992. Preparation of l-carbomethoxv-7-methyl-8-(2-propenyl)bicyclof4.3.01- nona-5.7-diehe (314) - 302 -Following general procedure 11, to a s t i rred solution of the vinylstannane-vinyl iodide (313) (48 mg, 0.092 mmol) in 0.5 mL of dry acetonitr i le was added a 2 mL acetonitri le solution of in s i tu generated palladium(O), and the reaction mixture was s t i rred at 80°C for 4 h. Tic analysis of an aliquot indicated the presence of one compo-nent. Concentration, followed by column chromatography (Pasteur pipette) of the residual o i l on s i l i c a gel (2 g, elution with petroleum ether-diethyl ether; 9:1) and d i s t i l l a t i o n (air-bath temperature 5 5 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 17 mg (81%) of the triene (314). This colorless o i l exhibited i r (film): 1723, 1637, 1160, 913 cm"1; lH nmr (400 MHz, CDC13) 6: 1.43-1.52 (m, IH), 2.33-2.42 (m, IH), 2.39 (d, IH, H E , J - 16 Hz), 2.68 (d, IH, H E , J - 16 Hz), 2.88 (d, 2H, H D , J - 6.5 Hz), 3.65 (s, 3H, -OMe), 4.98 (dq, IH, Hg, J = 10, 1.5 Hz), 4.99 (dq, IH, H A , J - 17, 1.5 Hz), 5.47 (t, IH, Hp, J - 4 Hz), 5.72 (ddt, IH, H c , J - 17, 10, 6.5 Hz). Exact Mass calcd. for C 1 5 H 2 o 0 2 (M+): 232.1464; found: 232.1464. To a cold ( - 2 0 ° C ) , s t irred solution of lithium diisopropylamide (2.0 - 303 -equiv) in 3 mL of dry THF was added the ester (207) (47 mg, 0.375 mmol) as a solution in 3 mL of dry THF and the solution was s t i rred at -20°C for 15 min. HMPA (3 equiv) was added to the yellow solution and the mixture was s t i rred for 15 min at -20°C. A solution of the bromo iodide (308), in 2 mL of dry THF was added. The solution was s t i rred for 1 h at -20°C and then saturated aqueous ammonium chloride (-1 mL) was added and the resultant mixture was allowed to warm to room temperature. The organic solution was washed three times with saturated aqueous ammonium chloride, dried over anhydrous magnesium sulfate and concentrated. Flash column chromatography of the residual o i l on s i l i c a gel (10 g, elution with petroleum ether-diethyl ether; 17:1) and d i s t i l l a t i o n (air-bath temperature 1 6 0 - 1 6 5 ° C / 0 . 0 1 Torr) of the o i l thus obtained, afforded 40 mg (51%) of the ester (315). This colorless o i l exhibited i r (film): 3050, 1705, 1638, 1430, 1210, 770 cm' 1 ; X H nmr (400 MHz, CDC13) 6: 0.13 (s, 9H, -SnMe3, 2 J S n - H - 52 Hz), 1.51-1.60 (m, 2H), 1.74-1.85 (m, 2H), 1.95 (ddd, IH, J - 15, 10, 4 Hz), 2.02-2.15 (m, 2H), 2.26-2.37 (m, IH), 2.56 (s, 3H, v iny l methyl), 2.70 (dd, IH, H D , J - 16, 6.5 Hz), 2.73 (d, IH, H E , J - 14 Hz), 3.03 (d, IH, H E , J - 14 Hz). 3.07 (dd, IH, H D , I -16, 6.5 Hz), 3.69 (s, 3H, -OMe), 4.95 (ddt, IH, H A , J = 17, 1.5, 1 Hz), 5.02 (ddt, IH, Hg, J - 10, 1.5, 1 Hz), 5.63 (ddt, IH, H c , J - 17, 10, 6.5 Hz), 6.00 (dd, IH, Hp, J - 7.5, 5.5 Hz, 3 J S n - H " 8 3 H z ) - Exact Mass calcd. for C 1 8 H 2 802lSn (M+-CH3): 523.0158; found: 523.0167. - 304 -Preparation of l-carbomethoxv-8-methvl-9- (2-propenvl)bicvclo f 5 . 3 .01 - deca-6.8-diene (316) Following general procedure 11, to a s t i rred solution of the vinylstannane-vinyl iodide (315) (36 mg, 0.061 mmol) in 0.5 mL of dry acetonitr i le was added a 2 mL acetonitri le solution of in s i tu generated palladium(O), and the reaction mixture was s t irred at 70-75°C for 2.5 h. Tic analysis of an aliquot indicated the presence of one component. Concentration, followed by column chromatography (Pasteur pipette) of the residual o i l on s i l i c a gel (2 g, elution with petroleum ether-diethyl ether; 9:1) and d i s t i l l a t i o n (air-bath temperature 5 5 - 6 0 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 14 mg (85%) of the triene (316). This colorless o i l exhibited i r (film): 1723, 1638, 1440, 1170 cm"1; X H nmr (400 MHz, CDC13) 6: 1.32 (qt, IH, J - 12, 3 Hz), 1.40 (td, IH, J = 13, 2.5 Hz), 1.59-1.79 (m, 2H), 1.66 (s, 3H, v iny l methyl), 1.85-1.95 (m, IH), 2.05-2.26 (m, 3H), 2.40 (d, IH, H E , J - 16 Hz), 2.73 (d, IH, Hg, J — 16 Hz), 2.80-2.95 (m, 2H), 3.71 (s, 3H, -OMe), 4.98 (ddt, IH, Hg, J - 10, 2, 1 Hz), 5.00 (ddt, IH, H A , J - 17, 2, 1 Hz), 5.68 (dd, IH, Hp, J - 9.5 Hz), 5.73 (ddt, lH , H c , J - 17, 10, 6.5 Hz). Exact Mass calcd. for C 1 6 H 2 202 (M+) : 246.1619; found: 246.1621. - 305 -Preparation of compound (317) To a cold ( - 2 0 ° C ) , s t irred solution of lithium diisopropylamide (2.1 equiv) in 3 mL of dry THF was added the ester (205) (58 mg, 0.20 mmol) as a solution in 3 mL of dry THF and the solution was s t i rred at -20°C for 30 min. HMPA (3 equiv) was added to the yellow solution and the mixture was s t i rred at -20°C for 15 min. The iodo bromide (308) (69 mg, 0.229 mmol) was added as a solution in 2 mL of dry THF. The solution was s t i rred at -20°C for 1 h and then saturated aqueous ammonium chloride (1 mL) was added and the resultant mixture was allowed to warm to room temperature. The organic layer was washed three times with saturated aqueous ammonium chloride, dried over anhydrous magnesium sulfate and concentrated. Flash column chromatography of the residual yellow o i l on s i l i c a gel (10 g, elution with petroleum ether-diethyl ether; 97:3) followed by d i s t i l l a t i o n (air-bath temperature 1 4 0 - 1 4 5 ° C / 0.05 Torr) of the o i l thus obtained, afforded 67 mg (66%) of the ester (317). This colorless o i l exhibited i r (film): 3080, 1720, 1639, 1230, 771 cm"1; X H nmr (400 MHz, CDCl 3) 6: 0.17 (s, 9H, -SnMe.3, 2 J S n _ H " 54 Hz), 2.0 (ddd, IH, H H , J - 13, 8, 4 Hz), 2.29 (ddd, IH, H H , J - 13, 8, 6.5 Hz), 2.44-2.61 (m, 2H, H G ) , 2.50 (d, IH, H E , J - 14 Hz), 2.55 (s, 3H, v iny l methyl), 2.67 (dd, IH, H D , 1 - 15.5, 6.5 Hz), 3.02 (dd, IH, H D , J - 15.5, 6.5 Hz), 3.04 (d, IH, H E , J_ - 14 Hz), 3.68 (s, 3H, -OMe) , - 306 -4.97 (ddt, IH, H A , J - 17.5, 2.5, 1.5 Hz), 5.02 (ddt, IH, H B , J - 10, 2.5, 1.5 Hz), 5.63 (ddt, IH, H c , J_ - 17.5, 10.5, 6.5 Hz), 5.98 (t, IH, H F , J - 2.5 Hz, 3J_Sn-H " 3 8 H z >- Irradiation of the t r i p l e t at 6 5.98 simplif ied the multiplet at S 2.44-2.61. Irradiation of the signal at S 5.63 simplif ied the signal at 6 2.67. to a doublet (J - 15.5 Hz) and the signal at S 3.02 to a doublet (J - 15.5 Hz). Moreover, irradiat ion of the signal at S 5.63 simplified the signals at S 4.97 and 6 5.02 to a dt (J - 2.5, 1.5 Hz). Exact Mass calcd. for C 1 6 H 2 40 2 ISn (M+-CH3): 494.9845; found: 494.9838. Preparation of 1-carbomethoxy-4-methyl - 3- (2 - propenvDbicyclo f 3. 3 . 01 - octa-3.5-diene (318) Following general procedure 11, to a s t irred solution of the v iny l -stannane-vinyl iodide (317) (39 mg, 0.078 mmol) in 0.5 mL of dry aceto-n i t r i l e was added a 2 mL acetonitri le solution of in s i tu generated palladium(O) and the reaction mixture was s t i rred at 65-70°C for 30 h. Tic analysis of an aliquot showed two dist inct spots. Concentration of the mixture gave an o i l , which was subjected to column chromatography (Pasteur pipette) on s i l i c a gel (2 g, elution with petroleum ether-diethyl ether; 17:1). The fractions containing the less polar mate-- 307 -r ia l ( s ) were found to contain a mixture of unidentified compounds. The fractions containing the more polar compound were combined and concen-trated. The residual o i l was d i s t i l l e d (air-bath temperature 5 0 ° C / 0 . 0 5 Torr) affording 9.5 mg (55%) of the triene (318). This colorless o i l exhibited i r (fi lm): 1728, 1639, 1165 cm"1; lH nmr (400 MHz, CDCl 3) 6: 1.75 (s, 3H, v iny l methyl), 1.79 (ddd, IH, J - 12, 10, 8.5 Hz), 2.15 (d, IH, Hg, J - 16 Hz), 2.36 (dd, IH, H D , J - 12, 6.5 Hz), 2.52 (ddd, IH, J - 17, 8, 3.5 Hz), 2.75 (d, IH, H E , J - 16 Hz), 2.81-2.96 (m, 3H), 3.59 (s, 3H, -OMe), 5.00 (ddt, IH, H B , J - 10, 2, 1.5 Hz), 5.03 (ddt, IH, H A , J «= 17, 2, 1.5 Hz), 5.39 (br s, IH, Hp), 5.74 (ddt, IH, H c , J - 17, 10, 6.5 Hz). Exact Mass calcd. for C 1 4 H 1 8 0 2 (M+): 218.1307; found: 218.1306. Preparation of (2-trimethvlstannyl-l-cyclopentenyl)methanol (323) To a cold ( - 7 8 ° C ) , s t i rred solution of the ester (205) (2.83 g, 9.56 mmol) in 60 mL of dry diethyl ether was added 24.0 mL (24.0 mmol) of a 1M solution of DIBAL in hexane. The mixture was s t i rred at -78°C for 1 h and at 0°C for 2 h. Saturated aqueous ammonium chloride (-3 mL) was added and the mixture was allowed to warm to room temperature. The result ing white s lurry was treated with anhydrous magnesium sulfate and was then f i l t e red through a short column of F l o r i s i l . The column was - 308 -eluted with further volumes of ether. Concentration of the combined eluate, followed by d i s t i l l a t i o n (air-bath temperature 5 5 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 2.506 g (100%) of the alcohol (323). This colorless o i l exhibited i r (film): 3343(br), 1619, 1055, 770 c m 4 ; % nmr (270 MHz, CDCl 3) 6: 0.16 (s, 9H, -SnMe3, 2 J S n - H " 5 4 H z ) • 1 - 2 9 (t, IH, -OH, J - 6 Hz), 1.88 (quintet, 2H, J - 7 Hz), 2.37-2.51 (m, 4H), 4.23 (d,2H, CH20H, J - 6 Hz). Exact Mass calcd. for C g H 1 5 0Sn (M+-CH3): 247.0145; found: 247.0153. Preparation of (2-iodo-l-cvclopentenvl)methanol (324) To a s t i rred solution of the vinylstannane (323) (2.50 g, 9.564 mmol) in 70 mL of dry dichloromethane was added so l id iodine (2.455 g, 9.57 mmol). The mixture was s t irred at room temperature u n t i l a pale purple color persisted. The solution was concentrated and the resulting o i l was passsed through a short column of basic alumina (10 g, elution with ether). Concentration of the combined eluate, followed by d i s t i l -la t ion of Me3SnI (air-bath temperature 3 0 - 4 0 ° C / 0 . 0 5 Torr) then d i s t i l l a t i o n (air-bath temperature 7 5 - 8 0 ° C / 0 . 0 5 Torr) of the residual o i l afforded 1.88 g (88%) of the iodide (324). This colorless o i l exhibited i r (fi lm): 3310 (br), 1639, 1034 cm"1; X H nmr (270 MHz, CDC13) 6: 1.46 (t, IH, -OH, J - 7 Hz), 1.98 (quintet, 2H, J - 8 Hz), 2.39-2.52 - 309 -(m, 2H), 2.62-2.75 (m, 2H), 4.15 (d, 2H, -CH20H, J - 7 Hz). Exact Mass calcd. f o r C 6H 9OI (M+): 223.9700; found: 223.9700. Preparation of 2-bromomethyl-l-iodocyclopentene (325) To a c o l d (-20°C), s t i r r e d s o l u t i o n of triphenylphosphine (738 mg, 2.816 mmol) i n 11 mL of dry dichloromethane was added 145 A * L (2.82 mmol) of bromine u n t i l a pale yellow color p e r s i s t e d . Triphenylphosphine was added i n very small portions u n t i l the s o l u t i o n turned c l e a r . A s o l u t i o n of the iodo alcohol (324) (631 mg, 2.816 mmol) i n 5 mL of dry CH2CT2 was added dropwise over a period of 5 min. A f t e r the dropping funnel had been ri n s e d with 1.0 mL of dry CH2CI2, the re a c t i o n mixture was allowed to warm to room temperature. The s o l u t i o n was concentrated and petroleum ether (10 mL) was added to the residue. The res u l t a n t s l u r r y was passed through a short column of F l o r i s i l (5 g, e l u t i o n with petroleum ether). Concentration of the eluate, followed by d i s t i l l a t i o n ( a i r - b a t h temperature, 50-55°C/0.05 Torr) of the r e s i d u a l o i l afforded 648 mg (80%) of the iodo bromide (325). This c o l o r l e s s o i l exhibited i r ( f i l m ) : 1627, 1431, 1209, 920 cm - 1; lH nmr (300 MHz, CDCI3) 5: 2.02 (quintet, 2H, J - 8 Hz), 2.46-2.56 (m, 2H), 2.73 (broad t, 2H, J •= 8 Hz), 4.08 (s, 2H, -CH 2Br). Exact Mass calcd. f o r C 6 H g 7 9 B r I (M+): 285.8856; found: 285.8862. - 310 -Preparation of methyl 1-(2-iodo-l-cyclopentenvl)methyl-2-trimethyl- stannyl - 2 -cyclopentenecarboxylate (326) To a cold ( - 2 0 ° C ) , s t irred solution of lithium diisopropylamide (2.0 equiv) in 5 mL of dry THF was added the ester (205) (183 mg, 0.6182 mmol) as a solution in 3 mL of dry THF and the solution was s t i rred at -48°C for 20 min. HMPA (3 equiv) was added to the yellow solution and the mixture was s t irred at -48°C for 10 min. A solution of the iodo bromide (325) (192 mg, 0.666 mmol) in 2 mL of dry THF was added. The mixture was s t i rred at -48°C for 30 min, and then saturated aqueous ammonium chloride (-1 mL) was added and the solution was allowed to warm to room temperature. The organic solution was washed three times with saturated aqueous ammonium chloride, dried over anhydrous magnesium sulfate and concentrated. Flash column chromatography of the residual o i l on s i l i c a gel (20 g, elution with petroleum ether-diethyl ether; 17:1) and d i s t i l l a t i o n (air-bath temperature 1 6 0 - 1 6 5 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 194 mg (64%) of the ester (326). This colorless o i l exhibited i r (film): 1734, 1631, 1232, 1053, 771 cm' 1 ; 1 H nmr (400 MHz, CDC13) 6: 0.19 (s, 9H, -SnMe3, 2 J S n . H - 5 4 H z >- 1 - 7 9 < d d d -IH, H c , J - 13, 7, 6.5 Hz), 1.89 (quintet, 2H, Hp, J - 7.5 Hz), 2.08-2.24 (m, 2H, Hp), 2.27 (d, IH, H D , J - 14 Hz), 2.37 (ddd, IH, H c , J - 13, 7, 6.5 Hz), 2.51 (ddd, 2H, H f i , J - 7, 6.5, 2 Hz), 2.60-2.70 (m, - 311 -2H, H G ) , 2.90 (d, IH, H D , J - 14 Hz), 3.67 (2, 3H, -OMe), 5.99 (t, IH, H A , J - 2 Hz, 3J_Sn-H " 3 7 Hz). In a decoupling experiment irradiat ion of the signal at 6 2.37 simplif ied the signal at 6 1.79 to a dd (J - 7, 6.5 Hz) and simplif ied the signal at S 2.51 to a dd (J - 7, 2 Hz). Irradiat ion of the multiplet at 6 2.08-2.44 changed the signal at 1.89 to a broad t r i p l e t (J - 7.5 Hz). Irradiation of the signal at S 2.90 collapsed the doublet at 6 2.27 to a singlet . F inal ly irradiat ion of the signal at 6 5.99 simplified the signal at 2.51 to a dd (J - 7, 6.5 Hz). Exact Mass calcd. for C ^ H ^ C ^ I 1 1 ^ ( M ^ C ^ ) : 476.9684; found: 476.9676. Preparation of the t r i c y c l i c ester diene (327) Following general procedure 11, to a s t irred solution of the v iny l -stannane -v inyl iodide (326) (194 mg, 0.380 mmol) in 0.5 mL of dry acetonitr i le was added a solution of in s i tu generated palladium(O) in 3 mL of dry acetonitr i le , and the mixture was s t i rred at 80°C for 24 h. T ic and glc analysis of an aliquot, indicated the presence of one major component. Concentration, followed by column chromatography of the residual o i l on s i l i c a gel (10 g, elution with petroleum ether-diethyl ether; 17:1) and d i s t i l l a t i o n (air-bath temperature 7 0 - 7 5 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 53 mg (68%) of the diene (327). This - 312 -colorless o i l exhibited i r (film): 3055, 1728, 1650, 1614, 1202, 1162 c m - 1 ; X H nmr (400 MHz, C 6 D 6 ) 6: 1.77 (ddd, IH, J - 12, 9, 8.5 Hz), 1.91-2.08 (m, 4H), 2.12-2.33 (m, 3H), 2.41 (dd, IH, 1 - 1 2 , 6 Hz), 2.40-2.50 (m, IH), 2.98 (broad d, IH, b i s - a l l y l i c proton, J - 16 Hz), 3.00-3.11 (m, IH), 3.31 (s, 3H, -OMe), 5.33 (broad s, IH, o le f in ic proton). Exact Mass calcd. for C 1 3H 1 g0 2 (M+): 204.1150; found: 204.1148. Preparation of methyl 1-(2-iodo-l-cvclopentenvl)methyl-2-trimethyl- stannvl- 2-cvclohexenecarboxvlate (328) To a cold ( - 2 0 ° C ) , s t irred solution of lithium diisopropylamide (2.0 equiv) in 5 mL of dry THF was added the ester (206) (117 mg, 0.385 mmol) as a solution in 3 mL of dry THF and the solution was s t irred at -20°C for 5 min. HMPA (3 equiv) was added to the yellow solution and the mixture was s t i rred at -20°C for 30 min. A solution of the Iodo bromide (325) (146 mg, 0.507 mmol) in 2 mL of dry THF was added. The mixture was s t i r red at -20"C for 30 min and then saturated aqueous ammonium chloride (-1 mL) was added and the resultant mixture was allowed to warm to room temperature. The organic layer was washed three times with saturated aqueous ammonium chloride, dried over anhydrous magnesium - 313 -sulfate and concentrated. Flash column chromatography of the residual o i l on s i l i c a gel (15 g, elution with petroleum ether-diethyl ether; 17:1) and d i s t i l l a t i o n (air-bath temperature 1 6 5 - 1 7 0 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 129 mg (66%) of the ester (328). This colorless o i l exhibited i r (film): 1717, 1638, 1601, 1435, 1214, 1159, 768 cm"1; X H nmr (400 MHz, CDCI3) 6: 0.15 (s, 9H, -SnMe.3, 2 J S n - H - 52 Hz), 1.48-1.56 (t, IH), 1.64-1.76 (m, 2H), 1.90 (quintet, 2H, Hp, J — 7.5 Hz), 2.00-2.23 (m, 3H), 2.43 (d, IH, H D , J - 14 Hz), 2.66 (broad t, IH, J - 7.5 Hz), 2.69-2.77 (m, 2H), 2.80 (broad d, IH, H D , J - 14 Hz), 2.77-2.84 (m, IH), 3.68 (s, 3H, -OMe), 6.01 (t, IH, H A , J - 3.5 Hz, 3 J S n . H - 75 Hz). Exact Mass calcd. for C 1 6 H 2 40 2 ISn (M+'C^): 494.9845; found: 494.9838. Preparation of the t r i c y c l i c ester diene (329) C0 2Me Following general procedure 11, to a s t i rred solution of the v iny l -stannane -v inyl iodide (326) (100 mg, 0.196 mmol) in 0.5 mL of dry acetonitr i le was added a solution of in s i tu generated palladium(O) in 2 mL of dry acetonitri le and the mixture was s t i rred at 80°C for 21 h. Tic analysis of an aliquot indicated the presence of one product and a minor amount of starting material. Concentration, followed by column chromatography of the black o i l on s i l i c a gel (10 g, elution with - 314 -petroleum ether-diethyl ether; 17:1) and d i s t i l l a t i o n (air-bath tempera-ture 9 5 - 1 0 0 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 28 mg (70%) of the diene (329). A small amount (6 mg) of the starting material (326) was also recovered. Compound (329), a colorless o i l , exhibited i r (f i lm): 1725, 1448, 1197, 1162 cm' 1 ; X H nmr (400 MHz, C 6 D 6 ) 6: 1.45-1.54 (m, IH), 1.55-1.74 (m, 2H), 1.92-2.10 (m, 4H), 2.11-2.35 (m, 5H), 2.50 (dt, IH, J - 12, 3.5 Hz), 2.86 (d, IH, J - 16 Hz), 3.33 (s, 3H, -OMe), 5.35 (t, IH, v iny l proton, J - 3.5 Hz). Exact Mass calcd. for CiiFl302 (M+): 218.1307; found: 218.1310. Preparation of methyl 1-(2-iodo-l-cyclopentenyl)methyl-2-trimethyl- stannyl-2-cycloheptenecarboxylate (330) To a cold ( - 2 0 ° C ) , s t irred solution of lithium diisopropylamide (2.0 equiv) in 5 mL of dry THF was added the ester (207) (107 mg, 0.336 mmol) as a solution in 3 mL of dry THF. HMPA (3 equiv) was added and the solution was s t i rred at -48°C for 3 h. A solution of the iodo bromide (325) (101 mg, 0.3506 mmol) in 2 mL of dry THF was added dropwise over a period of 10 min. The mixture was s t irred at -48°C for 45 min and then saturated aqueous ammonium chloride (-1 mL) was added and the solution was allowed to warm to room temperature. The organic solution was - 315 -washed three times with saturated aqueous ammonium chloride, dried over anhydrous magnesium sulfate, and concentrated. Flash column chromatogra-phy of the residual o i l on s i l i c a gel (10 g, elution with petroleum ether-diethyl ether; 17:1) and d i s t i l l a t i o n (air-bath temperature 1 7 5 - 1 8 0 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 98.5 mg (56%) of the ester (330). This colorless o i l exhibited i r (film): 1718, 1628, 1435, 1214, 1162, 767 cm"1; ^ nmr (400 MHz, CDC13) 6: .0.15 (s, 9H, -SnMe3, 2 J S n _ H - 54 Hz), 1.22-1.35 (m, IH), 1.48-1.57 (m, 2H), 1.64-1.77 (m, 2H), 1.89 (quintet, 2H, Hp, J «= 7.5 Hz), 2.02-2.23 (m, 5H), 2.43 (d, IH, H D , £ - 1 4 Hz), 2.59-2.65 (m, 2H), 2.81 (d, IH, H D , J - 14 Hz), 3.68 (s, 3H, -OMe), 6.00 (t, IH, H A , J - 3.5 Hz, 3 J S n . H = 7 4 Hz). Exact Mass calcd. for C 1 7 H 2 6 0 2 I S n (M+-CH3): 509.0001; found: 508.9998. Preparation of the t r i c y c l i c ester diene (331) C02Me Following general procedure 11, to a s t irred solution of the v iny l -stannane -v inyl iodide (330) (22.5 mg, 0.0439 mmol) in 0.5 mL of dry acetonitr i le was added a solution of in s i tu generated palladium(O) in 2 mL of dry acetonitri le and the mixture was s t i rred at 85°C for 4 h. Tic analysis of an aliquot indicated the presence of one major compo-nent. Concentration, followed by column chromatography of the residual o i l on s i l i c a gel (2 g, elution with petroleum ether-diethyl ether; 316 -17:1) and d i s t i l l a t i o n (air-bath temperature 8 3 - 8 7 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 8.2 mg (80%) of the diene (331). This colorless o i l exhibited i r (film): 1728, 1655, 1444, 1230, 1198, 1169 cm* 1; X H nmr (400 MHz, C 6 D 6 ) 6: 1.30-1.42 (m, IH), 1.57-1.90 (m, 4H), 1.98-2.23 (m, 7H) , 2.24-2.39 (m, 3H), 2.83 (broad d, IH, J - 17 Hz), 3.40 (s, 3H, -OMe), 5.63 (dd, IH, v iny l proton, J - 9, 4.5 Hz). Exact  Mass calcd. for C 1 5H 2o02 : 232.1464; found: 232.1465. Preparation of compound (143) To a s t i rred solution of methyl (Z)-2,3-bis(trimethylstannyl)-8-bromo-2,8-nonadienoate (134) (48.6 mg, 0.084 mmol) in 1 mL of dry THF was added (PPt^^Pd (5.1 mg, 0.004 mmol) and the mixture was s t irred at approximately 50°C for 24 h. Concentration, followed by column chromatography of the resultant brown o i l on s i l i c a gel (10 g, elution with petroleum ether-diethyl ether; 9:1) and d i s t i l l a t i o n (air-bath temperature 1 0 2 - 1 0 5 ° C / 0 . 0 5 Torr) of the o i l thus obtained, afforded 10 mg (36%) of the diene (143). This colorless o i l exhibited i r (film): 1710, 1635, 1605, 1193 (br), 774 cm* 1; X H nmr (270 MHz, CDC13) 6: 0.16 (s, 9H, -SnMe3, 2 J _ S n _ H = 56 Hz), 1.73-1.86 (m, 4H), 2.20-2.30 (m, 2H, v i n y l i c protons), 2.36-2.43 (m, 2H, v iny l i c protons), 3.68 (s, 3H, - 317 --OMe), 4.71-4.73 (m, IH, Hg), 4.78-4.81 (m, IH, H A ) . In a nOe difference experiment, irradiat ion of the singlet at 6 3.68 (-OMe) enhanced the signal at 6 0.16 (-SnMe.3), while irradiat ion of the signal at 6 0.16 (-SnMe3) enhanced the signals at 5 3.68 (-OMe) and S 4.78-4.81 (H A ) . Exact Mass calcd. for C 1 2 H 1 9 0 2 S n (M+'CT^): 315.0437; found: 315.0422. - 318 -REFERENCES 1. M. Pereyre, J . P . Quintard, and A. Rahm, Tin in Organic Synthesis, Butterworth and Co. L t d . , U . K . , 1987, p. 127-259. 2. J . K . S t i l l e , Angew. Chem. Int. Ed. Engl . , 25, 508-524 (1986). 3. D. Seyferth and M.A. Weiner, Chem. Ind. (London), 402 (1959). 4. (a) T.N. Mitchel l , J . Organomet. Chem., 304, 1 (1986). 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