UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

Reaction of (trialkylstannyl) copper reagents with acetylenic compounds Chong, John Michael 1983

Your browser doesn't seem to have a PDF viewer, please download the PDF to view this item.

Item Metadata

Download

Media
831-UBC_1983_A1 C56.pdf [ 10.61MB ]
Metadata
JSON: 831-1.0060687.json
JSON-LD: 831-1.0060687-ld.json
RDF/XML (Pretty): 831-1.0060687-rdf.xml
RDF/JSON: 831-1.0060687-rdf.json
Turtle: 831-1.0060687-turtle.txt
N-Triples: 831-1.0060687-rdf-ntriples.txt
Original Record: 831-1.0060687-source.json
Full Text
831-1.0060687-fulltext.txt
Citation
831-1.0060687.ris

Full Text

REACTION OF (TRIALKYLSTANNYL)COPPER REAGENTS WITH ACETYLENIC COMPOUNDS by JOHN MICHAEL CHONG Sc. (Hons.), University of B r i t i s h Columbia, 197 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 t h i s thesis as conforming to the required standard THE UNIVERSITY OF BRITISH COLUMBIA October 1983 ® John Michael Chong In p r e s e n t i n g t h i s t h e s i s i n p a r t i a l f u l f i l m e n t o f the reguirements f o r an advanced degree a t the U n i v e r s i t y o f B r i t i s h Columbia, I agree t h a t the L i b r a r y s h a l l make i t f r e e l y a v a i l a b l e f o r r e f e r e n c e and study. I f u r t h e r agree t h a t p e r m i s s i o n f o r e x t e n s i v e copying o f t h i s t h e s i s f o r s c h o l a r l y purposes may be granted by the head o f my department o r by h i s or her r e p r e s e n t a t i v e s . I t i s understood t h a t copying or p u b l i c a t i o n of t h i s t h e s i s f o r f i n a n c i a l g a i n s h a l l not be allowed without my w r i t t e n p e r m i s s i o n . Department o f (^LAjZ^/TUjdfV The U n i v e r s i t y of B r i t i s h Columbia 1956 Main Mall Vancouver, Canada V6T 1Y3 Date DE-6 (3/81) A B S T R A C T The reaction of a number of ( t r i a l k y l s t a n n y l ) c o p p e r reagents with 2-alkynoates, N,N-dimethyl-2-alkynaraides and 1-alkynes i s described. It has been found that the (trimethylstannyl)copper reagents _14_ and 43-46 e f f i c i e n t l y transfer the trimethylstannyl group to oc-alkynoates. Reagent 1_4 (THF, -48°C) provided predominantly the (Z)-3-trimethyl-stannyl-2-alkenoate (22), reagents 44_ and 45_ (THF, -48°C) afforded e s s e n t i a l l y e x c l u s i v e l y the corresponding (E) isomer 2_1_, while reagents 43 and 46_ gave a mixture of isomers. Using the above methodology, ethyl 2-pentynoate was converted into either (Z)- or (E_)-3-( tri-_n-butylstannyl)-2-pentenoate. The (E) isomer was converted into the vinylstannane 188 which was transformed (MeLi, THF, -20°C) into the corresponding stereochemically homogeneous v i n y l l i t h i u m reagent and elaborated into the acyl portion of (±)-triophamine (172), a diacylguanidine recently i s o l a t e d from Triopha  cat a l i n a e. Reaction of 2-alkynoates with excess 44 or 45 (THF, 0°C) afforded, as e s s e n t i a l l y the only products, (E_)-2,3-bis( t r i m e t h y l -stannyl)-2-alkenoates (115). One member of th i s new class of compounds, ester 114 (=115, R = Me, R' = Et) was s e l e c t i v e l y transmetalated (MeLi, THF, -98°C) and the resultant n u c l e o p h i l i c species was allowed to react with a number of reactive e l e c t r o p h i l e s to produce esters of general structure 141. - i i i -The reaction of to-halo-a, B-unsaturated esters (149; n = 3, 4; X = Br, I) with reagent _44 at low temperatures (THF, -78°C) afforded the expected (|0-3-triraethylstannyl-2-alkenoate while reaction with reagent 14 gave predominantly (= 95% s t e r e o s e l e c t i v i t y ) the expected (Z) isomer. Reaction with reagent \A_ at higher temperatures (THF-HMPA, -48°C to room temperature) afforded the ester 164 when n = 3, but gave the unexpected product 168 when n = 4. Upon reaction with N,N-dimethyl-2-alkynamides, reagents _14_ and 44_ both afforded excl u s i v e l y the (E) isomer 213 at low temperatures (THF, -78°C or -48°C). The addition of ether and higher reaction temperatures (0°C) with reagent permitted the preparation of the (Z) isomer 214 (= 95% s t e r e o s e l e c t i v i t y ) . The intermediate formed i n the reaction with reagent 44, was trapped with reactive a l k y l halides to produce amides of general structure 224. F i n a l l y , the reaction of 1-alkynes with reagent 44_ was i n v e s t i -gated. Under normal reaction conditions (THF, -63°C, 6 h), the reactions proceeded to only = 60% completion. However, the reactions proceeded e s s e n t i a l l y to completion when car r i e d out i n the presence of excess methanol (60 equiv.). The major product formed was the expected 2-trimethylstannyl-l-alkene (- 90% r e g i o s e l e c t i v i t y ) . - iv -[Me3SnCuSnMe,]Li 4 3 Me,SnCu-SMe2 4 4 [Me,SnCuCEC-CMe2OMe]Li 4 5 [Me,SnCuCN]Li 4 6 - v -TABLE OF CONTESTS Page ABSTRACT i i TABLE OF CONTENTS v LIST OF TABLES v i i i LIST OF GENERAL PROCEDURES i x LIST OF ABBREVIATIONS x i ACKNOWLEDGEMENTS x i i INTRODUCTION 1 I. General • 1 I I . Previous Work 4 II I . Proposals 10 DISCUSSION 14 I. Reaction of (Trimethylstannyl)copper Reagents with a, B-Acetylenic Esters 14 A. Preparation of (trimethylstannyDcopper reagents.... • 14 B. Preparation of a, B-acetylenic esters 17 C. Addition of (trimethylstannyl)copper reagents to a, p-acetylenic esters 20 D. Synthesis and transmetalation of a l k y l (E_)-2,3-bis-(trimethylstannyl)-2-alkenoates 36 E. Reaction of (trimethylstannyDcopper reagents with (jj-halo-a, p-acetylenic esters. I n t r a -molecular a l k y l a t i o n s 53 I I . Synthesis of the Acyl Portion of Triophamine 62 A. Introduction 62 - v i -B. Preparation of (Z)- and (E)-2,4-diethyl-4-hexenoic acid 64 C. Preparation of (±)-triophamine and i t s . diastereomer 69 I I I . Reaction of (Triraethylstannyl)copper Reagents with a, 8-Acetylenic N,N-Dimethylamides 70 A. Preparation of a, (3-acetylenic N,N-dimethyl-amides 70 B. Preparation of (Z)- and (E_)-N,N-diraethyl-3-t rime thyls tannyl-2-alkenamides 72 C. Trapping of the intermediate with e l e c t r o p h i l e s other than proton 85 D. Reactions of p-triraethylstannyl-a,8-unsaturated N,N-dimethylamides. 93 IV. Addition of (Trimethylstannyl)copper to 1-Alkynes: Synthesis of co-Substituted 2-Trimethylstannyl-1-alkenes 101 A. Introduction 101 B. Reaction of (trimethylstannyl)copper with 1-alkynes 106 EXPERIMENTAL 122 I. General 122 I I . Solvents and Reagents......... 124 I I I . Preparation of (Trialkylstannyl)copper Reagents.... 127 IV. Reaction of (Trimethylstannyl)copper Reagents with a, 8-Acetylenic Esters 131 A. Preparation of a, B-acetylenic esters 131 B. Reaction of ethyl 2-butynoate with ( t r i m e t h y l -stannyl) copper reagents 145 C. Preparation of a l k y l (E)- and (Z)-3-trimethyl-stannyl-2-alkenoates 149 - v i i -Page D. Synthesis and transmetalation of a l k y l (E)-2,3-bis(triraethylstannyl)-2-alkenoates 161 E. Preparation of co-substituted a, 6-acetylenic esters and reaction with (trimethylstannyl)-copper reagents... 182 V. Synthesis of the Acyl Portion of Triophamine 197 VI. Reaction of N,N-Dimethyl-2-alkynamides with (Trimethylstannyl)copper Reagents 211 A. Preparation of N,N-dimethyl-2-alkynamides. 211 B. Preparation of (E)- and (Z)-N,N-dimethyl-3-trimethylstannyl-2-alkenamides 217 C. Trapping of the intermediate with e l e c t r o p h i l e s other than proton 230 VII. Preparation of co-Substituted 2-Trimethylstannyl-1-alkenes 243 REFERENCES 261 - v i i i -LIST OF TABLES Page Table I Preparation of a,8-acetylenic esters from 1-alkynes 18 Table II Reaction of ethyl 2-butynoate with various (trimethylstannyDcopper reagents..... 21 Table I II Conversion of a,8-acetylenic esters into (Z)-and (E_)-3-trimethylstannyl-2-alkenoates 28 Table IV Preparation of (E_)-a, 8-bis( trimethylstannyl)-oc, 8-unsaturated esters 40 Table V *H nmr chemical s h i f t s of Y ~ P r o t o n s °f esters 21, 22 and 115 41 Table VI Transmetalation of ethyl (E_)-2,3-bis-(trimethylstannyl)-2-butenoate and reaction of the intermediate anion with e l e c t r o p h i l e s 48 Table VII Preparation of a,8-acetylenic N,N-dimethylamides 71 Table VIII Reaction of li t h i u m (phenylthio)(trimethyl-stannyDcuprate with a, 8-acetylenic N,N-dimethylamides 80 Table IX Reaction of (trimethylstannyl)copper with a, 8-acetylenic N,N-dimethylamides. 83 Table X Trapping of the intermediate derived from addition of (trimethylstannyl)copper to a,8-acetylenic N,N-dimethylamides with e l e c t r o p h i l e s 87 Table XI Addition of (trimethylstannyl)copper to 1-alkynes 115 Table XII P u r i f i c a t i o n of solvents and reagents 125 - i x -LIST OF GENERAL PROCEDURES Page Procedure A Preparation of a,8-Acetylenic Esters.... 131 Procedure B Reaction of Ethyl 2-Butynoate with (Trimethyl-stannyl) copper Reagents 145 Procedure C Preparation of A l k y l (E_)-3-Trimethylstannyl-2-alkenoates. Reaction of (TrimethylstannyD-copper with a,8-Acetylenic Esters 149 Procedure D Preparation of A l k y l (Z)-3-Trimethylstannyl-2-alkenoates. Reaction of Lithium Phenylthio-(triraethylstannyl)cuprate with a,B-Acetylenic Esters under "Thermodynamic Conditions"........ 150 Procedure E Preparation of A l k y l (E)-2,3-Bis(trimethyl-stannyl)-2-alkenoates. Reaction of a, 8-Acetylenic Esters with Excess (Trimethyl-stannyDcopper 161 Procedure F Preparation of A l k y l (E_)-2,3-Bis( t r i m e t h y l -stannyl)-2-alkenoates. Reaction of a, 8-Acetylenic Esters with Excess Lithium (3-Methoxy-3-methyl-l-butynyl)(trimethylstannyl)-cuprate 162 Procedure G Transraetalation of E t h y l (E)-2,3-Bis(trimethyl-stannyl)-2-butenoate and Reaction of the Anion with E l e c t r o p h i l e s 175 Procedure H Preparation a,8-Acetylenic N,N-Dimethylamides.. 211 Procedure I Preparation of (E_)-N,N-DIraethyl-3-triraethyl-stannyl-2-alkenamides. Reaction of N,N-Dimethyl-2-alkynamides with Lithium Phenylthio-(trimethylstannyDcuprate i n THF 217 Procedure J Addition of (Trimethylstannyl)copper to N,N-Dimethyl-2-alkynamides 218 Procedure K Preparation of (Z)-N,N-Dimethyl-3-triraethyl-stannyl-2-alkenamides. Reaction of N,N-Diraethyl-2-alkynamides with Lithium Phenylthio-(trimethylstannyl)cuprate under "Thermodynamic Conditions" 219 - x -Page Procedure L Reaction of the Intermediate formed by Addition of Lithium Cyano(trimethylstannyl)cuprate to N,N-Dimethyl-2-butynamide with Carbon E l e c t r o p h i l e s 230 Procedure M Reaction of the Intermediate formed by Addition of (Trimethylstannyl)copper to N,N-Dimethyl-2-alkynamides with Carbon E l e c t r o p h i l e s 231 Procedure N Addition of (Trimethylstannyl)copper to 1-Alkynes in the Presence of Methanol. Preparation of 2-Trimethylstannyl-l-alkenes.... 244 - x i -LIST OF ABBREVIATIONS The following abbreviations have been used throughout this thesis: DCC = N,N-dicyclohexylcarbodiimide DIBAL = diisobutylalurainum hydride DME = dimethoxyethane DMF = N,N-dimethylforraamide DMSO = dimethyl sulfoxide EDA = ethylenediamine equiv. = equivalents glc = gas-liquid chromatography HMPA = hexamethylphosphoramide nmr = proton nuclear magnetic resonance i r = infrared LAH = lithium aluminum hydride LDA = lithium diisopropylamide LiTMP = lithium 2,2,6,6-tetraraethylpiperidide PPTS = pyridinium _p-toluenesulfonate pyr = pyridine rt = room temperature THF = tetrahydrofuran THP = tetrahydropyranyl t i c = thin-layer chromatography TMEDA = N,N,N',N'-tetramethylethylenediamine - x i i -ACKNOWLEDGEMENTS I would l i k e to thank Professor Ed Piers for his understanding guidance and encouragement throughout the course of th i s work. It has been a t r u l y rewarding experience working with someone who just doesn't understand but does. I would also l i k e to thank the assorted dogs, nightingales, swans, and other strays who have inhabited Rooms 400 and 402 and, by th e i r presence, made these laboratories a pleasurable place i n which to work. The amazing proof-reading talents and e f f o r t s of M.E. Alderdice are g r a t e f u l l y acknowledged as i s the assistance of R.J. Armstrong i n various aspects of the preparation of th i s t h e s i s . F i n a l l y , I am indebted to the Natural Sciences and Engineering Research Council of Canada for f i n a n c i a l support. INTRODUCTION I. General About forty years ago, Gilman and his co-workers 1 showed that the reaction of tetraphenyltin with excess n-butyllithium could be used to prepare t e t r a - n - b u t y l t i n (equation 1). Since that time, this type of Ph«Sn + 4n-BuLi Q-B^Sn + 4 PhLi (1) reaction, the exchange of organic groups between an organolithium reagent and an organostannane (or an organic de r i v a t i v e of other heavy metals such as mercury, thallium, and lead), has been developed into a valuable tool for organic synthesis. The primary focus on t h i s type of reaction, now commonly referred to as a transraetalation, has been for the preparation of organolithium compounds which are not r e a d i l y accessible v i a other routes; these organolithium compounds may be coupled with a wide variety of e l e c t r o p h i l i c moieties i n the synthesis of complex substances, including natural products. It was some twenty years a f t e r Gilman's o r i g i n a l report that the synthetic u t i l i t y of th i s reaction was demonstrated. In 1959, Seyferth 2 and Weiner reported the preparation of v i n y l l i t h i u m , inaccessible u n t i l then, by reaction of phenyllithiura with t e t r a v i n y l t i n (equation 2). (CHa=CH)4Sn + 4 PhLi 4 CH,=CHLi + Ph«Sn (2) - 2 -U n t i l then, only compounds rea d i l y prepared by other means had been synthesized using this method. In an important series of reports, Seyferth and his co-workers also studied the preparation of a l l y l - and 3 4 5 raethallyl- , cyclopropyl- , propenyl- and isopropenyl- , and benzyl-l i t h i u m 6 . From these "simple" beginnings, a number of more highly function-a l i z e d vinylstannanes have been prepared and used i n organic syntheses. Several c h a r a c t e r i s t i c s of the transmetalation reaction make i t p a r t i c u l a r l y a t t r a c t i v e : (a) The reaction usually proceeds e f f i c i e n t l y at low temperatures, often below -50°C, (b) the reaction i s completely s t e r e o s p e c i f i c , and (c) the by-product of the reaction i s a coordin-a t i v e l y saturated compound (e.g. tetramethyltin) which does not usually i n t e r f e r e with reactions of the l i t h i a t e d product. The following examples are representative of the use of this type of reaction. Corey and Wollenberg' 7, i n one of the f i r s t reports of the use of a functionalized vinylstannane, showed that the vinylstannane 2_ could be r e a d i l y prepared by hydrost anna t ion of the terminal acetylene J_.~ Transmetalation of 2_ and conversion of the r e s u l t i n g l i t h i o species into the corresponding cuprate allowed the ready conjugate addition of a protected (E_)-3-hydroxypropenyl group to an a,8-unsaturated ketone (Scheme 1). A s i m i l a r approach has been used i n prostaglandin syntheses (Scheme 2). Thus, the acetylene k_ was converted into the vinylstannane 5_ v i a hydrostannation. Transmetalation of 5, followed by cuprate - 3 -H-C=C-CH20THP 1 Q-Bu,SnH AIBN.A D-Bu,Sn 1) n-BuLi 2) Q-Pr-CSC-Cu • o * OTHP OTHP S cheme 1 formation, reaction with the highly functionalized cyclopentenone 6_, and hydrolysis, afforded (±)-prostaglandin E 2 (7_) and (±)-15-epi-prostaglandin E 2 (8). An extensive l i s t of recent examples of v i n y l l i t h i u r a reagents 9 avai l a b l e v i a transraetalation of vinylstannanes has been published . It should be noted that the most common route for the preparation of vinylstannanes involves the hydrostannation of an acetylenic compound. Since t h i s reaction often leads to mixtures of p r o d u c t s 1 0 ' 1 1 and has been known to give inconsistent r e s u l t s , other more regio- and stereoselective methods for the preparation of vinylstannanes would enhance th e i r usefulness. - 4 -S cheme 2 II. Previous Work Our I n i t i a l interest in this area arose from a desire to develop B-acylvinyl anion equivalents. Previous work in our laboratories had shown that B-bromo- and p-iodo-a,p-unsaturated ketones (9_) are excellent 13 14 synthetic equivalents of p-acylvinyl cations (10) » - 5 -Thus, the reaction of p-halo enones (9 ) with a variety of n u c l e o p h i l i c reagents, such as alkylcuprates, afforded 8-substituted enones (11) i n which the o r i g i n a l halide has been replaced by a n u c l e o p h i l i c species (equation 3). C l e a r l y , development of a method of reversing the mode of r e a c t i v i t y (umpolung) of these 8-halo enones would extend t h e i r synthetic u t i l i t y . In other words, i f compounds 9_ could somehow be derivatized so that reaction with e l e c t r o p h i l e s (E +) was also possible, enones J ^ , i n which the o r i g i n a l halide has been replaced by an e l e c t r o p h i l i c species, could also be prepared (equation 4). In work directed towards transforming these 8-halo enones into derivatives suitable for use as 8 - a c y l v i n y l anions, i t was found that t h i s could be suc c e s s f u l l y achieved v i a 8 - t r i a l k y l s t a n n y l - a , 8 -15 unsaturated ketones (Scheme 3). For example, 3-iodo-2-cyclohexen-l-one (13) reacted smoothly with lithium (phenylthio)(triraethylstannyl)-cuprate (14) 1 6, a new reagent developed for th i s transformation, to produce 3-trimethylstannyl-2-cyclohexen-l-one (15) i n excellent y i e l d . This material was converted into the s i l y l enol ether 16_ which underwent transmetalation to produce the v i n y l l i t h i u m species 17. The l a t t e r - 6 -reagent, which i s a B-acylvinyl anion equivalent, reacted with a number of e l e c t r o p h i l e s to a f f o r d dienes _18_ which were hydrolyzed to the 8-substituted enones 19. This new technology was thus u s e f u l l y complementary to the e a r l i e r work involving n u c l e o p h i l i c additions to 8-halo enones. Other workers have since used s i m i l a r methodology for 17 the preparation of substituted 2-cyclopenten-l-ones . Further work showed that the addition of the cuprate reagent J^ 4_ to a,B-acetylenic esters (20) could be controlled experimentally so as to produce, highly s t e r e o s e l e c t i v e l y , either of the isomeric (E_)- or 18 (_Z)-8-trimethylstannyl-a, B-unsaturated esters 7A_ and 22_, r e s p e c t i v e l y . Thus, when the reaction was carried out at low temperatures (-78°C) i n the presence of a proton source (methanol) the major (>98% - 7 -13 17 18 [Me,SnCuSPh]Li 14 MeLi HCI SnMe, 15 1) LDA 2) t-BuMe2SiCI OSi - f SnMe, 16 19 S cheme 3 s t e r e o s e l e c t i v i t y ) product was the (E) ester 21_, while the (Z) ester 22 was the major (> 96% s t e r e o s e l e c t i v i t y ) product obtained a f t e r - 8 -h y d r o l y s i s when the r e a c t i o n was performed at h igher (-48°C) temperatures i n the absence of a proton source (Scheme 4 ) . Scheme 4 Conce ivab ly , these l a t t e r m a t e r i a l s could be r e a d i l y converted i n t o reagents of genera l s t r u c t u r e s 23_ and 24_ which correspond to the 1 9 genera l g eomet r i c a l l y i s omer i c synthons 25_ and 26_, r e s p e c t i v e l y (Scheme 5 ) . React ion of the reagents 23_ and 24_ w i t h e l e c t r o p h i l e s would then a f f o r d the products 27 and 28. In f a c t , two of the unsaturated e s t e r s , 29_ and 30, were f u r t h e r transformed i n t o the geomet r i c a l l y i somer i c 4 - l i t h i o - l , 3 - p e n t a d i e n e s 31_ and 32, r e s p e c t i v e l y (Scheme 6 ) . The l a t t e r i n te rmed ia tes reacted smoothly w i t h e l e c t r o p h i l e s to give s u b s t i t u t e d dienes of genera l s t r u c t u r e s 33 and 34. - 9 -W = group derived from the ester function S cheme 5 - 10 -S cheme 6 I I I . P roposa l s C l e a r l y , the cuprate _14_ i s a useful reagent for the stereo-s e l e c t i v e transfer of the trimethylstannyl group to a-alkynoates. Furthermore, there i s considerable promise i n the conversion of the products 21 and 22_ into stereochemically well-defined v i n y l l i t h i u r a reagents, and many extensions of the work described above may be envisaged. We were i n t e r e s t e d i n expanding i n a number of ways the methodology described above. For example, we were i n t e r e s t e d i n forming other ( t r i m e t h y l s t a n n y l ) c o p p e r reagents and i n i n v e s t i g a t i n g t h e i r r e a c t i v i t y w i t h a,8-acetylenic e s t e r s and other s u b s t r a t e s . It i s well-known with alkylcopper reagents that the nature and stoichioraetry of a u x i l a r y ligands have a s i g n i f i c a n t e f f e c t on the r e a c t i v i t y of the reagents ; we wished to a s c e r t a i n whether or not d i f f e r e n t ( t r i m e t h y l -stannyl) copper reagents e x h i b i t s i m i l a r r e a c t i v i t y patterns or behave much l i k e the (phenylthio)cuprate 14. Also, the p o s s i b i l i t y of t r a p p i n g , with e l e c t r o p h i l e s (Y +) other than proton, the intermediates formed i n the a d d i t i o n s of ( t r i m e t h y l -stannyDcopper reagents to a,8-acetylenic e s t e r s , to produce est e r s of general s t r u c t u r e s 35_ and _36_, was an i n t r i g u i n g thought (Scheme 7). Although the s t r u c t u r e s of the intermediates are unknown, trapping at low temperature (-78°C) would presumably a f f o r d e s t e r 35_ while trapping at higher temperatures (>-48°C) would be expected to a f f o r d the geometric isomer J36_ i n analogy with formation of the protonated e s t e r s 21 and 22. If s u c c e s s f u l , t h i s would be a ready entry i n t o h i g h l y s u b s t i t u t e d stereocheraically homogeneous v i n y l l i t h i u m reagents such as 37 and _38 which correspond to the donor synthons 39_ and 40, r e s p e c t i v e l y . Reaction of these reagents w i t h e l e c t r o p h i l e s (E +) would a f f o r d o l e f i n s 41_ and 42_ i n which the r e l a t i v e p o s i t i o n s of the s u b s t i t u e n t s on the carbon-carbon double bond are w e l l - d e f i n e d . R-C5C-C0.R' 20 1) [Me,SnCuZ]Li 2) Y + H R W 39 Me.Sn^ Y R CO,R' 35 J I 37 "X' R W 41 Me,Sn C02R' 36 J I X 38 X 42 w X R Y 40 W= group derived from the ester function Scheme 7 Another p o s s i b i l i t y was to invest i gate the add i t ion of ( t r i -methylstannyDcopper reagents to a ,8 - ace ty len i c amides. a , 8-Acetylenic a m i d e s 2 0 ' 2 1 react d i f f e r e n t l y from a ,8 - ace ty len i c esters with organo-- 13 -copper reagents. We were interested i n determining what differences exist i n the reactions of various (trimethylstannyl)copper reagents with these amides and also i n comparing the reactions of these amides with the corresponding reactions of a , 8 - a c e t y l e n i c esters. - 14 -DISCUSSION I. Reaction of (Trimethylstannyl)copper Reagents with  g, 8-Acetylenic Esters A. Preparation of (trlmethylstannyl)copper reagents In order to study the r e a c t i o n of va r ious ( t r i m e t h y l s t a n n y l ) -copper reagents w i th oc-alkynoates and other s ub s t r a te s , the reagents 14, 43-46* were prepared. [Me,SnCuSPh]U 14 [Me,SnCuSnMe,]U 4 3 Me,SnCu-SMe, 4 4 ^e,SnCuCSC-CMetOMe]Li 4 5 [Me,SnCuCN]Li 4 6 The reagents 43-46 were prepared i n a manner analogous to that p r e v i ou s l y reported f o r the p repa ra t i on of the (pheny l t h i o ) cup ra te 1 4 1 6 , * These f o rmu la t i on s , and those of other copper reagents and i n t e rmed i a t e s , are not meant to imply a c t u a l s t r u c t u r e s , but are used to show s to i ch i omet r y and f o r convenience. - 15 -which involved the addition of s o l i d (phenylthio)copper to a cold 23 (-20°C) tetrahydrofuran solution of (t r i m e t h y l s t a n n y l ) l i t h i u m (equation 5). The reagents 43_ and 44_ have also been reported Me,SnLi + PhSCu *• [Me,SnCuSPh]Li < 5) 14 p r e v i o u s l y 2 4 . Addition of cuprous bromide-dimethyl s u l f i d e complex 2 5 (0.5 equiv.) to a cold (-78°C) THF solution of Me3SnLi afforded the dark red cuprate reagent 43 (equation 6); use of one equivalent of CuBr#SMe2 gave the dark red copper reagent 44_ » (equation 7). 2Me,SnLi + CuBr-SMe 4 |Me,SnCuSnMe,]U + LiBr (6) 4 3 Me,SnLi + CuBr -SMe , MejSnCu-SMe, + LiBr ( 7 ) 4 4 Lithium (3-methoxy-3-methyl-l-butynyl)(trimethylstannyl)cuprate 28 (45) was prepared s i m i l a r l y from the corresponding alkynylcopper and Me3SnLi (equation 8) as a dark red solution i n THF. Me,SnLJ + C u C S C - C M e , O M e p«le,SnCuCSC-CMe20Me]U ( 8 ) 4 5 F i n a l l y , we found that a bright orange solution of li t h i u m (cyano)(trimethylstannyl)cuprate (46) could be conveniently prepared - 16 -from CuCN 2 9 and Me3SnLi (equation 9 ) . Me,SnLi + CuCN [Me,SnCuCNJLi (9) 46 With respect to the preparation of these reagents, i t i s pertinent to point out a number of important d e t a i l s . As with most alkylcuprates, these (trimethylstannyl)copper reagents are thermally unstable, so i t i s imperative to maintain appropriate reaction temperatures. In t h i s regard, although a thorough study was not done, observations made during the course of this work indicate that the order of thermal s t a b i l i t y of these reagents i s : the (phenylthio)cuprate _14 > the (cyano)cuprate 46_ > the bis(trimethylstannyl)cuprate 43_ = the copper reagent jt4_ = the (alkynyl) cuprate 45. Also, these reagents are 2 5 s e n s i t i v e to oxygen and to traces of other t r a n s i t i o n metals a ; thus i t i s important to maintain s t r i n g e n t l y clean oxygen-free reaction conditions. Related to the l a t t e r point, i t i s best to use f r e s h l y prepared, white CuBr»SMe 2 which i s free of Cu(II) (the presence of which i s indicated by a red-brown color) for the preparation of reagents 43_ and 44. For the preparation of the (phenylthio)cuprate _14_, we have found that, although (phenylthio)copper remains a uniform yellow color even af t e r storage (ambient temperature, under argon) for years, the cuprate \k_ did not consistently form when the (phenylthio)copper was more than - 6 months old. It i s best, therefore, to use r e l a t i v e l y fresh PhSCu. In a similar vein, the reagent 45_ should be prepared within a few days of forming the corresponding alkynylcopper s a l t . In - 17 -the case of the (cyano)cuprate ^6_, p u r i f i c a t i o n of commercial CuCN i s unnecessary D as the Cu(I) form i s more stable than the Cu(II) form. F i n a l l y , i t should be noted that the methyllithium used to form Me3SnLi should be from a r e l a t i v e l y freshly-opened bottle; for unknown reasons, the cuprate reagents did not always form when bottles of methyllithium which had been opened and stored at 4°C for more than = 6 months were used. B. Preparation of a,8-acetylenic esters The r e q u i s i t e a,B-acetylenic esters were prepared via known methods. In general, these materials were prepared by reaction of an a l k y n y l l i t h i u m with methyl or ethyl chloroformate (equation 12). The required a l k y n y l l i t h i u m species were, in turn, generated either by q A deprotonation of a 1-alkyne with methyllithium (equation 10) or by reaction of a 1,1-dibromo o l e f i n with m e t h y l l i t h i u m 3 1 (equation 11). A summary of the preparation of a number of a,8-acetylenic esters from the corresponding 1-alkynes i s given i n Table I. R - C S C - H 4 7 MeLi R - C S C - L i 4 8 C H 4 (10) R-CH=CBr2 + 2 Me Li • R - C S C - L i + C H 4 + CH,Br + LiBr (11) 4 9 4 8 R-C=C-Li 4 8 + CI-COaR' R-CEC-CO.R' + LiCI 20 (12) - 18 -Table I. Preparation of a, 8-acetylenic esters from 1-alkynes. 1) Me Li R-C5C-H R - C S C - C O . R 1 47 2) C I - C O A R ' 2 0 Entry l-Alkyne R R' Ester Y i e l d (%) a 1 50 Me Et 51_ 87 2 52 Et Et _53 90 3 54 _t-BuMe2Si0CH2 Et 55_ 83 4 56 2-(2-cyclopentenyl)ethyl Me 57 82 5 58 (3-cyclohexenyl)methyl Me 59 77 6 60 n-hexyl Me 6J_ 88 a Y i e l d of Isolated, p u r i f i e d product. - 1 9 -The 1-alkynes (47) used to prepare the esters 20_ shown i n Table I 3 2 are mostly commercially available (entries 1,2,6) or known (entry 3) compounds. Alkynes 56_ and _58_ (entries 4,5) were prepared by reaction of the corresponding bromide with lithium acetylenide-ethylenediamine complex 3 3 (equations 13,14). Ph,P-Br, Li-CBC-H-EDA H.-CSC-H 6 2 6 3 5 6 ( 1 3 ) ^ ^ Ph.P-Br, ^ ^ U-CSC-H-EDA c r - — - c r * — - cr z 6 4 6 5 5 8 1,1-Dibromo o l e f i n s , available by reaction of aldehydes with a carbon tetrabromide-triphenylphosphine reagent 3 1, were also used as precursors to a,3-acetylenic esters. For example, treatment of c y c l o -propanecarboxaldehyde (66) 3 I + with carbon tetrabromide-triphenylphosphine afforded the dibromo o l e f i n 67_ which, upon successive treatment with methyllithium (2 equiv.) and methyl chloroforraate, provided methyl cyclopropylpropynoate (68) (equation 15). In an e s s e n t i a l l y i d e n t i c a l manner, isobutyraldehyde (69) was converted into the a,B-acetylenic ester 71_ (equation 16). Ph,P-CBr« B f >V^ 8 r 1 > II c -Pr -C3C -C0 2 Me (15) 2) CICO.Me 6 6 6 7 6 8 - 20 -Ph,P-CBr4 Br 1) MeLi i -Pr-C£C-C0 2 Me (16) H 2) CICOaMe 69 70 71 C. Addition of (trimethylstannyl)copper reagents to  g,B-acetylenlc esters 1 8 Since previous work i n our laboratory had already established the stereochemical outcome of the reaction of the (phenylthio)cuprate J_4_ with ethyl 2-butynoate (51) under a v a r i e t y of conditions, we decided to investigate the reactions of the cuprate reagents 43-46 with t h i s ester. Some of the results obtained are summarized in Table I I . From the Table, i t can be seen that only the (phenylthio)cuprate reagent 1_4_ gave s y n t h e t i c a l l y s a t i s f a c t o r y y i e l d s of the (Z) ester _30 (entry 1). The bis(triraethylstannyl)cuprate reagent 43, under the same conditions that the (phenylthio)cuprate lh_ gave predominantly the (Z) isomer 30, afforded a mixture of isomers (entry 2); the reagents 44_ and 45_ gave ex c l u s i v e l y the (E) butenoate 29, while the (cyano)cuprate 46_ gave predominantly t h i s isomer (entries 3-6, r e s p e c t i v e l y ) . Our findings p a r a l l e l to some degree those obtained by other workers in i n v e s t i g a t i n g the reaction of alkylcopper reagents with 21 a,6-acetylenic esters. For example, Henrick and his co-workers found that the addition of lithium di-n-butylcuprate and n-butylcopper to methyl 2-butynoate (72) under i d e n t i c a l conditions lead to quite d i f f e r e n t results (equations 17, 18). In the former case, a mixture of - 21 -Table I I . Reaction of ethyl 2-butynoate with various (trimethylstannyl)copper reagents. Me,Sn Me,Sn CO.Et Me-C=C-COaEt 51 K Me C02Et 2 9 y Me 3 0 Entry Reagent, Conditions Y i e l d (%) b 29:30c 1 ii -48°C, 4 h 85 2:98 2 43 -48°C, 4 h 74 32:68 3 45_ -48°C, 4 h 82 >99:<1 4 44 -48°C, 3 h 68 >99:<1 5 44 -78°C, 3 h 76 >99:<1 6 46 -48°C, 2 h 86 96: 4 a A l l reactions were carried out i n THF with 1.3 equiv. of reagent. b Yield of isolated, d i s t i l l e d product(s). c As determined by glc (Column A). - 22 -the esters 73 a n d UL w e r e formed i n a r a t i o of 74:26, r e s p e c t i v e l y , while i n the l a t t e r case, a r a t i o of 98:2 resulted. Even higher s t e r e o s e l e c t i v i t y ( r a t i o of ]3_ to 74_, >99:<1) was observed when the addition with the n-butylcopper reagent was car r i e d out i n THF. Me-Csc-CO aMe 72 Q - BU Q - B " CO,Me E t « ° - - 7 8 ° C Me COiMe Me 73 74 0-Bu„CuU 74 26 ( 1 7 ) O-BuLi-Cul 98 2 ( 1 8 ) It has been w e l l - e s t a b l i s h e d 3 5 that the " k i n e t i c " product of the addition of organocopper reagents to a,B-acetylenic esters i s the unsaturated ester 76_ in which the newly introduced organic residue and the proton have been added i n a c i s manner (Scheme 8 ) . On the other hand, isomerization of the presumed intermediate ]5_ to 77_» followed by protonation of the l a t t e r species, gives r i s e to the isomer 78. By analogy, one may formulate the addition of (trimethylstannyl)copper reagents to a,8-acetylenic esters as proceeding through intermediates represented by 79_ and 80_ (Scheme 9 ) . It should be noted that although the intermediates 75, 77, 79, and 8p_ are conveniently represented as shown, t h e i r actual structures are not known. Al t e r n a t i v e - 23 -representations of the intermediates involved are the a l l e n i c structures 81 and 82. In f a c t , M a r i n o 3 6 has recently reported that an a l l e n i c intermediate may be involved in the addition of lithium dimethylcuprate to methyl propynoate. R"CuZLi R-CEC-CO.R 1  2 0 Scheme 8 It i s not at a l l obvious, however, why d i f f e r e n t copper reagents give d i f f e r e n t stereochemical r e s u l t s . One could speculate that the a n c i l l a r y ligand somehow a f f e c t s the s t a b i l i t y of the i n i t i a l i n t e r -mediate 7_9, so that the ease of Isomerization varies with the nature of the ligand. Perhaps there i s an e f f e c t on the strength of the C-Cu bond ( i f one exists) which must break for isomerization to occur, or on the oligomeric structures of the intermediates. - 24 -Z i Me,SnCu- Li R-C=C-C02R' 2 0 Z i Me,Sn Cu-Li R C02R' 79 Me,Sn R CO„R' 21 Me,Sn COjR' R Cu-Li 80 Me,Sn COjR1 22 Scheme 9 R OR' 81 z OCu-Li Me,Sn R OR1 82 z . OCu-Li The high s t e r e o s e l e c t i v i t y which we have observed in the forma-t i o n of the "thermodynamic" isomers 22_ using the (phenylthio)cuprate _14_ is unprecedented with respect to alkylcopper reagents. With alkylcopper reagents, only the " k i n e t i c " isomers _76 may be prepared i n high stereo-chemical purity; reactions under e q u i l i b r a t i n g or "thermodynamic" conditions lead to mixtures of stereoisomers. For example, reaction of - 25 -li t h i u m diraethylcuprate with methyl 2-decynoate (83) i n THF at -78°C affords almost e x c l u s i v e l y the ester 84_ (equation 19) while a s i m i l a r reaction i n THF-ether at 0°C affords a 39:61 mixture of the esters 84_ and 8>5_, resp e c t i v e l y (equation 20) a . The reason for th i s important diffe r e n c e might simply be that the trimethylstannyl group (A value = 3 7 0.94 kcal/mol ) i s less s t e r i c a l l y demanding than a methyl group (A value = 1.74 k c a l / m o l 3 8 ) . Thus for the intermediates represented by 79 and 80_, the s t e r i c i n t e r a c t i o n between the ester group and the t r i -methylstannyl group i n 80 should be much less than that between the ester group and the a l k y l group i n _79, whereas there i s not r e a l l y very much difference between j36_ and 87. Since the C-Cu bond i s probably quite long (- 1.9 A 3 9 ) , there should not be much of a s t e r i c i n t e r a c t i o n between the metal and the a l k y l group. n-C7H,5-CsC-C02Me 8 3 Me2CuLi THF,-78°C THF-Et2O,0°C 0-C 7 H, 5 C02Me n-C7H,5 r + K Me Me C02Me 84 99.8 39 85 0.2 61 (19) (20) n-C7H,5 C02Me Me Cu-Me i Li Me n-C7H,5 Cu-Li Me CO, Me 86 87 - 26 -An a l t e r n a t i v e exp l ana t i on i s that the i n i t i a l i n te rmed ia te formed i s the v i n y l coppe r spec ies 79_ wh ich, under e q u i l i b r a t i n g c o n d i t i o n s , i soraer izes to the a l l e n i c eno la te i n te rmed ia te 82. P ro tona t i on of 19_ a f f o rd s the (E) e s t e r 21. On the other hand, p ro tona t i on of 82_ leads to the therraodynamically more s t ab l e (Z) e s t e r 22. I f the s tereochemis t ry of the p ro tona t i on i s i n f l uenced by the r e l a t i v e s t a b i l i t i e s of the p roduct s , ( i . e . the t r a n s i t i o n s t a te f o r p ro tona t i on has p r o d u c t - l i k e cha rac te r ) t h i s would e x p l a i n why much b e t t e r s t e r e o s e l e c t i v i t y Is observed w i t h the ( t r i m e t h y l s t a n n y l ) c u p r a t e 14 than w i th a l k y l coppe r reagents . In other words, due to the s t e r i c i n t e r a c t i o n s mentioned above, the ( Z ) - 3 - t r i m e t h y l s t a n n y l e s t e r 22_ would be expected to be thermodynamical ly cons ide rab ly more s t ab l e than the (E_) e s t e r 2I_, wh i l e there would not be much d i f f e r e n c e between the s t a b i l i t y of 76_ and 78. I t i s t h i s d i f f e r e n c e i n r e l a t i v e s t a b i l i t i e s that accounts f o r the h igher s t e r e o s e l e c t i v i t y observed i n forming (Z)-B - t r i r ae thy l s tanny l -a-B -unsa tu ra ted e s t e r s (22) as compared w i t h 6 , 8 - d i a l k y l - a , 8 - u n s a t u r a t e d e s t e r s . Regardless of the r a t i o n a l e f o r format ion of the d i f f e r e n t i somers, from a s t r i c t l y s y n t h e t i c po in t of v iew, each of the i s omer i c e s te r s 29_ and 30_ may be r e a d i l y prepared by the appropr ia te choice of cuprate reagent(s ) and r e a c t i o n c o n d i t i o n s . The (Z) isomer 30 i s best prepared by employing the ( pheny l t h i o ) cuprate J^ 4_ s ince only t h i s reagent g i ves the "thermodynamic" product w i t h good s t e r e o s e l e c t i v i t y , wh i l e the (E) isomer 29_ i s best prepared us ing the copper reagent 44_ s ince t h i s reagent i s e a s i l y prepared from one equ i va len t each of ( t r i m e t h y l -- 27 -stannyl)lithium and the readily available CuBr«SMe2 complex and gives essentially exclusively the desired isomer. We found that many other <x, 8-acetylenic esters could be trans-formed highly stereoselectively into the corresponding (E_)-3-trimethyl-stannyl-2-alkenoates using the copper reagent kk_ or into the ( Z ) - 3 - t r i -methylstannyl-2-alkenoates using the (phenylthio)cuprate 14. Some of the results are shown in Table I I I . In almost every case, the (trimethylstannyDcopper reagent (44) effici e n t l y transferred the trimethylstannyl group to form essentially only one isomer, the (E) isomer 21. S i m i l a r l y , the (phenylthio)cuprate _14_ was usually very effective in converting the a-alkynoate _20_ into the corresponding (Z) unsaturated ester 22. Two of the esters examined, ethyl 4-^-butyldi-methylsiloxy-2-butynoate (55) and ethyl 4,4-dimethyl-2-butynoate (103), behaved anomalously. The a,8-acetylenic ester 5_5_ reacted with the (trimethylstannyD-copper reagent (44) to give predominantly the (E) butenoate 99_ in reasonable yield (entry 11) but reacted with the (phenylthio)cuprate _14_ to give only a low yield of the (Z) isomer 100 along with a small amount of a product arising from transfer of the phenylthio group, unsaturated ester 106 (equation 21, entry 12). I t is not clear why ester 55_ behaves in this manner since the next higher homolog (ester j38_, entry 13) behaves quite normally. However, i t is likely that the reasons are related to the electron-withdrawing effects of the oxygen functionality close to the triple bond. - 28 -Table I I I . Convers ion of a ,8 - a c e t y l e n i c e s te r s i n t o ( Z ) - and ( E ) - 3 - t r i r a e t h y l s t a n n y l - 2 - a l k e n o a t e s . R - C 5 C - C 0 , R ' 2 0 Me ,Sn Me ,Sn C0 2 R' R C O , R ' R 21 22 21:22 b Entry 20 R R' Conditions a (pro ducts) Yield (%) c 1 53 Et Et A >99:<1 ( 89:90 ) 80 2 d 53 Et Et B 2:98 ( 89:90 ) 76 3 1\_ i " P r Me A >99:<1 ( 91:92 ) 77 4 7i_ i " P r Me B 6:94 ( 91_:92 ) 73 5 68 cyclopropyl Me A >99:<1 ( 93:94 ) 81 6 68 cyclopropyl Me B 5:95 ( 93:94 ) 72 7 57_ 2-(2-cyclopentenyl)ethyl Me A >99:<1 ( 95:96_ ) 84 8 57 2-(2-cyclopentenyl)ethyl Me B 2:98 ( 95:96 ) 77 9 59 (3-cyclohexenyl)methyl Me A >99:<1 ( 97_:98 ) 72 10 59 (3-cyclohexenyl)methyl Me B 3:97 ( 97:98 ) 71 11 55 t^BuMe2S10CH2 Et A 95: 5 ( 99:100) 75 12 55 _t-BuMe2SiOCH2 Et B 9:91 ( 99:100) 29 e 13d 88 t-BuMe2SiOCH2CH2 Me B 4:96 (101:102) 81 14d 103 _t-Bu Et c f 8:92 (104:105) 84 15d 103 t-Bu Et D 2:98 (104:105) 86 16 103 t-Bu Et E« 12:80 (104:105)" 79 - 29 -Table III (cont'd) A: reagent 44 (1.3 equiv.), THF, -78°C, 3 h. B: reagent 14 (1.3 equiv.), THF, -48°C, 4 h. C: reagent 14 (3.0 equiv.), THF, -78°C, 6 h. D: reagent 14 (3.0 equiv.), THF, -48°C, 4 h. E: reagent 44 (3.0 equiv.), THF, -20°C, 6 h. k As determined by glc analysis on column A. 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. ^ Taken from reference 26. e Also i s o l a t e d (35% y i e l d ) was the corresponding product of phenylthio transfer (see t e x t ) . f In the presence of 1.7 equiv. of ethanol. g HMPA (10% by volume) was added p r i o r to addition of the acetylenic ester. h A t h i r d component, thought to be ethyl (E)-4,4-dimethyl-2-trimethylstannyl-2-pentenoate (107), was also present. - 30 -Me3Sn + , [Me,SnCuSPh]Li Me,Sn C02Et -)-SiOCHrC5C-C02Et — « • I F=S 1 0 0 ( 2 1 ) ^ 1 14 ->-SK>-' 55 + PhS COaEt 106 The spectral data of the products shown i n Table III are In complete agreement with the assigned structures. In general, the *H nrar spectra of these compounds were very useful i n ascertaining t h e i r stereochemistry. For example, the *H nmr spectrum of ester 99_ showed the signals expected f o r a _t-butyldiraethylsilyl group (a 6-proton sin g l e t at 6 0.15 and a 9-proton singlet at 6 0.98), a trimethylstannyl group (a 9-proton si n g l e t at 6 0.26 with s a t e l l i t e peaks due to Sn-H coupling, J_ = 53/56 Hz) and an eth y l ester moiety (a 3-proton t r i p l e t at 6 1.35 and a 2-proton quartet at 6 4.19, J_ = 7 Hz). In addition, the y-protons gave r i s e to a doublet (J_ = 3 Hz) at 6 4.94 (with s a t e l l i t e peaks due to Sn-H coupling, J = 30 Hz) while the signal due to the o l e f i n i c proton appeared as a t r i p l e t (J_ = 3 Hz) at 6 5.94 (with s a t e l l i t e peaks due to Sn-H coupling, J_ = 72 Hz). The *H nmr spectrum of the geometrically isomeric ester 100 was very s i m i l a r to that of 99, but d i f f e r e d s i g n i f i c a n t l y i n two important respects. In p a r t i c u l a r , - 31 -the p o s i t i o n of the signal due to the Y - P r o t o n s of 99_ (6 4.94) was considerably downfield from the signal (6 4.49) due to the corresponding protons of the isomeric ester 100. Thus i t i s reasonable to suggest that the y p r o t o n s are c i s to the ester group i n 99_ but trans to the ester group i n 100. Also, the magnitude of the coupling constant associated with coupling of 1 1 7 S n and 1 1 9 S n to the o l e f i n i c proton was quite d i f f e r e n t for the two isomers. I t i s known 1 0 c that with organotin compounds i n which the t i n atom and a hydrogen atom are v i c i n a l on an o l e f i n i c linkage, Js n-H i s larger when they are trans to each other than when they are c i s to each other. In esters 99_ and 100, Js n-H associated with the o l e f i n i c protons are 72 Hz and 114 Hz, respectively. This also indicates that the assigned structures 99 and 100 are correct. Analogous comparisons were also made In assigning the structures of the other products shown i n Table I I I . Reactions of the a, 8-acetylenic ester 103 with ( t r i m e t h y l -stannyl)cuprate reagents, and the s t r u c t u r a l e l u c i d a t i o n of the products, were not as straightforward as with the other a,B-acetylenic 2 6 esters. Previous r e s u l t s from our laboratories had shown that the ester 103 reacts with an excess of the (phenylthio)cuprate 14_ under " k i n e t i c " conditions (which normally produce predominantly the (E_) isomer 21) to afford mostly the (Z) isomer 105; reaction under "thermo-dynamic" conditions gave very s i m i l a r r e s u l t s (Table I I I , entries 14,15). These results may be r a t i o n a l i z e d on the basis of d e s t a b i l i z a -t i o n of the k i n e t i c intermediate _79 (R = _t-Bu) by the i n t e r a c t i o n of the bulky _t-butyl group with the ester group. That the trimethylstannyl - 32 -group was i n f a c t i n the 8 - p o s i t i o n (and not i n the a - p o s i t i o n ) i n e s t e r 105 was shown by reduc t i on of t h i s e s t e r to the a l c o h o l 108 (equat ion 22) . The magnitude of the coup l i n g constant (*H nmr spect roscopy, J. = 6 Hz) between the methylene protons and the o l e f i n i c proton of a l c o h o l 108 i n d i c a t e d that the o l e f i n i c proton was i n the 2 - p o s i t i o n . Hence, the t r i m e t h y l s t a n n y l group i n e s t e r 105 must have been i n the 3 - p o s i t i o n . (22) 105 108 The ( t r i m e t h y l s t a n n y l ) c o p p e r reagent (44) normal ly g i ve s e x c l u s i v e l y the (E) isomer 21_ even under cond i t i on s (THF, -48°C) i n which the ( pheny l th i o ) cup ra te ^4_ a f f o r d s mainly the (Z) isomer 22. We found that the copper reagent 44_ reacted qu i t e s l u g g i s h l y w i t h the e s t e r 103 at -78°C. At h igher temperatures ( -20°C), the r e a c t i o n proceeded to complet ion but, as i n r e a c t i o n s w i t h the ( pheny l t h i o ) cup ra te _14, a l s o a f fo rded mainly the (Z) isomer 105 (equat ion 23; Table I I I , en t ry 16). Thus i t appears that the s t e r i c bulk of the _ t -buty l group prec ludes e f f i c i e n t format ion of the (E) isomer 104. In c o n t r a s t , e s te r s w i t h the s t e r i c a l l y l e s s demanding I sopropy l ( e s te r 71) and c y c l o p r o p y l ( e s te r 68) groups reacted smoothly w i t h the copper reagent 44_ at -78°C to p rov ide e s s e n t i a l l y e x c l u s i v e l y the (E) e s t e r s 9l_ and j)3_, r e s p e c t i v e l y (Table I I I , e n t r i e s 3, 5 ) . - 33 -Me,Sn 104 CO.Et t-Bu-CSC-COaEt 103 Me,SnCu-SMe3 4 4 Me,Sn C02Et V / 105 (23) Hv /SnMe, C0,Et 107 As i n the case of the e s t e r 105, there was some i n i t i a l doubt as to the p o s i t i o n of the t r i m e t h y l s t a n n y l group i n e s te r 104. The o l e f i n i c proton of t h i s compound gave r i s e to a s i n g l e t at 6 5.84 (w i t h s a t e l l i t e peaks due to Sn-H coup l i n g , J_ = 85 Hz) i n the *H nmr spectrum. The magnitude of ^Sri-H i n d i c a t e d that the t r i m e t h y l s t a n n y l group and the o l e f i n i c proton were c i s but d id not i n d i c a t e whether the t r i m e t h y l s t a n n y l group was s i t u a t e d a lpha or be t a . Reduct ion of e s t e r 104 w i t h d i i sobuty la luminum hydr ide a f fo rded the a l c o h o l 109 (equat ion 24). The 1 H nmr spectrum of a l c o h o l 109 i n d i c a t e d that the hydroxymethyl group and the o l e f i n i c proton were geminal ( 3jJ = 6 Hz) and t h e r e f o r e , by i n f e r e n c e , that the t r i m e t h y l s t a n n y l group i n the p recu r so r e s t e r 104 was beta as shown. - 34 -There was also i s o l a t e d from the reaction of the ( t r i m e t h y l -stannyl) copper reagent (44) with the ester 103 a small amount of another isomer t e n t a t i v e l y i d e n t i f i e d as the a-trimethylstannyl ester 107 (equation 23). The o l e f i n i c proton of this ester gave r i s e to a s i n g l e t at 6 5.58 (with s a t e l l i t e peaks due to Sn-H coupling, J_ = 78 Hz) i n the *H nmr spectrum. The magnitude of £sn-H i n d i c a t e d t n a t t h e trimethyl-stannyl group and the o l e f i n i c proton were c i s . Since t h i s ester was obviously not the 8-triraethylstannyl ester 104, i t was assigned structure 107 by the process of elimination. In summary, i t seems that the reactions of the (phenylthio)-cuprate _14_ and the copper reagent 44_ with a, 8-acetylenic esters are, with a few exceptions, quite general. Many 8-trimethylstannyl-oc, 8-unsaturated esters of general structure 21_ may be prepared with very high s t e r e o s e l e c t i v i t y using the copper reagent 44_ while the isomeric esters 22 may be prepared, also with high s t e r e o s e l e c t i v i t y , using the cuprate reagent 14. Although the (cyano)cuprate 46_ reacted with ethyl 2-butynoate (51) (THF,-48°C, 2h) to afford predominantly the (E) isomer 29_ (equation 25; Table I I , entry 6), the reaction could not be generalized to - 35 -homologous e s te r s as could the r eac t i on s of the (pheny l th i o ) cup ra te J_4_ and the ( t r i r ae thy l s t anny l ) coppe r reagent (44) . Thus, r e a c t i o n of e t h y l 2-pentynoate (53) w i t h the (cyano)cuprate under very s i m i l a r c o n d i -t i on s (THF, -48°C, 2.5 h) a f f o rded a 88:12 mixture of the i somer i c e s t e r s J39_ and 90_, r e s p e c t i v e l y , along w i th some (16%) s t a r t i n g m a t e r i a l 53. The r e a c t i o n proceeded to complet ion i f a l lowed to proceed f o r a longer pe r iod of time (-48°C, 6 h) ; i n t h i s case, a 77:23 mixture (86% y i e l d ) of the e s te r s 89_ and 90_, r e s p e c t i v e l y , r e s u l t ed (equat ion 26). From these p r e l i m i n a r y r e s u l t s , i t appears that the (cyano)cuprate 46 i s qu i t e s e n s i t i v e to the nature of the a c e t y l e n i c e s t e r and f u r t h e r work may show i t to be a u s e f u l reagent f o r the s e l e c t i v e t r a n s f e r of a t r i m e t h y l s t a n n y l group to m u l t i f u n c t i o n a l s ub s t r a te s . Me-CSC-CO.Et Et-CsC-COaEt 5 3 |Me,SnCuCN]Li Me,Sn Me,Sn CO.Et K + y 46 -48°C. 2h Me C02Et Me 29 30 9 6 4 [MeaSnCuCN]Li Me,Sn Me,Sn CO.Et K + y . / \ J (26) 46 -48°C. 6 h Et C02Et Et 8 9 9 0 7723 D. Synthesis and transmetalatlon of alkyl (E)-2,3-bis(trlaethyl 8 tanny1)-2-alkenoates Having e s t a b l i s h e d the r e a c t i v i t y p a t t e r n of a number of ( t r i r a e t h y l s t anny l ) c up r a t e reagents towards a ,8 - a c e t y l e n i c e s t e r s , we turned our a t t e n t i o n to the p o s s i b i l i t y of t r app ing the i n te rmed ia te s 79 and 80 w i t h e l e c t r o p h i l e s (Scheme 10). As mentioned i n the i n t r o d u c -Scheme 10 - 37 -t i o n , i f the intermediate species could be trapped with e l e c t r o p h i l e s (Y +) other than proton, unsaturated esters of general structures 35_ and 36 could be prepared. In turn, these materials could conceivably be converted into many other d e r i v a t i v e s , such as the protected alcohols 110 and 111 or the dienes 112 and 113. C l e a r l y , successful execution of these p o s s i b i l i t i e s could constitute a useful entry into highly-substituted v i n y l l i t h i u m reagents, i f the products such as 110-113 would be amenable to transmetalation. Unfortunately, no trapped products were obtained when ethyl 2-butynoate was allowed to react with any of the cuprate reagents 14, 44, or _45_ and the reaction mixture was subsequently treated with e l e c t r o p h i l e s such as iodomethane, benzyl bromide or cyclohexanone (equation 27). In general, when the reactions were carried out at low temperatures (less than -48°C), subsequent workup afforded only the protonated ester(s) 29_ (and _30_, when the (phenylthio)cuprate _14_ was employed), while reactions at higher temperatures (-20°C - room temperature) gave r i s e to mixtures of the protonated ester(s) _29_ (and 30) and a higher-boiling by-product. The addition of HMPA and/or triethylphosphite 1* 0 to the reaction mixture did not res u l t i n the formation of trapped products. A small sample of the higher-boiling by-product was obtained as a col o r l e s s o i l by preparative glc and i d e n t i f i e d as ethyl (E_)-2,3-bi.s-(trimethylstannyl)-2-butenoate (114). The r e l a t i v e l y simple *H nmr spectrum of th i s material was read i l y interpreted; i t consisted of two sharp 9-proton s i n g l e t s at 6 0.15 and 0.26 (with s a t e l l i t e peaks due to - 38 -Sn-H c oup l i n g , J_ = 52/54 Hz and 53/55 Hz, r e s p e c t i v e l y ) , a 3-proton t r i p l e t at 6 1.28 (J_ = 7 Hz ) , a 3-proton s i n g l e t at 6 2.22 (w i t h s a t e l l i t e peaks due to Sn-H coup l i n g , J_ = 11 Hz and 47/49 Hz) and a 2-proton quartet at 6 4.17 (J_ = 7 Hz ) . Thus t h i s m a t e r i a l conta ined two t r i m e t h y l s t a n n y l groups, an e t h y l e s t e r f u n c t i o n and a v i n y l methyl group. Taking i n t o c o n s i d e r a t i o n the s t r u c t u r e of the s t a r t i n g m a t e r i a l , t h i s compound was ass igned the s t r u c t u r e 114. Th is s t r u c t u r a l assignment was supported by the i r spectrum which showed a band at 1680 c m - 1 a t t r i b u t a b l e to the carbony l s t r e t c h i n g frequency of an a , 8-unsaturated e s te r and a band at 775 cm " 1 a t t r i b u t a b l e to the Sn-Me rock ing frequency of a t r i m e t h y l s t a n n y l group. - 39 -Me,Sn C02Et Me SnMe, 114 Compound 114 represents a novel, new type of organotin k 1 d e r i v a t i v e . Although 1,2-bis(trialkylstannyl)ethylenes are known , a l k y l (E_)-2,3-bis(trimethylstannyl)alkenoates have not been reported previously. Therefore, we decided to (a) try to improve the y i e l d of ester 114, (b) determine whether or not th i s reaction i s generally applicable to other <x, 8-acetylenic esters and (c) f i n d a means of using compounds l i k e ester 114 as precursors to functionalized v i n y l l i t h i u m reagents. After some experimentation, i t was found that when ethyl 2-butynoate (51) was allowed to react (THF, -48°C, 30 min; 0°C, 3 h) with 2.5 equiv. of the reagents 44_ or 4_5, the bis(trimethylstannyl) ester 114 was produced i n 70-75% y i e l d . S i m i l a r l y , other a,8-acetylenic esters (20) could be converted smoothly into the corresponding (E_)-a,8-bis(trimethylstannyl)-a,8-unsaturated esters (115) i n reasonable y i e l d s . These results are summarized i n Table IV. Although these r e s u l t s require l i t t l e a d d i t i o n a l comment, i t should be emphasized that, in each case (except entry 10, see below), the indicated product was, i n addition to hexamethylditin, the only substance obtained upon d i s t i l l a t i o n of the crude material. Furthermore, the y i e l d s were consi s t e n t l y good, and the reaction was successful not only with - 40 -Table IV. Preparation of (E)-a,8-bis(trimethylstannyl)-a , B-unsaturated esters. R-CHC-COjR1 2 0 4 4 or 4 5 -48°C—0°C Me,Sn CO.R' R SnMe, 115 Entry a,8-Acetylenic Ester Yield of 115 (*) a 20 R R' 115 Reagent 44_ Reagent 4_5 1 Sl_ Me Et 114 73 (84) b 74 2 53 Et Et 116 79 76 3 71_ i-Pr Me 117 70 74 4 61_ H - C6 H13 Me 118 79 86 5 68 cyclopropyl Me 119 77 73 6 57 2-(2-cyclopentenyl)ethyl Me 120 76 71 7 59 (3-cyclohexenyl)methyl Me 121 82 82 8 55 t-BuMe2S10CH2 Et 122 74 70 9 88 t-BuMe2S10CH2CH2 Me 123 72 69 10 124 H Me 125 41 c 45c a Y i e l d of d i s t i l l e d , p u r i f i e d product. Reaction performed on 0.3 mmol of 20. b Reaction performed on 10 mmol of ethyl 2-butynoate. c Also i s o l a t e d was 12% of a material i d e n t i f i e d as methyl 3,3-bis(trimethylstannyl)propanoate (126). - 41 -Table V. H nmr chemical s h i f t s of y-protons of esters 21, 22 and 115. Entry R R' (Ester 21) 6 a (Ester 22) 6 a (Ester 115) 6 a 1 Me Et (29) 2.42 (30) 2.12 (114) 2.22 2 Et Et (89) 2.85 (90) 2.41 (116) 2.47 3 i-Pr Me (91) 4.02 (92) 2.72 (117) 2.64 4 n-C 6H 1 3 Me (127) b 2.86 (128) b 2.41 (118) 2.47 5 cyclopropyl Me (93) 3.27 (94) 1.75 (U9) 1.77 6 2-(2-cyclopentenyl)ethyl Me (95) 2.95 (96) 2.45 (120) 2.52 7 (3-cyclohexenyl)methyl Me (97) 2.89 (98) 2.38 (121) 2.53 8 t-BuMe2S10CH2 Et (99) 4.94 (100) 4.49 (122) 4.38 9 t-BuMe 2SiOCH2CH2 Me (101) c 3.10 (102) c 2.63 (123) 2.72 a Chemical s h i f t s were recorded i n CDC1 3. D Prepared by R. Urech i n our lab o r a t o r i e s . c Prepared by H. Morton i n our lab o r a t o r i e s . - 42 -"simple" a,8-acetylenic esters but also with f u n c t i o n a l i z e d substrates. A l l of the products shown exhibited spectra ( i r , *H nrar, ms) i n complete agreement with the assigned structures. The stereochemical assignments with respect to esters 115 were made on the basis of *H nmr spectroscopy. S p e c i f i c a l l y , the chemical s h i f t of the Y ~ P r o t o n s of the esters 115 were compared with those of the corresponding protonated esters 21_ and 22. The appropriate data are shown in Table V. In each case, the Y~P r°tons of the compounds 21, i n which the ester group and the a l k y l group are c i s , resonate downfield from the Y~protons of the corresponding geometric isomers 2_2_, in which the ester group and the a l k y l group are trans. Since the Y~P r°tons of the products 115 resonate at frequencies much closer to those of the Y~protons of the corresponding ester 22_ than to those of the isomer 21, i t i s highly l i k e l y that the stereochemical r e l a t i o n s h i p between the ester group and the a l k y l group i n compounds 115 and 22_ i s the same. It should be noted that the Y~protons of esters 140-143 resonate at 6 1.88 1 1 2, 1.90 1 0 c, 2.14 4 2, and 2.05 1 0 c, res p e c t i v e l y . Therefore, a c i s or trans trimethylstannyl group has only a small e f f e c t on the chemical s h i f t of Y -P r°tons i n ct-trimethylstannyl-a,^-unsaturated esters. 140 R=Me.R' = H 142 141 R=Et , R'=SnMe, 143 - 43 -The only a,8-acetylenic ester investigated which did not react cleanly to form the corresponding bis(trimethylstannyl) ester was methyl propynoate (124) (Table IV, entry 10). In t h i s case, i n addition to the expected ester 125 there was formed a substantial amount of the saturated ester 126 (g l c r a t i o of 125:126 = 75:25) (Scheme 11). The ester 126 i s probably formed by protonation of the intermediate 133 by the r e l a t i v e l y a c i d i c alkynyl proton of the s t a r t i n g ester 124, followed by further reaction of the resultant ester 134 with another equivalent of a (trimethylstannyl)copper reagent. Z i Me,SnCu-Li + H-C5C-C02Me 124 z i Me,Sn Cu- Li H C02Me 133 z i Me,SnCu-Li Me,Sn C02Me H SnMe3 125 H-C=C-CO,Me Me,Sn H M COsMe 134 z i Me,SnCu-Li Me,Sn Me,Sn CO„Me 126 Scheme 11 - 44 -Although the bis(trimethylstannyl) ester 125 had no y~P rotons as beacons to aid i n the assignment of stereochemistry, the coupling constants between the o l e f i n i c proton and the t i n atoms were diagnos-t i c . Thus t h i s proton gave r i s e to a s i n g l e t at 6 7.47 with s a t e l l i t e peaks due to Sn-H coupling, J_ = 88/92 Hz. This i s i n l i n e with a geminal or c i s but not a trans (JjSn-H - 1 2 0 Hz) r e l a t i o n s h i p between the t i n atoms and the o l e f i n i c proton 1° c. Since the geometric isomer of ester 125 would have a trans related trimethylstannyl group and o l e f i n i c proton, the ester 125 must possess the stereochemistry shown. P a r t i c u l a r l y s t r i k i n g i n Table V are entries 3 and 5. The difference i n chemical s h i f t between the y-protons of the corresponding isomers 21_ and Tl_ i s usually about 0.4 ppm. When the y~proton i s t e r t i a r y (entries 3 and 5), however, this difference i s about 1.4 ppm. This i s probably due to the close proximity of the t e r t i a r y hydrogen to the deshielding cone of the ester i n the preferred conformation(s) of the compounds 9l_ and 93. It i s quite l i k e l y that products 115 are formed as a result of i n i t i a l addition of the cuprate reagent 44_ and 45 to the a,B-acetylenic-ester 20_, followed by isomerization and r a d i c a l coupling of the intermediate 79_ with another equivalent of cuprate reagent 44_ or 45_ upon warming the reaction mixture to 0°C. The thermal coupling of organo-copper species has previously been employed as a means of forming 43 dimers . An analogous reaction occurs when 86_ i s oxidized with dry oxygen at -78°C i n the presence of a large excess of lithium dimethyl-3 5 cuprate: ester 135 i s formed i n " f a i r y i e l d " (equation 28) a . - 45 -D-C7H« CO,Me MexCuLi.O, n-C 7H 1 5 C0 2Me Me -Me -78°C Me Li 86 135 Regardless of the mechanism by which the bis(trimethylstannyl) esters 115 are formed, we could now r e a d i l y prepare these compounds and we wanted to see whether or not these materials would be useful i n r e a l i z i n g our o r i g i n a l goal of preparing reagents corresponding to the general synthons 39_ and/or 40_. One p o s s i b i l i t y Involved t r e a t i n g the esters 115 d i r e c t l y with an a l k y l l i t h i u m i n the hope that the a-trimethylstannyl group would be transmetalated s e l e c t i v e l y without interference from the ester moiety or from the 8-trimethylstannyl group. If the r e s u l t i n g enolate anion could be trapped with e l e c t r o p h i l e s other than proton, the preparation of esters (equation 29) would have been achieved. We were very pleased to f i n d that treatment of the b i s ( t r i m e t h y l -stannyl) ester U4_ with 1.1 equivalents of MeLi (THF, -98°C, 20 min) followed by addition of iodomethane to the resultant yellow solution (-98°C, 30 min; -78°C, 1 h) afforded, a f t e r appropriate workup, a single v o l a t i l e product i n 84% y i e l d . The *H nmr spectrum of this material indicated that i t contained only one trimethylstannyl group (9-proton s i n g l e t at 6 0.08 with s a t e l l i t e peaks due to Sn-H coupling, J_ = 53/55 Hz), an ethyl ester moiety (3-proton t r i p l e t at 6 1.27 and 2-proton - 46 -* . S n C < y * 1) RLi Me,Sn CO , * 115 3 6 quartet at 6 4.18, J_ = 7 Hz ) , and two v i n y l methyl groups (two 3-proton qua r te t s at 6 1.93 and 2.01, J_ = 1 Hz) . There were, t h e r e f o r e , only three po s s i b l e s t r u c t u r e s (136-138) f o r t h i s new compound. The magnitude of the Sn-H coup l i ng constant (J_ = 49 Hz) to one of the v i n y l methyl groups (6 2.01) i n d i c a t e d that i t was geminal to the t r i m e t h y l -s t anny l group. Thus, s t r u c t u r e 136 was r u l ed out. S t r u c tu re 137 could be e l i m i n a t e d i f I t could be shown that the t r a n s m e t a l a t i o n - t r a p p i n g proceeded w i t h r e t e n t i o n of c o n f i g u r a t i o n . A l though i t i s we l l - known 5 w i t h other v iny l s tannanes that t h i s process proceeds w i t h r e t e n t i o n of c o n f i g u r a t i o n , t h i s has not been shown f o r compounds i n which the t i n atom i s a lpha to an e s te r group. That the o v e r a l l process occurred w i t h r e t e n t i o n of c o n f i g u r a t i o n (and the re fo re that the e s t e r i s o l a t e d possessed s t r u c t u r e 138) was - 47 -shown as follows. Reduction of the ester 138 with diisobutylaluminura hydride afforded the alcohol 139 which upon transraetalation-protonation (2 equivalents of MeLi, THF, 0°C; NHi+Cl-HjO) gave (E)-2-methyl-2-buten-l-ol (140) (equation 30), which was i d e n t i c a l ( g l c , t i c , *H nmr) with an authentic sample of the same compound obtained by reduction of t i g l i c aldehyde. Me SnMe, Me,Sn Me Me,Sn C02Et W W W M e CO a Et Me' C02Et Me Me 136 137 138 Me,Sn C02Et 138 DIBAL Me,Sn 139 1) 2 MeLi 2) NH 4 CI-H 20 H Me Me OH 140 (30) We have also allowed the intermediate l i t h i o species from 114 to react with other e l e c t r o p h i l e s to produce esters of general structure 141 (Table VI). It may be seen from Table VI that the resultant anion coupled with reactive a l k y l a t i n g reagents ( e n t r i e s 1-3) and cyclohexanone (entry 4) at low temperature (-78°C) to af f o r d the - 48 -Table V I . T ransmeta la t ion of e t h 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-butenoate and r e a c t i o n of the i n te rmed ia te anion w i t h e l e c t r o p h i l e s . Me.Sn C0 2 Et 1 ) M e L i Me.Sn C0 2 Et \_/ w M e ' N i n M e , 2) Y + Me Y 114 141 Ent ry Y+ Product Y Y i e l d (%) a 1 Mel 138 CH 3 84 2 a l l y l bromide 142 CH.2~^H=CH2 79 3 benzy l bromide 143 CH 2Ph 76 4 cyclohexanone 144 1 -hydroxycyc lohexy l 71 5 n - b u t y l i od i de 145 n—C^Hg 5 0b 6 H+ 30 H 80 -90C a Y i e l d of i s o l a t e d , p u r i f i e d product . D React ion was a l lowed to warm to room temperature. A s i g n i f i c a n t (40%) amount of protonated e s t e r 3(3 was a l s o p resent . c A l so conta ined = 7 - 10% of e s te r 29. - 49 -expected adducts 141 i n reasonable y i e l d s . It should be noted that, i n each case, the indicated product was e s s e n t i a l l y the only v o l a t i l e ( g l c analysis) material produced and could be p u r i f i e d by simple d i s t i l l a t i o n (entries 1,2) or by d i s t i l l a t i o n a fter removal of excess e l e c t r o p h i l e by chromatography (entries 3,4). When cyclohexanone was the e l e c t r o p h i l e (entry 4), chromatography also served to remove a small amount (5%) of the protonated ester 30. With a less reactive e l e c t r o p h i l e , 1-iodo-butane, no trapped product was obtained when the reaction was c a r r i e d out at -78°C; when the reaction mixture was allowed to warm to room temperature (entry 5), some trapped product was produced but was accompanied by a substantial amount of the protonated ester 30. More work i s required i f t h i s reaction i s to be extended so that the intermediate anion may be e f f i c i e n t l y trapped by e l e c t r o p h i l e s less reactive than those shown in Table VI, entries 1-4. The stereochemical assignments of the esters 141 were made primarily on the assumption that the transraetalation-trapping process occurs with o v e r a l l retention of configuration as shown above for ester 138. In addition, the positions of the signals due to the v i n y l methyl protons i n the *H nmr spectra were consistent with a trans r e l a t i o n s h i p between the v i n y l methyl group and the ester moiety - they were u p f i e l d from what would be expected i f these groups were c i s . For example, the y-protons of esters 29^  and 30^  resonate at 6 2.42 and 2.12, respec-t i v e l y . In comparison, the y~P rotons of esters 138, 142, 143, 144 and 145 (Table VI) resonate at 5 2.01, 2.03, 2.12, 2.20 and 2.02, res p e c t i v e l y . - 50 -Although only one isomer was detected i n each case when the intermediate anion was trapped with e l e c t r o p h i l e s other than proton, protonation of the intermediate i n v a r i a b l y gave r i s e to small amounts (7 to 10% by glc analysis) of the thermodynamically less stable ester 2_9 along with the expected ester 30_ (equation 31; Table VI, entry 6). Neither the nature of the proton source (aqueous ammonium chloride, methanol, or a c e t i c acid i n ether) nor inverse addition (of a THF solution of the anion to solutions of methanol or acetic acid i n ether at -98°C) s i g n i f i c a n t l y affected the amount of the isomer 23_ produced. The reasons for this anomaly remain obscure. Me.Sn COaEt D MeLi Me.Sn Me,Sn CO,Et H — " H + W (31) Me SnMe, Me CO,Et M « 1 1 4 2 9 3 0 - 1 0 : 9 0 Thus, although d i r e c t trapping of intermediates _79_ and/or 80_ with el e c t r o p h i l e s was not successful, a two-step conversion of a,8-acety-l e n i c esters into compounds of general structure 36 has been r e a l i z e d . These products should be r e a d i l y transformed into highly substituted v i n y l l i t h i u m reagents corresponding to the generalized d synthon 40. R Y 4 0 - 51 -As a method p o t e n t i a l l y complementary to that described above, i t was decided that perhaps the intermediate 7_9_ could be trapped with iodine (equation 32). Treatment of the (expected) iodide 146 with _t-butyllithium should afford an intermediate l i t h i o species which should react with e l e c t r o p h i l e s to give esters 35_. C l e a r l y , i f successful, t h i s would be another two-step a l t e r n a t i v e to one of our o r i g i n a l goals. Previous work with a l k y l cuprate reagents had shown that the intermediate copper species 86_ could be trapped with iodine to give iodide 147 i n "high y i e l d " a (equation 33). We were mildly surprised, therefore, to fin d that treatment of the intermediate formed by addition of the (trimethylstannyl)copper reagent (44) to ethyl D-C7H„ C02Me M e ^ ^ C u - U i Me 86 i . D-C,H, -78°C MeH 147 COaMe (33) 2-butynoate (THF, -78°C) with iodine (THF, -78°C) afforded, a f t e r appropriate workup, none of the desired iodinated product, but rather a - 52 -mixture of ethyl (E_)-3-trimethylstannyl-2-butenoate (29) and s t a r t i n g alkynoate 5J_ in rat i o s (glc analysis) varying from = 80:20 to = 20:80 (equation 34). 1) Me,SnCu-SMea Me.Sn Me-CSC-CO,Et \=a, + 51 (34) 2) I, / \ Me CO.Et 3) NH4CI 2 9 This same phenomenon was observed by Cox and Wudl n n when they attempted to trap the same intermediate copper species with bromine or mercuric c h l o r i d e . Since quenching of an aliquot of the reaction mixture (removed before the addition of B r 2 or HgCl 2) with methanol showed that no butynoate remained, while quenching with either e l e c t r o -p h i l e returned 60% butynoate and only 20% _29_, they postulated the following (Scheme 12). They reasoned that (a) the i n i t i a l addition i s fast and reversible (equation A), (b) protonation of the vinylcopper intermediate 148 i s fast and i r r e v e r s i b l e (equation B), (c) the ( t r i a l k y l s t a n n y l ) c u p r a t e reagent i s not rea d i l y protonated (equation C), (d) protonation of the cuprate intermediate 148 drives the equilibrium to the right and (e) strong e l e c t r o p h i l e s drive the equilibrium to the l e f t by reacting with the ( t r i a l k y l s t a n n y l ) c u p r a t e reagent faster than with the intermediate 148. These postulates are harmonious with our findings and may have important consequences In subsequent work with these ( t r i a l k y l s t a n n y l ) c u p r a t e reagents. - 53 -Me-CsC-CO aEt 51 z i Me,SnCu-Li Z Me,Sn Cu-Li X Me C02Et 148 z i Me,Sn Cu-Li Me C02Et 148 H + B Me,Sn H K Me COaEt 2 9 Me3SnCu-Li MeOH C no reaction Z = PhS,' PhjPOO ", MeaS Br Scheme 12 E. Reaction of (trimethylstannyl)copper reagents with ai-halo—g,B- acetylenic esters* Intramolecular alleviations. We have also b r i e f l y examined the p o s s i b i l i t y of trapping intramolecularly the intermediate derived from the addition of (trimethylstannyl)copper reagents to a,8-acetylenic esters. Although intermolecular trapping of the intermediate with e l e c t r o p h i l e s other than proton was not possible, i t was f e l t that the intramolecular process should be much more f a c i l e (Scheme 13). If successful, t h i s would provide an i n t e r e s t i n g synthetic route to c y c l i c 8-trimethyl-- 54 -stannyl-a,8-unsaturated esters of general structure 151. Li Z \ i Cu COaR C02R X-(CHa)n-CHC-CO,R X-(CHa), SnMe, SnMe, 149 151 150 Scheme 13 The r e q u i s i t e co-substituted-a,8-acetylenic esters 149 were 6-bromo-2-hexynoate (154) was prepared from 5-tetrahydropyranyloxy-l-pentyne (152) v i a deprotonation-acylation to afford ester 153 followed by treatment of the l a t t e r substance with triphenylphosphine dibromide 45 in dichloromethane . Reaction of the bromide 154 with sodium iodide i n acetone provided the iodide 155, while hydrolysis (PPTS, methanol) of the THP ether 153 followed by mesylation (methanesulfonyl ch l o r i d e , pyridine) of the resultant alcohol 156 afforded the mesylate 157. The homologous bromo 160 and iodo esters 161 were prepared using e s s e n t i a l l y i d e n t i c a l procedures. Reaction of the bromo ester 154 with the (trimethylstannyl)copper reagent (44) (THF, -78°C) proceeded without incident to give the expected (E) ester 162 i n 82% y i e l d (equation 35). S i m i l a r l y , reaction with l i t h i u m (phenylthio)(trimethylstannyl)cuprate (14) (THF, -48°C) r e a d i l y prepared v i a standard methods (Scheme 14). Thus, methyl - 55 -THP0-(CH 2)-C2C-H 152* 158' 1) MeLi 2) CIC02Me THP0-(CH 2)-CSC-C0 2Me 153 159 s 1) PPTS/MeOH 2) MsCI/pyr MsO-(CH2)n-CSC-C02Me 157 1 Ph 3P-Br 2 Br-(CH2)-C=C-C02Me Nal/acetone l-(CH 2)-C5C-C0 2Me 154 160 a n = 3 ' n = 4 155 161 3 Scheme 14 proceeded smoothly to give a 4:96 r a t i o of the (E) and (Z) hexenoates 162 and 163, respectively (equation 36). Hence the terminal bromide did not seem to in t e r f e r e with addition to the a-ynoate. - 56 -Br-(CH2),-CSC-C02Me 154 Me3SnCu-SMe2 -78°C Me,Sn Br (35) CO.Me 162 154 [Me3SnCuSPh]Li Me3Sn 162 Br CO, Me (36) 163 496 S ince the "thermodynamic" i n te rmed ia te 150 was necessary f o r i n t r a m o l e c u l a r t r a p p i n g , the (pheny l th i o ) cup ra te _14_ was chosen as the t r i m e t h y l s t a n n y l group t r a n s f e r agent. React ion of e s te r 154 w i t h the cuprate reagent _14_ (THF, -48°C, 4 h) f o l l owed by a d d i t i o n of HMPA and a l l ow i ng the r e a c t i o n mixture to warm to room temperature a f f o r d e d , a f t e r app rop r i a te workup, an o i l which con ta ined , on the bas i s of g l c (column B) a n a l y s i s , a 98:2 mixture of two products a long w i t h a number of minor (= 1%) products (equat ion 37 ) . The major product was i d e n t i f i e d as the des i red c y c l i z e d e s t e r 164 (77% y i e l d ) and the minor product as the p r e v i ou s l y prepared propenoate 94_ (Table I I I ) . S i m i l a r r e a c t i o n w i t h the iodo e s te r 155 a l so a f fo rded a 98:2 mixture of e s te r s 164 (73%y ie ld ) and 94_, r e s p e c t i v e l y , wh i l e c y c l i z a t i o n of the raesyloxy e s t e r 157 gave a 86:14 mixture (77% y i e l d of mixture ) of the same e s t e r s . - 57 -Br-(CH2),-CSC-C0aMe 154 [Me,SnCuSPh]Li THF—HMPA -48°C — rt aCO tMe Me,Sn C02Me + SnMe, (37) 164 9 4 982 The proposed s t r u c t u r e of e s t e r 164 i s i n complete agreement w i t h i t s s p e c t r a l da ta . The *H nmr spectrum of t h i s m a t e r i a l con s i s ted of a 9-proton s i n g l e t at 6 0.17 (w i th s a t e l l i t e peaks due to Sn-H coup l i n g , = 54/56 Hz ) , a 2-proton qu i n te t at 6 1.91 (J_ = 7 Hz ) , a 4-proton t r i p l e t at 6 2.63 (J_ = 7 Hz) and a 3-proton s i n g l e t at 6 3.73. These s i g na l s were r e a d i l y ass igned to the t r i m e t h y l s t a n n y l group, the n o n - a l l y l i c methylene, the two a l l y l i c methylenes and the methyl e s t e r f u n c t i o n -a l i t y , r e s p e c t i v e l y , of e s t e r 164. In a d d i t i o n , the i r spectrum of t h i s m a t e r i a l conta ined the appropr i a te bands f o r an a,6 -unsaturated e s t e r (1700, 1585 c m - 1 ) con ta i n i n g a t r i m e t h y l s t a n n y l group (770 c m - 1 ) . Formation of the unexpected e s t e r 94_ may be r a t i o n a l i z e d (Scheme 15) as o c c u r r i n g v i a format ion of the in te rmed ia te 166 which presumably i s formed by i s o m e r i z a t i o n of i n te rmed ia te 165. I n t r amo lecu l a r y - a l k y l a t i o n of i n te rmed ia te 166, which r e s u l t s i n the f a c i l e 1 * 6 c l o su re of a 3-merabered r i n g , a f f o r d s the cyclopropane 94. D i r e c t c y c l i z a t i o n of i n te rmed ia te 165 a f f o rd s the expected e s te r 164. A l t e r n a t i v e l y , the propenoate _94_ may r e s u l t from c y c l i z a t i o n of the i n te rmed ia te 165 v i a an i n t r a m o l e c u l a r p r o t o n - t r a n s f e r p roces s . - 58 -XHCH^-CsC-CCMe [Me,SnCuSPh]Li U SPh \ i c " C08Me SnMe, 165 CO,Me SnMe, 164 166 Me,Sn C02Me 9 4 Scheme 15 Attempted c y c l i z a t i o n of the next higher homolog, bromo ester 160, into the 6-raembered ring enoate 167 was not quite as s t r a i g h t -forward (equation 38). Thus, reaction of the ester 160 with the (phenylthio)cuprate _14_ under conditions used to ef f e c t c y c l i z a t i o n of 154 afforded an o i l which contained, on the basis of glc (column B) - 59 -an a l y s i s , only 3% of the desired c y c l i z e d ester 167*. Instead, the major product i s o l a t e d (43%) was an ester which was isomeric with the expected compound and was eventually i d e n t i f i e d as the a-trimethyl-stannyl enoate 168. Although the *H nmr spectrum of t h i s material was very s i m i l a r to that of ester 167, i t s d i s t i n g u i s h i n g feature was a broad t r i p l e t (J_ = 7 Hz) at 6 2.70 (which was downfield from any of the signals due to the protons of 167) a t t r i b u t a b l e to the a l l y l i c methylene protons c i s to the ester group. The *H nmr spectrum of th i s material also contained a 9-proton s i n g l e t at 6 0.24 (with s a t e l l i t e peaks due to Sn-H coupling, J_ = 53/56 Hz), a 4-proton multiplet around 6 1.6, a broad 2-proton t r i p l e t at 6 2.38 and a 3-proton s i n g l e t at 6 3.70. These signals were r e a d i l y assigned to the trimethylstannyl group, the two ring methylenes, the remaining a l l y l i c methylene (trans to the ester group), and the methyl ester moiety, respectively. The i r spectrum was also consistent with the presence of an a,S-unsaturated ester (1700, 1600 cm - 1) function and a trimethylstannyl group (775 cm - 1). Also i s o l a t e d (19% y i e l d ) was the bis(trimethylstannyl) ester 169. In l i g h t of our previous work with a l k y l (E)-2,3-bis(trimethyl-stannyl)-2-alkenoates (115), i d e n t i f i c a t i o n of t h i s compound was quite routine. In p a r t i c u l a r , the 1H nmr spectrum of ester 169 showed the two h i g h - f i e l d 9-proton si n g l e t s (at 6 0.17 and 0.26) along with associated * Previously prepared i n our laboratories by A. Tse via reaction of the (phenylthio) cuprate J_4_ with l-carbomethoxy-2-(p-toluenesul-fonyloxy)-l-cyclohexene. - 60 -s a t e l l i t e peaks due to Sn-H coupling (Jj3n_H = 5 4 H z ) c h a r a c t e r i s t i c of esters 115. In addition, the p o s i t i o n of the s i g n a l due to the y-protons (6 2.51) was consistent with the assigned stereochemistry (see Table V). 160 CO,Me SnMe, 168 [Me,SnCuSPh]Li Me,Sn COaMe Br-(CH a l-C«C-CO,Me - V V JCQ THF-HMPA B r ^ ^ ^ / \ , 0 5 , ( 3 8 ) -48°C—rt SnMe, + aCOaMe SnMe, 167 C y c l i z a t i o n of the iodo ester 161 under the same conditions as those used for c y c l i z a t i o n of the bromo ester 160 (equation 38) also did not afford an appreciable amount of the desired ester 167. Analysis of the product mixture by glc (column B) indicated that the major product was the ester 168 while only small (= 5%) amounts of the desired ester 167 were present. Thus, although c y c l i z a t i o n to form the 5-merabered ring ester 164 proceeded r e l a t i v e l y smoothly, analogous formation of the 6-raembered ri n g ester 167 did not. Formation of compound 168 may be r a t i o n a l i z e d as follows (Scheme 16). We have previously obtained evidence for the - 61 -r e v e r s i b i l i t y of the addition of (trimethylstannyl)copper reagents to 44 a,8-acetylenic esters . Hence i t i s reasonable to propose that addition of cuprate 14 to ester 160 (reaction A) i s r e v e r s i b l e . We have also previously observed the formation of small amounts of ct-trimethyl-47 stannyl-ct, 8-unsaturated esters from a,8-acetylenic esters. Thus the reve r s i b l e formation of intermediate 171 by a-addition of the cuprate Br-(CHt)4-CSC-C0,Me 160 14 A C 170 B 171 167 D 168 Scheme 16 - 62 -reagent _14_ (reaction C) i s not u n r e a l i s t i c . If c y c l i z a t i o n to form the desired 6-membered ring ester 167 (reaction B) i s much slower than c y c l i z a t i o n to form the 5-membered ring ester 168 (reaction D), and i f both c y c l i z a t i o n s are i r r e v e r s i b l e , then the materials would be funneled ( v i a e q u i l i b r i a A and C) towards ester 168, which i s the major product observed. The bis(trimethylstannyl) ester 169 presumably re s u l t s from coupling of the intermediate 170 with excess (trimethylstannyl)cuprate 14. II. Preparation of the Acyl Portion of Trlophamine, a Unique Diacylguanidine from the Dorid Nudibranch Trlopha catalinae (Cooper) A. Introduction During the course of our work, Gustafson and Andersen 4 8 i s o l a t e d a novel diacylguanidine from skin extracts of Triopha c a t a l i n a e . They reported the structure as 172 with the stereochemistry of the carbon-carbon double bonds not defined. Considering the structure of trlophamine, the p o s s i b i l i t y of synthesizing t h i s natural product presented an excellent opportunity for u t i l i z i n g some of the methodology described above. Also, a synthesis of trlophamine would confirm the s t r u c t u r a l e l u c i d a t i o n work and e s t a b l i s h the stereochemistry of the carbon-carbon double bonds. Since our previous work had focussed on the formation of s t e r e o c h e m i c a l ^ well-defined v i n y l l i t h i u m reagents, we - 63 -f e l t that the synthesis of the acyl portion of triophamine would be a straightforward extension of our in v e s t i g a t i o n s . It seems clear that the f i n a l stages of a t o t a l synthesis of (±)-triophamine would involve the condensation of guanidine with a suitable derivative of one of the carboxylic acids 173 or 174. Therefore, the f i r s t objective was the synthesis of one (or both) of these acids. Although many retrosynthetic disconnections of 173 and 174 are possible, the plan shown in Scheme 17 was chosen. Thus, h e t e r o l y t i c cleavage of the C-3 - C-4 bond i n 173 affords, as one p o s s i b i l i t y , the donor synthon 175 and the acceptor synthon 179. From a synthetic point of view, then, the acid 173 could be prepared by conjugate addition of a stereochemically homogeneous organometallic reagent 176 [M=Li, Cu(Y)Li, etc. ] to a suitable derivative of 2-ethylpropenoic acid 180. Analog-ously, use of the organometallic reagent 178 would a f f o r d , a f t e r appropriate functional group manipulation, the acid 174. The organo-m e t a l l i c reagents 176 and 178 should, In turn, be r e a d i l y available from the (Z) and (E)-3-(tri-n-butylstannyl)-2-pentenoates (183) and (184), respectively, compounds somewhat f a m i l i a r to us. 172 - 64 -173 174 M 176 177 + 179 178 180 S cheme 17 B. Preparation of (Z)-173 and (E)-2,4-diethyl-4-hexenoic acid (174) In our prev ious work i n v o l v i n g the use of ( t r i a l k y l s t a n n y l ) c o p p e r reagents , we had used nea r l y e x c l u s i v e l y t r i m e t h y l s t a n n y l compounds. We have used these d e r i v a t i v e s mainly f o r convenience. Thus, the r e l a t i v e s i m p l i c i t y of the *H nmr spec t ra of t r i m e t h y l s t a n n y l compounds makes - 65 -i n t e r p r e t a t i o n easier while the v o l a t i l i t y of tetramethyltin and hexamethylditin makes p u r i f i c a t i o n of products easier. However, since the trimethylstannyl alkenes 176 and 178 (M=SnMe3) would probably be quite v o l a t i l e , we chose to use the corresponding t r i - n - b u t y l s t a n n y l d e r i v a t i v e s in the present study. Reaction of ethyl 2-pentynoate _53_ with l i t h i u m (phenylthio)-(tri-n-butylstannyl)cuprate (181) (THF, -48°C), followed by appropriate workup and chromatographic p u r i f i c a t i o n of the crude product, afforded et h y l (Z^)-3-(tri-n-butylstannyl)-2-pentenoate (183) (76%) (Scheme 18). On the other hand, reaction of 53 with the (tri-n-butylstannyl)copper reagent (182) (THF, -78°C) afforded the corresponding geometric isomer 184 (83%). The xbl nmr spectra of these two esters f u l l y corroborated the stereochemical assignments. Thus the y p r o t o n s of compound 183 give r i s e to a doublet of quartets (J_ = 7.5, 1.5 Hz) at 6 2.42 while the analogous protons of compound 184 produce a signal at 6 2.88. It seems reasonable, therefore, to conclude that the v i n y l ethyl group i s c i s to the ester moiety i n isomer 184. Moreover, i n compounds such as 183 and 184, the magnitude of the coupling constants associated with the coupling of the alkene proton with the t i n nuclei ( 1 1 7 S n and 1 1 9 S n ) i s stereochemically diagnostic. It i s k n o w n 1 ° c that when the t r i a l k y l s t a n n y l group and the v i c i n a l alkene proton are i n a trans r e l a t i o n s h i p , J$n-H - 120 Hz while t h i s value i s = 70 Hz when these groups are c i s to one another. In compounds 183 and 184, the values of Jg n_H are 109 and 65 Hz, r e s p e c t i v e l y . - 66 -- 67 -The ester 183 was reduced to the alkene 187 v i a a two-step sequence as follows. Reduction of the ester 183 with diisobutylaluminum hydride afforded the alcohol 185 (90%). Subsequent treatment of t h i s material with p y r i d i n e - s u l f u r t r i o x i d e complex i n THF followed by 4 9 reduction of the intermediate s u l f a t e with lithium aluminum hydride gave (Z)-3-(tri-n-butylstannyl)-2-pentene (187) i n 87% y i e l d . The preparation of the vinylstannane 187, the immediate precursor to the v i n y l l i t h i u m reagent 189, was thus achieved. Transmetalation (n-butyl-lithiura, THF, -20°C) of compound 187, followed by treatment of the intermediate v i n y l l i t h i u m species with a number of copper sources (e.g. 2 2 phenylthiocopper , cuprous bromide-dimethylsulfide complex followed by t r i - n - b u t y l p h o s p h i n e 5 0 , or boron t r i f l u o r i d e e t h e r a t e 5 1 , and 5 2 3,3-dimethyl-l-butynylcopper ) produced the expected cuprate or copper species 176 (M=CuYLi). Unfortunately, conditions to e f f e c t addition of these l a t t e r intermediates to ethyl 2-ethylpropenoate ( 1 9 4 ) 5 3 could not be found. In general, the v i n y l cuprates 176 (M=CuYLi) were not very thermally stable. At low temperatures ( t y p i c a l l y <-48°C), they did not couple with the a,B-unsaturated ester 194 while at higher temperatures 54 they decomposed. In t h i s connection, the recent report by Lipshutz (not available u n t i l a f t e r the present work was completed) that mixed cuprates R 2Cu(CN)Li2 add well to enoates might be quite u s e f u l . Eventually, i t was found that treatment of the v i n y l l i t h i u m species 189 (THF, -78°C) with the N,N',N'-trimethylhydrazide of 2-ethylpropenoic 55 acid (191) provided, in addition to small amounts of the s t a r t i n g materials 187 and 191, the adduct 192 (42% y i e l d ) . - 68 -Hydrolysis of the trimethylhydrazide 192 proved to be somewhat problematic. Thus, treatment of compound 192 with hot d i l u t e hydro-c h l o r i c acid for 2 h cleanly converted t h i s material not into the desired acid 173 but into 2,4,4-triethylbutyrolactone (195) (78% y i e l d , equation 39), a product a r i s i n g from p a r t i c i p a t i o n of the carbon-carbon double bond i n the hydrolysis process. Although the *H nmr spectrum of th i s material was not very informative (other than to show that no o l e f i n i c protons were present), the i r spectrum indicated that the product was a 5-membered ring lactone (1770 cm - 1). Use of weaker acids (39) 192 195 (Dowex-50, oxa l i c acid or ac e t i c acid) also resulted i n the formation of the lactone 195. Attempted base hydrolysis of 192 under a number of reaction conditions (e.g. 40% NaOH in ethylene g l y c o l , 140°C, 16 h; saturated NaOH i n hexamethylphosphoramide, 100°C, 60 h; Na 20 2, 60°C, 2 56 57 h ) returned only s t a r t i n g material. Oxidative cleavage (lead tetraacetate, eerie ammonium n i t r a t e ) lead to a potpourri of products. It was found ultimately that the trimethylhydrazide 192 could be converted into the desired acid 173 by treatment of the former substance with diisobutylaluminum hydride (1.1 equivalents, ether, 0°C), followed by oxidation of the resultant crude product with pyridinium dichromate - 69 -i n dimethylformaraide . The p u r i f i e d product, (Z)-2,4-diethyl-4-hexenoic acid (173), was obtained i n 50% y i e l d based on unrecovered 192, and provided spectra ( i r , *H nmr) which were very s i m i l a r to, but c l e a r l y d i f f e r e n t from, those of the carboxylic acid obtained by hydrolysis of natural triophamine. Presumably, therefore, the carbon-carbon double bond of the acyl residues of triophamine possesses an (E) rather than a (Z) configuration. The required (E) carboxylic acid 174 was prepared v i a a route i d e n t i c a l with that described for the (Z) acid 173. Thus, conversion of the ester 184, v i a the alcohol 186 and the vinylstannane 188, into (Z^-3-lithio-2-pentene (190), followed by conjugate addition of the l a t t e r reagent to compound 191, afforded the o l e f i n i c trimethylhydrazide 193. Subjection of this material to the reduction-oxidation sequence described for the conversion of 192 into 173 afforded the carboxylic acid 174, which gave spectra ( i r , nmr) i d e n t i c a l with those of the natural acid derived from triophamine. C. Synthesis of triophamine and i t s diastereomer The carboxylic acid 174 was subsequently converted into triopha-mine and i t s diastereomer by Andersen and G u s t a f s o n 5 9 as follows (equation 40). Treatment of the acid 174 with p-nitrophenol i n the presence of N,N'-dicyclohexylcarbodiimide afforded the _p_-nitrophenyl ester 196. Condensation of this activated ester with guanidine under c a r e f u l l y monitored conditions provided a chromatographically separable mixture of (±)-triophamine (172) and the expected diastereomer. The - 70 -former product gave spectra ( i r , H nmr) i d e n t i c a l with those of the natural product. 174 R = H 196 R « p - C , H 4 N 0 2 Thus the short synthesis described above corroborates the previous s t r u c t u r a l e l u c i d a t i o n work on trlophamine and establishes the configuration of the o l e f i n i c double bonds present i n th i s unusual natural product. Furthermore, we have shown that isomeric, stereo-c h e m i c a l ^ homogeneous v i n y l l i t h i u r a reagents, such as 189 and 190, may be re a d i l y prepared from a,B-acetylenic esters v i a the stereoselective synthesis of 8-trialkylstannyl-a,8-unsaturated esters. This type of methodology should be useful for the synthesis of carbon-carbon double bonds of s p e c i f i c configuration i n other natural products. III . Reaction of (Trimethylstannyl)copper Reagents with g,B-Acetylenic N,N-Dimethylamldes A. Preparation of g,8-acetylenic N,N-dlmethylamldes We have also investigated the reaction of a number of (trimethylstannyl)cuprate reagents with a,8-acetylenic N,N-dimethyl-Table VII. Preparation of a,8-acetylenic N,N-dimethylamides. 1) MeLi R-C5C - H 47 2) CI-CONMe a R-C=C-CONMe 197 z Entry Alkyne R Product Y i e l d (%) a 1 50 Me 200 81 2 52 Et 201 85 3 56 2-(2-cyclopentenyl)ethyl 202 77 4 198 t-BuMe 2Si0(CH 2)3 203 92 5 199 t-Bu 204 95 a Y i e l d of p u r i f i e d , i s o l a t e d product. - 72 -amides. Although previous studies had shown that a,8-acetylenic esters reacted smoothly with these cuprate reagents, i t was of i n t e r e s t to determine (a) how the r e a c t i v i t y of the amides might d i f f e r and (b) i f the products could be transmetalated d i r e c t l y or transformed into s y n t h e t i c a l l y useful functionalized vinylstannanes. The required acetylenic amides 197 were r e a d i l y prepared by successive treatment of the corresponding 1-alkyne (47) with methyl-lithium and N,N-diraethylcarbamoyl chloride (Table VII). Although the r e s u l t s shown in Table VII are la r g e l y self-explanatory, i t should be noted that, although the reactions were a l l quite clean, i t was often best to hydrolyze excess N,N-dimethylcarbamoyl chloride (lachrymatory, mutagenic) with aqueous sodium bicarbonate prior to i s o l a t i o n of the desired amide. The amide 197 could then be p u r i f i e d by simple d i s t i l -l a t i o n . B. Preparation of (Z)-and (E)-N,N-dimethyl-3-trimethylstannyl-2—alkenamldes With a number of a,8-acetylenic N,N-dimethylamides i n hand, we set out to examine the i r reactions with some (trimethylstannyl)copper reagents. It had been shown e a r l i e r that reaction of lithium (phenyl-thio)(trimethylstannyl)cuprate (14) with e t h y l 2-pentynoate (53) in THF at -78°C for 3 h afforded a mixture of the (E) and ( Z ) pentenoates B9 26 and 90, in a r a t i o of 68:32, respectively (equation 41) . In contrast, reaction of N,N-dimethyl-2-butynamide (200) under the same conditions - 73 -gave (76% y i e l d ) a s i n g l e product. I n t e r p r e t a t i o n of the r e l a t i v e l y s imple h nmr spectrum of t h i s m a t e r i a l i n d i c a t e d that i t was (E ) -N,N-d imethy l - 3 - t r imethy l s t anny l - 2 -bu tenamide (205) (equat ion 42) . Thus, i M P Sn Me.Sn COaEt [Me,SnCuSPh]Li Me,Sn Et-CSC-C02Et * }=\ + (41) . Et C02Et E t c « -78C,3h 5 3 8 9 9 0 6832 [Me3SnCuSPh]Li M e » S n Me-C5C-C0NMe2 - ^ *" Me CONMe2 (42) 2 0 0 -78°Cor-48'C a 9-proton s i n g l e t at 6 0.15 (w i t h s a t e l l i t e peaks due to Sn-H c o u p l i n g , £ = 52/55 Hz ) , a 3-proton doublet at 6 2.02 (J_ = 2 Hz) and two 3-proton s i n g l e t s at 6 2.98 and 3.00 i n d i c a t e d the presence of a t r i m e t h y l s t a n n y l group, a v i n y l methyl group, and a dimethylamide moiety , r e s p e c t i v e l y . A s i n g l e v i n y l proton s i g n a l at 6 6.07 served to i d e n t i f y the s t e r e o -chemistry as (E) ; s ince Jsn-H w a s 7 ^ 1 1 2 ' t n e t i n a t o m a n d t h e hydrogen must have been c i s 1 ° c . The i n f r a r e d spectrum cor roborated the s t r u c t u r a l assignment; bands at 1630 and 780 c m - 1 cou ld be a s c r i bed to the carbony l s t r e t c h i n g v i b r a t i o n of a t e r t i a r y amide group and to the Sn-Me rock i ng of a t r i m e t h y l s t a n n y l group, r e s p e c t i v e l y . - 74 -Reaction of the a,8-acetylenic amide 200 with the cuprate reagent 14 under conditions (THF, -48°C) which transformed the a,8-acetylenic ester _53_ almost excl u s i v e l y into the (Z) unsaturated ester 90_ also afforded only the (E) unsaturated amide 205 (equation 42). These r e s u l t s are consistent with the findings of Henrick and his co-workers i n th e i r work on the addition of dialkylcuprates to 21 at, 8-acetylenic amides . For example, they found that lithium diethylcuprate added to l-(2-butynoyl)pyrrolidine (206) (ether, -78°C) to give the unsaturated amide 207 with 99% s t e r e o s e l e c t i v i t y (equation 43). In comparison, the addition of lithium di-n-butylcuprate to methyl 2-butynoate (72) under the same reaction conditions gave a 74:26 mixture of the stereoisomeric esters 73_ and 74, respectively (equation 17). Thus, there are d e f i n i t e l y p a r a l l e l s between the reactions of Q-ButCuLi Q-BU G-Bu CO, Me Me-CEC-CO,Me + Me (17) 72 73 74 Me-CSC-CON 2 0 6 Et.CuLi Ether . -73°C (43) - 75 -(trimethylstannyDcopper reagents with a, B-acetylenic esters and amides and the reactions of alkylcopper reagents with these substrates. However, there have been no reports to date of a stereoselective trans-addition of a cuprate reagent to an a,B-acetylenic amide. Various reaction conditions were explored in attempts to form the geometric isomer of the unsaturated amide 205. Eventually, i t was found that the addition of a less polar solvent (hexanes or ether) to the reaction medium along with an increase in reaction temperature (0°C) lead to the stereoselective formation of the (Z^ unsaturated amide 208. Thus, reaction of the acetylenic amide 200 with the cuprate reagent 1_4_ i n THF at -48°C, followed by addition of dry ether and slow warming of the reaction mixture to 0°C gave, af t e r appropriate workup, a mixture of the (Z) and (E_) unsaturated amides 208 and 205 i n a r a t i o of 95:5, respectively (equation 44). The (Z) compound, i s o l a t e d by column chromatography of the mixture, was obtained as white needles (mp 49-50°C). The *H nmr spectrum of t h i s material was very s i m i l a r to that of the (E_) isomer 205. As i n the case of amide 205, the signal due to the v i n y l proton was invaluable in the assignment of stereochemistry. Thus, the quartet at 6 6.85 (J_ = 2 Hz) had s a t e l l i t e peaks due to Sn-H coupling with Jg n-H = 124 Hz, which i s i n d i c a t i v e of a v i c i n a l trans r e l a t i o n s h i p between the t i n atom and the v i n y l proton. The i n f r a r e d spectrum (KBr) of amide 208 did not exhibit a band c h a r a c t e r i s t i c of a t e r t i a r y amide (~ 1630 cm - 1) but rather exhibited a band at 1730 cm - 1. This d r a s t i c s h i f t in the carbonyl stretching frequency of the amide f u n c t i o n a l i t y i n the (Z) isomer 208 may be r a t i o n a l i z e d by invoking coordination of the amide nitrogen to the t i n atom i n the s o l i d state. The corresponding band of the same compound in chloroform solution was found at 1625 cm - 1, a much more ty p i c a l value. [Me,SnCuSPh]Li Me,Sn CONMe, Me3Sn Me-CSC-CONMe 2 T H F - E t h e r + Me (44) CONMe, 2 0 5 Me 2 0 0 -48°C — 0°C 2 0 8 95:5 It was necessary to add ether (or a hydrocarbon solvent) to the reaction medium to promote formation of the (Z) isomer 208; when the reaction was allowed to proceed in THF for 6 h at -20°C without the addition of ether, only 7% of (20 isomer 208 was detected. Analogous solvent effects have been reported for the addition of alkylcuprate 21 3 5 reagents to a,6-acetylenic esters » . For example, the addition of lithium di-n-butylcuprate to methyl 2-butynoate at -78°C i n THF afforded a 97:3 mixture of the (E) and (Z) isomers 73_ and 7_4, respectively, while reaction in ether provided a 74:26 mixture, respectively (equations 17, 45) . The cause of this solvent effect i s not clear but may be related to the rela t i v e Lewis base strengths of ether and THF. If one represents the presumed intermediates in the reaction of the cuprate reagent _14_ with dimethylamides 197 as structures 209 and 210 (although the actual structures are probably oligomeric), the (E) amides would result from protonation of intermediate 209 while the isomeric (Z) - 77 -0-ButCuU D-Bu O-Bu CO.Me Me-CEC-COtMe + Me CO.Me 72 73 74 74 26 (17) THF, -78C 97 3 (45) amides would ar i s e from protonation of intermediate 210. Formation of (Z_) amides would thus occur only i f the intermediate 209 isomerizes to intermediate 210. In a solvent with better coordinating a b i l i t y (THF) the intermediate 209 i s conf i g u r a t i o n a l l y more stable than when the solvent i s not as basic. It i s not obvious whether t h i s e f f e c t i s due to e f f e c t s on the strength of the C-Cu bond ( i f one exis t s ) i n i n t e r -mediate 209, changes i n the oligoraeric structure of 209, or due to other less-obvious f a c t o r s . It i s also not obvious why the intermediate 209, formed i n the addition of the cuprate reagent _14_ to a, 8-acetylenic amides, i s more con f i g u r a t i o n a l l y stable than the corresponding intermediate 212 formed from a,8-acetylenic esters. One possible explanation i s that the amide intermediate, due to better resonance s t a b i l i z a t i o n , i s less l i k e l y to isomerize to the a l l e n i c enolate 211, which may be the "thermodynamic" intermediate or may be involved i n the rearrangement of 209 to 210. This argument i s consistent with the observation that the addition of alkylcuprate reagents to a,B-acetylenic ketones, which would give an - 78 -intermediate that should more r e a d i l y form an a l l e n i c enolate, i s more d i f f i c u l t to control stereochemically than i n the case of 60 a,8-acetylenic esters . SPh Me3Sn Cu-Li X R CONMe2 2 0 9 Me,Sn C0NMe2 R Cu-Li SPh 210 Me3Sn SPh OCu-Li R NMe2 211 SPh i Me3Sn Cu-Li R C02R' 212 As pointed out previously i n connection with a discussion concerning the possible intermediates derived from a,8-acetylenic esters (section I,C), i t may well be that, although the i n i t i a l intermediate derived from addition of the cuprate reagent _14_ to acetylenic amides 197 may be represented by 209, isoraerization of t h i s intermediate gives r i s e to another Intermediate better represented by the a l l e n i c structure 211. Thus, i t would then be protonation of th i s intermediate 211 which would afford (Z)-8-trimethylstannyl-a,8-unsaturated amides. A number of other a,8-acetylenic N,N-diraethylamides (197) were allowed to react with the cuprate reagent _14_ under conditions i d e n t i c a l - 79 -with those used to prepare the unsaturated amides 205 and 208. The re s u l t s are summarized i n Table VIII. It can be seen that, i n general, reaction of the amides 197 with the cuprate reagent _L4. proceeded smoothly at low temperatures (-78°C) i n THF to afford only the (E) isomer 213 while reaction i n THF-ether (1:2) at higher temperatures (-20°C-0°C) gave predominantly the (Z) isomer 214. The only exceptional case encountered was, not unexpectedly, with N,N,4,4-tetraraethyl-2-pentynamide (204). This amide, l i k e the corresponding ester 103, reacted very slowly with the (phenylthio)-cuprate lb_ i n THF at -78°C; an excess (3 equiv.) of reagent along with higher temperatures and longer reaction times (-48°C, 12 h) were required before the reaction proceeded to completion. In t h i s case (equation 46), the isomeric amides 221 and 222 were produced i n a r a t i o of 88:12, respectively. This result i s i n contrast to that obtained with the ester case i n which we were unable to e f f i c i e n t l y prepare the (E) isomer 104 (equation 47), and i s a d d i t i o n a l evidence that the amide intermediate 209 i s c o n f i g u r a t i o n a l l y more stable than the corresponding ester intermediate 212. The assignments of stereochemistry were based, as i n the case of butenamides 205 and 208, on *H nmr spectroscopy. Thus, the a-protons of the (Z) isomers 214 i n v a r i a b l y gave r i s e to signals i n t h e i r *H nmr spectra which showed Jj5n-H ~ 120 ^ while the corresponding protons of the (E) isomers gave r i s e to signals which indicated J_Sn-H ~ 70 Hz. In contrast to the isomeric esters 2l_ and 22_, there was not an appreciable difference in the chemical s h i f t of the Y -P r°tons of the - 80 -Table V I I I . React ion of l i t h i u m ( p h e n y l t h i o ) ( t r i m e t h y l s t a n n y l ) c u p r a t e (14) w i t h a , B - a c e t y l e n i c N,N-dimethylamides. [Me,SnCuSPh]Li Me,Sn Me,Sn CONMe2 R-CSC-CONMe2 — \—> + y=/ ^gj R CONMe2 R 213 214 Entry Alkynamide R Conditions 3 Products 213:214b Yield (%) c 1 200 Me A 205: 208 >99:<1 76 2 200 Me B 205: 208 5:95 68 3 201 Et A 215: :216 >99:<1 81 4 201 Et B 215: :216 4:96 73 5 203 £-BuMe2S10(CH2)3 A 217: :218 >99:<1 76 6 203 _t-BuMe2S10(CH2)3 B 217; :218 5:95 76 7 202 2-(2-cyclopentenyl)ethyl A 219: :220 >99:<1 76 8 202 2-(2-cyclopentenyl)ethyl B 219: :220 7:93 72 9 204 _t-Bu C 221: :222 88:12 69 10 204 t-Bu D 221: :222 5:95 72 a Cond i t i ons were A: 1.5 equ iv . of _14, THF, -78°C, 3 h. B: 1.5 equ iv . of _14, THF, -48°C, 1 h then ether (2 volumes), -48°C, 1 h; -20°C, 1 h; 0°C, 2 h. C: 3.0 equ iv . of 14_, THF, -48°C, 12 h. D: 3.0 equiv. of 14_, THF, -48°C, 6 h then ether (2 volumes), -48°C, 1 h; -20°C, l h ; 0°C, 3 h. D As determined by g l c (column A) a n a l y s i s . c Y i e l d of i s o l a t e d , p u r i f i e d product a f t e r chromatography. - 81 -i s omer i c amides 213_ and 214. For example, the y -protons of the pentenamides 219_ and 220 gave r i s e to s i g na l s at 6 2.45 and 6 2.44, r e s p e c t i v e l y . u~ <s„ Me,Sn C0NMe 2 [Me,SnCuSPh]Li Me3Sn \ / t-Bu-CSC-C0NMe2 " y=\ + (46) - 4 8 ° C , 1 2 h C0NMe 2 "A 2 0 4 221 2 2 2 88-12 t-Bu-C=C-C02Et 103 [Me,SnCuSPh]Li Me,Sn M e » S n ^ C 0 , E t ~y\ C0 2Et " A (47) -78°C . 6h 104 105 8 92 Although *H nmr spectroscopy d e f i n i t i v e l y showed the s t e r e o -chemist ry of the i s omer i c amides 213 and 214, t h e i r chromatographic behaviour was qu i t e u s e f u l i n p r e l i m i n a r y specu l a t i on s on the s t e r e o -chemical outcome of the r e a c t i o n s . More e x p l i c i t l y , the (Z) unsaturated amides 214 c o n s i s t e n t l y showed g rea te r m o b i l i t i e s on t i c analyses ( s i l i c a g e l , development w i t h petroleum e t h e r - e t h e r m ix tu res ) and sho r te r r e t e n t i o n times on g l c analyses (columns A and B) than the corresponding (E) amides 213. Thus, one may make reasonably con f ident t e n t a t i v e assignments of s te reochemis t ry f o r any i s omer i c p a i r of amides 213 and 214 s imply by g l c or t i c . A s i m i l a r ob se rva t i on was made i n the e s t e r s e r i e s : On t i c ana ly ses , the (Z) e s t e r 22_ c o - e l u t e d w i t h the - 82 -bis(trimethylstannyl) ester 115, ahead of the (E_) ester 2l_, while on g l c analyses the order of e l u t i o n was (Z) ester 22_, (E_) ester 21, and, f i n a l l y , bis(trimethylstannyl) ester 115. Me,Sn Me,Sn COtR' Me3Sn COaR' X _ .X R xSnMe. R C02R' H oo 21 2 2 Addition of the (trimethylstannyl)copper reagent (44) to a,B-acetylenic amides also proceeded with high s t e r e o s e l e c t i v i t y . Some of the r e s u l t s obtained are shown in Table IX. As in the case of the reaction of t h i s reagent with a, 8-acetylenic esters, only the (E) isomers were formed at low temperatures (-48°C) i n THF. This was not at a l l s u r p r i s i n g since the (phenylthio)cuprate the reagent of choice for the formation of (Z) esters 22, also gave only the (E_) isomers under the same reaction conditions. No attempt was made to form the (Z) amide 214 using the copper reagent 44. The (cyano)cuprate 46_ reacted cleanly with N,N-dimethyl-2-butynamide (200) (THF, -48°C) to afford e x c l u s i v e l y the (E) adduct 205 i n excellent y i e l d (equation 48). However, attempted reaction of t h i s reagent with the homologous amide 201 under the same conditions returned mostly s t a r t i n g material (equation 49). It was noted that in the former case the reaction mixture changed from orange to yellow within minutes of addition of the substrate while i n the l a t t e r case, the color - 83 -Table IX. Reaction of the (trimethylstannyl)copper reagent (44_) with a ,8-acetylenic N,N-dimethylamides. Me,SnCu-SMe2 Me.Sn R-C=C-CONMe 2 — 7 = \ THF -78 C / \ R CONMe 2 197 213 Entry Alkynamide R Product Y i e l d (%) 1 200 Me 205 83 2 201 Et 215 91 3 202 2-(2-cyclopentenyl)ethyl 219 80 4 203 t-BuMe 2SiO(CH 2)3 217 77 a Y i e l d of i s o l a t e d , p u r i f i e d product. - 84 -remained bright orange for the duration of the reaction. Reaction of the pentynamide 201 with the (cyano)cuprate 46_ proceeded to completion when the reaction mixture was warmed to 0°C ( a f t e r the addition of HMPA) to give an 88:12 mixture of the (E) and (Z) pentenamides 215 and 216, resp e c t i v e l y (equation 50). Hence i t seems that the (cyano)cuprate 46 i s less reactive towards a,6-acetylenic amides 197 when R=Et than when R=Me. We have previously noted a p a r a l l e l d i f f e r e n c e with a,B-acetylenic esters. Me-CSC-CONMe, 2 0 0 [Me,SnCuCN]Li Me,Sn THF. -48°C M e CONMe, 2 0 5 (48) Et-CSC-CONMe 2 201 Me,Sn K Et CONMe a 215 4 9 6 201 (49) 201 [Me,SnCuCN]Li THF—HMPA, -48'C—0C 215 Me,Sn CONMe W Et (50) 216 8812 While the (cyano)cuprate 6^_ exhibited d i f f e r e n t i a l r e a c t i v i t y with d i f f e r e n t acetylenic amides 197, both the (trimethylstannyl)copper - 85 -reagent (44) and the (phenylthio)cuprate _14_ reacted smoothly with a number of acetylenic amides (Tables VIII, IX) i n e s s e n t i a l l y the same manner i n which they reacted with N,N-dimethyl-2-butynamide (200). Thus, by the appropriate choice of reagent and reaction conditions, we have been able to obtain, highly s t e r e o s e l e c t i v e l y , e i t h e r the (_E) amide 213 or the (Z) amide 214. When the acetylenic amide 197 was allowed to react with either the copper reagent _44_ or the (phenylthio)cuprate lh_ i n THF at low temperature (-78°C), the (E_) amide 213 was the exclusive product. On the other hand, reaction with the (phenylthio)cuprate _14_ i n THF-ether at higher temperatures (-20°C-0°C) afforded predominantly the (Z) isomer 214. C. Trapping of the intermediate with electrophiles other than proton In contrast to attempts at trapping the intermediate derived from the addition of (trimethylstannyl)copper reagents to a,B-acetylenic esters, attempts at trapping the intermediate 223, which was obtained i n the addition of (trimethylstannyl)copper reagents to a,B-acetylenic amides 197, were somewhat successful (equation 51). For example, reaction of N,N-dimethyl-2-butynamide (200) with the (trimethylstannyD-copper reagent (44) (THF, -78°C) followed by the addition of HMPA and iodoraethane and allowing the reaction mixture to warm to room tempera-ture gave, a f t e r appropriate workup, the methylated amide 225 as e s s e n t i a l l y the only product (87% y i e l d , equation 52). Reactions involving the use of other reactive halides and other a,B-acetylenic amides 197 also proceeded smoothly to afford the trapped products i n - 86 -good y i e l d s (Table X ) . However, attempted r eac t i on s w i t h a l e s s r e a c t i v e pr imary i od i de (e .g . l - i odo-3 -methy lbutane) and a pr imary mesylate (e .g . 1-mesyloxyheptane) only gave the corresponding protonated compound 213 (= 224, Y=H). [Me,SnCuZ]Li R-C=C-CONMe a 197 z Me,Sn Cu-Li w R CONMe 2 223 Me,Sn M ( 5 1 ) R CONMe 2 224 1) Me 3SnCu-SMe 2 Me,Sn Me (52) Me-CSC-CONMe 2 " 2) Mel/HMPA M e CONMe 2 2 00 -78C —rt 225 The in te rmed ia te der i ved from the a d d i t i o n of the (cyano)cuprate 46 to the butynamide 200 could a l s o be trapped w i t h r e a c t i v e h a l i d e s . In these cases, however, the products a l s o conta ined a sma l l amount (= 3%) of the protonated amide 205 (= 224, R = Me, Y = H) . No attempts were made to t rap the in te rmed ia te s de r i ved from r e a c t i o n of t h i s cuprate w i t h other a , B - a c e t y l e n i c amides s ince only the butynamide 200 reacted complete ly w i t h t h i s cuprate at low temperatures. When the in te rmed ia te de r i ved from the a d d i t i o n of the (pheny l -t h i o ) c u p r a t e 1_4_ to the butynamide 200 was t r ea t ed w i t h an excess of iodomethane, the major product obta ined was t h i o a n i s o l e . A l s o present - 87 -Table X. Trapping of the intermediate derived from addition of the (trimethylstannyl)copper reagent (44) to a,8-acetylenic amides (197) with e l e c t r o p h i l e s ( Y + ) . R - C 5 C - C 0 N M e a  2) Y - HMPA 197 -7ffC— rt 1) Me,SnCu-SMea Me,Sn Y R CONMe a 224 Entry Alkynamide R Y+ Product (224) Y i e l d ( % ) a 1 200 Me M e l b 225 87 2 200 Me a l l y l bromide*5 226 82 3 200 Me methallyl iodide 227 81 4 200 Me di m e t h y l a l l y l bromide^ 228 78 5 201 Et M e l b 229 77 6 201 Et a l l y l bromide*5 230 79 7 201 Et methallyl iodide 231 77 8 202 R e M e l b 232 78 a Y i e l d of d i s t i l l e d , chromatographed material. k 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. c This material was kindly supplied by I.D.Ruckling of our laboratories who prepared i t by the method of Sarett ; the c o l o r l e s s l i q u i d was stored at -10°C over 3A molecular sieves and copper powder. d This material was not passed through basic alumina; i t was d i s t i l l e d immediately before use. e R = 2-(2-cyclopentenyl)ethyl. - 88 -i n the product mixture were the protonated amide 205 and the methylated amide 225 in a r a t i o of 5:95, r e s p e c t i v e l y . Because of the large amount of material a r i s i n g from transfer of the phenylthio group, further reactions with the (phenylthio)cuprate 14_ were not investigated. Although the spectral data of the amides 224 are in accord with the assigned structures, the stereochemistry about the double bond has not been rigorously established. Since no a-protons are present i n amides 224, the stereochemistry could not be interpreted on the basis of Sn-H coupling constants, and since the y~protons of the isomeric amides 213 and 214 do not give r i s e to appreciably d i f f e r e n t *H nmr chemical s h i f t s , an assignment based on such differences could not be made. However, i t i s very l i k e l y that the amides 224 possess the (E) configu-r a t i o n as shown since we have previously observed that the intermediates 223 isomerize only very slowly under s i m i l a r reaction conditions even when Z = SPh. Other i n d i r e c t evidence i s the chromatographic behaviour of the amides 224. On t i c analyses, the compounds show s l i g h t l y higher m o b i l i t i e s than the corresponding (E_) amides 213 but run well below the (Z) amides 214. Also, f a i r l y convincing i n d i r e c t evidence was obtained through e f f o r t s to prepare a,8-bis(trimethylstannyl)-a,8-unsaturated amides 233. Me,Sn CONMe, R SnMe, 2 3 3 - 89 -When N,N-dimethyl-2-butynoate (200) was allowed to react with the (trimethylstannyDcopper reagent (44) under conditions (THF, -48°C-0°C) which cleanly transformed e t h y l 2-butynoate (51) i n t o the b i s ( t r i m e t h y l -stannyl) ester 114, only the protonated amide 205 was obtained a f t e r workup. There was no trace of the (expected) amide 234 on the basis of glc (column A) analysis. A small amount (<10% by glc) of the bis(trimethylstannyl) amide 234 was produced when HMPA was added and the reaction mixture was s t i r r e d at room temperature for 12 h (equation 53). But, much more important to the above discussion, the remainder of the product mixture was the protonated (E) amide 205, with no trace of the isomeric (Z) amide 208 (glc analysis, column A). Thus i t appears that, for the conditions under which the amides 224 were prepared (THF-HMPA, -78°C - room temperature), the intermediate formed i s c o n f i g u r a t i o n a l l y stable, and therefore the amides 224 l i k e l y possess the (E) configuration. It should also be noted that the (phenylthio)-cuprate 14, which was not as e f f e c t i v e as the reagents 44_ and 45_ i n forming bis(trimethylstannyl) esters, under the same reaction conditions gave a 1:1 mixture (glc analysis) of the bis(trimethylstannyl) amide 234 and the (E) amide 205 (equation 54). It might also be noted that, as yet, the stereochemical configu-r a t i o n of the bis(trimethylstannyl) amide 234 has not been rigorously determined and i s represented as (E) only by analogy with the bis(trimethylstannyl) esters 115. - 90 -Me,Sn^ ^ONMej Me,Sn + Me-C=C-CONMe 2 • \ — / THF—HMPA / \ 2 0 0 -78°C — rt M e S n M e » M e CONMe, le c 2 3 4 2 0 5 Me aSnCu>SMe t 1 9 (53) [Me,SnCuSPh]Li 1:1 ( 5 4 > Me 3Sn C0 2R' R / ^SnMe, 115 I t i s not obvious why the i n te rmed ia te s de r i ved from the a d d i t i o n of ( t r i r a e th y l s t anny l ) c up r a t e s to amides 197 are amenable to t r app ing w i t h carbon e l e c t r o p h i l e s wh i l e the corresponding e s t e r i n te rmed ia te s 79^  and 80_ are. no t . S u p e r f i c i a l l y , t h i s d i f f e r e n c e may be r a t i o n a l i z e d on the bas i s of a decreased tendency of the amide i n te rmed ia te s to couple w i t h excess reagent (hence forming b i s ( t r i m e t h y l s t a n n y l ) compounds i n a s i m i l a r manner to that o ccu r r i n g when the e s te r i n te rmed ia te s were warmed above -48°C) , and thereby a l l o w i n g the temperature to be r a i s e d s u f f i c i e n t l y f o r a l k y l a t i o n to occur . U n f o r t u n a t e l y , t h i s i s an exp l ana t i on of an obse rva t i on u s ing an obse rva t i on without an e x p l a n a t i o n . There must be some unde r l y i ng reason(s) f o r both these - 91 -occurrences. Presumably, the reasons are related to the nature of the intermediate 223 and should explain not only the above mentioned differences i n r e a c t i v i t y but also account for the differences i n configurational s t a b i l i t y between the intermediate 223 and the corresponding intermediate i n the ester s e r i e s . One may speculate that the p r i n c i p a l reason for a l l these differences i s related to the r e l a t i v e tendencies of the intermediates 79 and 223 to isomerize into the a l l e n i c structures 82_ and 235, r e s p e c t i v e l y (Scheme 19). As mentioned previously (see section IIIA), the amide intermediate 223, due to resonance s t a b i l i z a t i o n , should be less l i k e l y to isomerize into an a l l e n i c enolate such as 235. This explains why the amide intermediate 223 appears to be c o n f i g u r a t i o n a l l y more stable than the ester intermediate 79. If one postulates that the intermediate 223 may be trapped with carbon e l e c t r o p h i l e s because i t i s a vinylcopper-type species while the ester vinylcopper-type intermediate 79 isomerizes to the a l l e n i c enolate 82_ (which does not re a d i l y react with carbon e l e c t r o p h i l e s ) at temperatures high enough for reaction with carbon e l e c t r o p h i l e s to occur, then one may r a t i o n a l i z e why compounds such as 224 could be r e a d i l y prepared while the corresponding esters 35_ could not. F i n a l l y , i f one postulates that a,6-bis(trimethylstannyl) compounds (such as 115 and 233) are formed from a l l e n i c intermediates such as 82_ and 235 but not from vinylcopper-type intermediates such as 79 and 223, then one may explain the observation that the b i s ( t r i m e t h y l -stannyl) esters 115 are more r e a d i l y formed than the corresponding amides 233. - 92 -Me,Sn H R CO,R' 3 5 Me 3Sn Cu-Li 79 Me,Sn R OR1 82 OCu-Li Me,Sn CONMe, Me,Sn CO.R' *>=< R H R SnMe, R SnMe, 2 3 3 115 Me,Sn Z OCu-Li R NMe, 2 3 5 z Me,Sn Cu-Li w R CONMe, 2 2 3 Me,Sn v H R CONMe, 2 2 4 Scheme 19 When we attempted to trap the intermediate 236 with iodine (THF, -78°C), we obtained none of the desired iodo amide 237 but only recovered the s t a r t i n g butynamide 200 (equation 55). This observation indicates that, as with a,8-acetylenic esters, the reaction of a,B-acetylenic amides 197 with (trimethylstannyl)copper reagents i s re v e r s i b l e . - 93 -Me-C5C-C0NMe 2 + Me,SnCu-SMet 2 0 0 4 4 Me,Sn Cu X Me CONMe, 2 3 6 Me,Sn I M x ( 5 5 ) Me CONMe, 237 D. Reactions of B-trlmethylstannyl-a,B-unsaturated- N,N-dlmethylanides Regardless of the reasons for the differences which we have observed between reactions of the esters 20_ and amides 197 with (trimethylstannyDcopper reagents, we could now prepare compounds of general structure 224. In theory, d i r e c t transmetalation of 224, or transmetalation a f t e r appropriate functional group manipulation, would afford highly substituted v i n y l l i t h i u m reagents 238 or 37_ (Scheme 20). We have b r i e f l y Investigated some of these p o s s i b i l i t i e s . To test the f e a s i b i l i t y of d i r e c t l y transmetalating B-trimethyl-stannyl-a,8-unsaturated-N,N-diraethylamides we chose to study the simple amides 205 and 208. Unfortunately, addition of methyllithium to cold - 94 -Scheme 20 (-98°C or -78°C) THF solutions of 205 or 208_ followed by addition of el e c t r o p h i l e s such as iodomethane and cyclohexanone did not produce s y n t h e t i c a l l y useful y i e l d s of trapped products. Instead, mixtures of uni d e n t i f i e d products, presumably a r i s i n g from various transmetalation, deprotonation, and Michael addition processes, were obtained. For example, i n a reaction employing amide 205 as the substrate and cyclohexanone as the e l e c t r o p h i l e there was obtained small amounts of compounds ten t a t i v e l y i d e n t i f i e d as 240 and 241. T y p i c a l l y , the *H nmr spectrum of the crude product showed no resonances due to trimethyl-stannyl groups but showed many signals around 6 3 i n d i c a t i n g a mixture of dimethylamides. Analysis of the products by t i c also indicated - 95 -mixtures of products. This approach was eventually discontinued. 2 4 0 241 Attempts at transforming the amides 205 and 208 into other d e r i v a t i v e s also met with only limited success. For example, treatment of the amide 205 with a variety of reducing agents ( l i t h i u m aluminum hydride i n ether, lithium diethoxyaluminum hydride i n ether, d i i s o b u t y l -alurainum hydride in ether, 9-BBN in THF, and lithium triethylborohydride i n THF) gave complex mixtures of products, including the isomeric amide 208. The amide 208 was the only product observed when the amide 205 was treated with hot d i l u t e base (3 M NaOH i n Et0H-H 20) (equation 56) while the saturated amide 242 was the only product observed on treatment of the amide 205 with diisobutylaluminum hydride i n dimethoxyethane (equation 57). Eventually, i t was found that the amide 205 could be converted 6 2 into the known ester 29_ by treatment with Meerwein's s a l t followed by hydrolysis of the intermediate with aqueous sodium bicarbonate (equation 58). Since previous work in our laboratories had shown that the ester 29 could be transformed into v i n y l l i t h i u m reagents, t h i s provided hope - 96 -Me,Sn NaOH Me,Sn CONMe 2 Me (56) Me CONMe 2 205 2 0 8 DIBAL Me,Sn 2 0 5 (57) DME Me C0NMe 2 2 4 2 that the amides 224 could a l s o be transformed i n t o u s e f u l reagents v i a the corresponding e s t e r s . Un f o r t una te l y , when the more h i g h l y s u b s t i t u -ted amide 232 was t rea ted under the same c o n d i t i o n s , the expected e t h y l e s t e r 243 was not formed (equat ion 59). I n s tead , a smal l amount (11%) of s t a r t i n g m a t e r i a l was recovered w i t h the remainder being h i g h e r -b o i l i n g (po lymer ic ) m a t e r i a l s . Presumably, the d i f f e r e n c e l i e s In the s t e r i c e f f e c t of the methyl group which h inders fo rmat ion of the in te rmed ia te iminium s a l t . S ince N,N-dimethylamides are u s u a l l y good subs t ra te s f o r p a r t i a l r educ t i on to a l d e h y d e s 6 3 , i t seemed that the unsaturated nature of the amides 205 and 208 was re spons i b l e f o r the d i f f i c u l t i e s encountered i n the attempted r educ t i on s . A l s o , a recent report by Kende and T o d e r 6 4 showed that a ,8 -unsaturated e s t e r s cou ld be c l e a n l y deprotonated and a - a l k y l a t e d to produce B,y-unsaturated e s t e r s of p r e d i c t a b l e s t e r e o -chemi s t ry . With these two thoughts i n mind, i t was decided that i f t h i s - 97 -Me,Sn 1> E « ) + B F 4 - Me.Sn ) = \ " ) = \ ( 5 8 ) Me C0NMe 2 2) NaHCO, M e C0 2Et 2 0 5 29 (59) 232 2 4 3 deprotonation-alkylation sequence could be applied to the amides 224, the r e s u l t i n g 8,y -unsaturated amides should be e a s i l y convertible into i n t e r e s t i n g v i n y l l i t h i u m reagents (e.g. equation 60). It was also of i n t e r e s t to determine whether or not the new o l e f i n i c bond would be formed s t e r e o s e l e c t i v e l y and, i f so, with what stereochemistry. Treatment of the amide 232 with lithium 2,2,6,6-tetramethyl-piperidide (LiTMP)-HMPA i n THF at -78°C followed by the addition of iodomethane afforded, a f t e r appropriate workup, a crude product which was e s s e n t i a l l y homogeneous by glc (column B) and t i c analyses. Under the same conditions, LDA-HMPA65 afforded a 4:1 mixture (glc analysis) of the s t a r t i n g amide 232 and the same product, respectively. Eager to e s t a b l i s h the stereochemistry of the expected amide 244 by examination of the Sn-H coupling constant of the y - o l e f i n i c proton, we were somewhat perplexed to find that there was no s i g n a l i n the *H nmr spectrum of the - 98 -product a t t r i b u t a b l e to such a p roton. I n s tead , a t r i p l e t at 5 1.04 (.J = 7.5 Hz) suggested the presence of an e t h y l group. E v e n t u a l l y , t h i s new compound was i d e n t i f i e d as the amide 247 , which presumably a r i s e s v i a 8 ' - r ae t a l a t i on of the amide 232 (equat ion 61) . The 8 ' - m e t a l a t i o n of a,8-unsaturated t e r t i a r y amides has been 6 6 reported very r e c e n t l y by Beak and h i s co-workers . For example, they found that success ive treatment of the amide 248 w i t h sec-buty l l i th ium-TMEDA (THF, -78°C) and 1-iodobutane a f f o rded the amide 249 (equat ion 62). P r i o r to t h e i r work, there had been a number of repor t s of the d ime ta l a t i on of a,8-unsaturated secondary ami d e s 6 7 . I t i s i n t e r e s t i n g to note that LiTMP, a weaker base than s e c - b u t y l l i t h i u m , - 99 -Me Me CONMe, UTMP-HMPA THF 2 3 2 2 4 6 Mel Me,Sn Et CONMe, ( 6 1 ) 2 4 7 i s apparently basic enough to completely metalate the amide 232 while c a LDA, known to be a weaker base than LiTMP , only p a r t i a l l y metalated the amide 232 under the same conditions. 1) S-BuLi-TMEDA 2) n-Bul O I 2 4 8 2 4 9 (62) The result shown i n equation 61 raises many questions. For example, how general i s the reaction - what other substrates and e l e c t r o p h i l e s may be used? If carbonyl compounds can be used as e l e c t r o p h i l e s , can the r e s u l t i n g hydroxy amides be c y c l i z e d into a,3-unsaturated lactones (equation 63)? And can these lactones be - 100 -(63) 2 5 2 f u r t h e r d e r i v a t i z e d into useful v i n y l l i t h i u m reagents? In answering these and other questions, we have thus far only trapped the anion 246 with cyclohexanone to af f o r d the hydroxy amide 253 (equation 64). Cl e a r l y , more work i s required to f u l l y explore the p o t e n t i a l of t h i s i n t e r e s t i n g tangent. - 101 -IV. Addition of (Trimethylstannyl)copper (44) to 1-Alkynes: Synthesis of (^-Substituted 2-Trlmethylstannyl-l-alkenes A. Introduction Work i n our l a b o r a t o r i e s , concurrent w i t h that desc r ibed i n t h i s t h e s i s , had shown that e t h y l (E_ ) -3 - t r imethy l s tanny l -2 -butenoate (29) i s r e a d i l y converted i n t o 4 - c h l o r o - 2 - t r i m e t h y l s t a n n y l - l - b u t e n e (256) wh ich, i n t u r n , may be t ransmeta lated to a f f o r d 4 - c h l o r o - 2 - l i t h i o - l - b u t e n e (257) (Scheme 21) . I t has a l s o been shown that the v i n y l l i t h i u m spec ies 257, and the cuprate reagents 258 and 259 der i ved from i t , are u s e f u l reagents i n va r i ous "one-pot " annu l a t l on p r o c e s s e s 6 9 ' 7 0 . Thus, treatment of e s te r 29_ w i t h LDA fo l l owed by p ro tona t i on of the r e s u l t a n t eno late anion w i t h a c e t i c a c i d at low temperatures a f f o rded a mixture c o n s i s t i n g predominantly (94%) of the 8 , y -un sa tu ra -ted e s te r 254 and a sma l l amount (6%) of the a,8-unsaturated e s t e r 30. These e s t e r s were r e a d i l y separated by column chromatography on s i l i c a g e l . Reduct ion of the e s te r 254, f o l l owed by treatment of the r e s u l t a n t a l c o h o l 255 w i t h P l ^ P - C C l i , 7 1 i n the presence of t r i e t h y l a m i n e a f f o rded the ch lo ro v iny l s tannane 256 (66% y i e l d from 254). T ransmeta la t i on (MeL i , THF, -78°C, 10 min) of 256 prov ided a s o l u t i o n of 4 - c h l o r o - 2 -l i t h i o - l - b u t e n e (257). A d d i t i o n of pheny l th iocopper or cuprous cyanide to the s o l u t i o n of 257, obta ined as desc r ibed above, prov ided s o l u t i o n s of the cuprate reagents 258 and 259 (Scheme 22) . These reagents reacted w i t h a v a r i e t y - 102 -Me,Sn Me C02Et 29 1) LDA 2) HOAc Me,Sn C02Et Me,Sn 0,Et M e ^ ^ 3 0 2 5 4 1) LAH (—255) 2) P h , p - c a 4 CI Me Li Me,Sn. CI 257 2 5 6 Scheme 21 of cyclic enones (260) to provide ketones of general structure 262 which could be cyclized to ketones 263. Alternatively, the ketones 263 could be obtained directly, in a "one-pot" reaction, by cyclization of the intermediate chloro enolate 261. The methylene cyclopentane moiety i s present in a number of terpenoid natural products and the methylene cyclopentane annulation process described above i s potentially very useful in syntheses of such compounds. - 103 -Scheme 22 There are a l s o a number of te rpeno id n a t u r a l products which conta in methylene cyclohexane or methylene cyc loheptane u n i t s . We were - 104 -i n t e r e s t e d i n p repar ing h igher homologs of the ch l o ro v iny l s tannane 256 i n order to determine whether or not the methodology descr ibed above cou ld be extended to the p repa ra t i on of l a r g e r r i n g s . For example, i f a s e r i e s of r eac t i on s analogous to those o u t l i n e d above could be performed s t a r t i n g from the pentenylstannane 264 i n p lace of the butenylstannane 256, t h i s would c o n s t i t u t e a p o t e n t i a l l y u s e f u l methylene cyclohexane annu l a t i on method (equat ion 65) . 2) CuZ 2 6 0 (65) 2 6 4 2 6 5 2 6 6 In view of the well-documented success of the p repa ra t i on of d i -and t r i s u b s t i t u t e d o l e f i n s v i a the a d d i t i o n of a l k y l coppe r reagents to O ft T O "TO 1-alkynes c » » we f e l t that i t might be worthwhi le to i n v e s -t i g a t e the a d d i t i o n of ( t r ime thy l s t anny l ) c oppe r reagents to 1-alkynes as a po s s i b l e route to 2 - t r i m e t h y l s t a n n y l - l - a l k e n e s such as 264. More e x p l i c i t l y , the a d d i t i o n of a l k y l c oppe r reagents der i ved from Gr ignard reagents to t e rm ina l a lkynes i s known to proceed w i t h h igh r e g i o - and s t e r e o s e l e c t i v i t y to produce i n te rmed ia te s of genera l s t r u c t u r e 267. P r o tona t i on of these i n te rmed ia te s a f f o rd s 2 , 2 - d i s u b s t i t u t e d o l e f i n s w h i l e a l k y l a t i o n (w i th R"X) g i ves r i s e to t r i s u b s t i t u t e d o l e f i n s of known s tereochemis t ry (equat ion 66). C l e a r l y , i f ( t r i m e t h y l s t a n n y l ) -- 105 -copper reagents undergo analogous r e a c t i o n s w i t h 1-alkynes (equat ion 67) , t h i s would be a very expedient and v e r s a t i l e route to the compounds of i n t e r e s t . R'Cu-MgX R-CSC-H 4 7 R1 CuMgX x f .R H 267 H R«X R' H H 2 6 8 H R" ,R" X (66) 2 6 9 R-CSC-H 4 7 Me,SnCu-U H X SnMe, R 270 (67) I t should be noted that the hydros tannat ion of 1-alkynes o f t en a f f o r d s mixtures of isomers con ta i n i n g on ly minor amounts of the 2 - t r i m e t h y l s t a n n y l - l - a l k e n e * 1 . For example, r e a c t i o n of 1-hexyne (271) w i t h t r i m e t h y l t i n hydr ide a f f o rded a 2:29:69 mixture of the alkenes 272, 273, and 274, r e s p e c t i v e l y (equat ion 68) . I t should a l so be noted that a l though the a d d i t i o n of ( t r i p h e n y l -s tanny l )copper reagents to acety lene i t s e l f has been r epo r t ed 7 1 * very r e c e n t l y , the a d d i t i o n of ( t r i a l k y l s t a n n y l ) c o p p e r reagents to t e r m i n a l a lkynes has not been repor ted p r i o r to our work. - 106 -O-Bu-CEC-H 271 Me,SnH 60*C Me,Sn SnMe, + + D-Bu D-Bu SnMe, Q-BU 272 2 7 3 274 (68) 229-69 B. Reaction of (trlmethylstannyl)copper (44) with 1-alkynes S ince we were qu i t e i n t e r e s t e d i n p repar ing the pentenylstannane 264, and s ince the p o t e n t i a l p recu r so r , 5 - ch l o r o - l - pen t yne (275), i s commerc ia l ly a v a i l a b l e , we chose to begin our i n v e s t i g a t i o n s i n t h i s area w i t h t h i s a ce t y l ene . When t h i s m a t e r i a l was a l lowed to react w i t h the ( t r ime thy l s t anny l ) c oppe r reagent (44) (THF, -78°C, 6 h ) , app rop r i a te workup a f fo rded an o i l which conta ined , on the bas i s of g l c (column B) a n a l y s i s , hexamethy ld i t i n and a mixture of two products i n a r a t i o of 89:11. Sub jec t i on of t h i s mixture to column chromatography on s i l i c a g e l prov ided a mediocre (58%) y i e l d of the major product . The minor product , f o r reasons s t i l l unknown, was not detected i n the e l u a t e . - 107 -The major product was i d e n t i f i e d as the de s i r ed pentenylstannane 264 on the bas i s of i t s s p e c t r a l p r ope r t i e s (equat ion 69). Thus, the 1 H nmr spectrum conta ined a 9 -proton s i n g l e t at 6 0.16 (w i t h s a t e l l i t e peaks due to Sn-H coup l i n g , J s n - H = 52/54 Hz) d i a g n o s t i c of a t r i m e t h y l s t a n n y l group, a 2-proton m u l t i p l e t around 6 1.9 a t t r i b u t a b l e to the C-4 methylene protons , and two 2-proton t r i p l e t s at 6 2.19 (J_ = 7 Hz) and 3.52 (J = 6.5 Hz) a t t r i b u t a b l e to the C-3 and C-5 methylene protons , r e s p e c t i v e l y . The o l e f i n i c protons gave r i s e to two doublets of t r i p l e t s at 6 5.22 (J = 2.5, 1 Hz) and 5.72 (J = 2.5, 1 Hz ) . The ra the r s imple i r spectrum conta ined a band at 920 cm 1 which i s a s s i gnab le to an o l e f i n i c methylene group and at 770 c m - 1 which i s c h a r a c t e r i s t i c of a t r i m e t h y l s t a n n y l group. In a d d i t i o n , h igh r e s o l u -t i o n mass spectrometry v e r i f i e d that the m a t e r i a l had the molecu lar formula CsHi7ClSn. H-C5C-(CHt),-CI 2 7 5 1) Me,SnCu-SMe2 2) MeOH SnMe, (69) 2 6 4 Al though we were p leased that we cou ld ob ta i n the de s i r ed product 264 i s o m e r i c a l l y pure (an important c on s i de r a t i on s ince i t was a n t i c i p a t e d that 264 would be very d i f f i c u l t to separate from r e g i o -i somers ) , we were r a the r d i sappo in ted w i t h the y i e l d . I t was reasoned that perhaps the low y i e l d was due to incomplete r e a c t i o n and that the - 108 -s t a r t i n g m a t e r i a l was not detected because of i t s v o l a t i l i t y . The p o s s i b i l i t y of a competing deprotonat ion r e a c t i o n , as observed i n the r e a c t i o n s of a l k y l c u p r a t e s w i t h 1-alkynes (equat ion 70) was r u l e d out s ince i t i s known that ( t r ime thy l s t anny l ) c oppe r reagents are protonated on ly s l owly under the cond i t i on s used i n t h i s r e a c t i o n (THF, - 78°C ) , even by a c e t i c a c i d 2 6 ' 1 * 1 * . Deprotonat ion of the 1-alkyne by the v i n y l c oppe r in te rmed ia te was r u l e d out when i t was l a t e r shown that the r e a c t i o n of the ( t r ime thy l s t anny l ) c oppe r reagent (44) w i t h some other a lkynes (e .g . 1 and 54) under the same r e a c t i o n cond i t i on s (THF, -78°C, 6 h) proceeded to complet ion (see below). R-CSC-H + RiCuLi - R-CSC-CuR'U + R"H (70) H-CSC-CH.OTHP H-CSC-CHaOSI-^ 1 5 4 When the a d d i t i o n of kk_ to 275 (equat ion 69) was c a r r i e d out at -78°C or -63°C f o r longer times (18 h ) , no improvement i n y i e l d was observed. However, these experiments d id not r e v e a l much i n f o rma t i on regard ing the cause of the low y i e l d s ob ta ined . I t was decided that more conc lu s i ve r e s u l t s cou ld be obta ined i f a l e s s v o l a t i l e acety lene -one that cou ld be r e a d i l y quan t i t a t ed by g l c - was used as the s t a r t i n g - 109 -material. The acetylene chosen was 8-tetrahydropyranyloxy-l-octyne (277)*. It should be noted that when the above reaction with the acetylene 275 was carried out at -48°C, a small amount of a higher-boiling product was produced. The same product was the major product formed when the chloro acetylene 275 was allowed to react (THF, -78°C) with a solution of the (trimethylstannyl)copper reagent (44) which had been formed using an old sample of CuBr'SMe2. This material was identified as (Z)-l,2-bis(trimethylstannyl)-5-chloro-l-pentene (278). The *H nmr spectrum was similar to that of the mono-trimethylstannyl alkene 264 in the region 6 1 to 4 (methylene proton signals) but clearly showed the presence of two trimethylstannyl groups (9-proton singlets at 6 0.19 and 0.22 with sa t e l l i t e peaks due to Sn-H coupling, £ = 52/54 Hz and 50/52 Hz, respectively) and a single vinyl proton (triplet at 6 6.68, J_ = 1 Hz). As previously noted on a number of occasions, the coupling constant associated with the coupling of the olefinic proton 117 119 with the Sn and Sn nuclei was extremely useful in the determina-tion of stereochemistry. In this case, the observed J values may be interpreted as being due to the presence of one trimethylstannyl group geminal (£sn-H = 82 Hz) to the olefinic proton and another trimethyl-* I am very grateful to Professor L. Weiler and Ms. M.E. Alderdice for a generous gift of l-bromo-6-tetrahydropyranyloxyhexane (276). This material was readily converted into acetylene 277 by reaction with lithium acetylenide-ethylenediamine complex In DMSO. - 110 -s t anny l group t rans (J[sn-H = 188/198 Hz ) * to i t . Thus, i n e f f e c t , the two t r i m e t h y l s t a n n y l groups have been added syn across the t r i p l e bond of the acety lene 275. I t i s l i k e l y that t h i s compound i s formed by i n i t i a l syn a d d i t i o n of the ( t r ime thy l s t anny l ) c oppe r reagent (44) to the acety lene 275 fo l l owed by coup l i ng of the in te rmed ia te 279 w i t h excess 44 (equat ion 71) . Such coup l i n g may be the rma l l y i n i t i a t e d o r c a t a l y z e d by t r a n s i t i o n metal i m p u r i t i e s [such as Cu( I I ) s a l t s formed by a u t o x i d a -t i o n of Cu( I ) s a l t s ] . Me,SnCu*SMe2 H-CECHCH,)!,-CI 275 Cu SnMe, H CI 279 Me,SnCu*SMet Me,Sn SnMe, CI H (71) 278 * A l though other va lues of J s n - H f o r t r a n s v i c i n a l coup l i n g i n 3 - t r i a l k y l s t a n n y l - 2 - a l k e n o a t e s and 3 - t r i a l k y l s t a n n y l - 2 - a l k e n a m i d e have been = 120 Hz, a value of = 180 Hz i s expected f o r an o l e f i n w i thout e l e c t r on -w i t hd raw ing g r o u p s 1 0 c . - I l l -I t i s i n t e r e s t i n g that the only coup l ing product observed i n the above case was the alkene 278 i n which the two t r i m e t h y l s t a n n y l groups are c i s to each o ther , whereas i n our prev ious work w i t h a c e t y l e n i c e s t e r s (20) the only coupled product observed was the ( 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 (115). Th is d i f f e r e n c e i s no doubt r e l a t e d to the a b i l i t y of the in te rmed ia te s 79_ t o i somer ize ( p o s s i b l y to or v i a a l l e n i c eno late type spec ies 82) . In c o n t r a s t , the non-conjugated v i ny l coppe r spec ies 279 has no such route f o r i s o m e r i z a t i o n and the re fo re mainta ins i t s s te reochemica l i n t e g r i t y . Me,Sn Cu-Li R COttV 7 9 Me,Sn M R OR' 82 OCu-Li When the te rm ina l acety lene 277 was a l lowed to react w i t h the ( t r ime thy l s t anny l ) c oppe r reagent (44) (1.5 equ i v . ) i n THF at -78°C f o r 6 h, appropr i a te workup of the r e a c t i o n mixture a f f o rded an o i l which conta ined , on the bas i s of g l c (column B) a n a l y s i s , i n a d d i t i o n to hexamethy l d i t i n , a mixture of s t a r t i n g m a t e r i a l 277, a major product and a minor product i n a r a t i o of 31:65:4, r e s p e c t i v e l y . The compos i t ion of the product mixture was not s i g n i f i c a n t l y d i f f e r e n t ( r a t i o of s t a r t i n g m a t e r i a l and products was 37:61:2) when the r e a c t i o n was a l lowed to proceed f o r much longer times (17 h) wh i l e much more s t a r t i n g m a t e r i a l - 112 -was recovered ( r a t i o of s t a r t i n g acety lene and products was 74:25:1) when the r e a c t i o n was quenched a f t e r only 2 h. When the r e a c t i o n was c a r r i e d out at -63°C f o r 6 h, the r a t i o of s t a r t i n g m a t e r i a l and products obta ined was 29:67:4, r e s p e c t i v e l y . The major product was i d e n t i f i e d as the expected 2 - ( t r i m e t h y l s t a n n y l ) a l k e n e 280. On the bas i s of the above r e s u l t s , we reasoned that (a) the r e a c t i o n of 1-alkynes w i t h the ( t r ime thy l s t anny l ) c oppe r reagent (44) i s qu i t e s low, (b) the reac tant s and the i n te rmed ia te v i n y l coppe r spec ies 281 (equat ion 72) are i n e q u i l i b r i u m and (c) the e q u i l i b r i u m favor s only ma rg i na l l y the in te rmed ia te v i n y l coppe r spec ies 281. The r e v e r s i b i l i t y of the r e a c t i o n (us ing a lkyne 277 as the subs t ra te ) was shown by quench-ing the r e a c t i o n mixture ( a f t e r 6 h at -78°C) w i t h i od i ne (2 equ i v . , -78°C, 3 h) i n s t ead of w i t h a proton source: In t h i s case, the s t a r t i n g m a t e r i a l was recovered i n 94% y i e l d wh i l e none of the product 280 was de tec ted . We have p r e v i ou s l y noted s i m i l a r r e s u l t s i n connect ion w i t h the r eac t i on s of ( t r ime thy l s t anny l ) c oppe r reagents w i t h a , B - a c e t y l e n i c e s t e r s . The r e s u l t s may be exp la ined by pos tu la t ing 1 * 1 * that s t rong e l e c t r o p h i l e s (such as i o d i n e , bromine, or mercu r i c c h l o r i d e ) p u l l the e q u i l i b r i u m to the l e f t by de s t r oy i ng the ( t r i m e t h y l s t a n n y l ) c o p p e r - 113 -reagent f a s t e r than they react w i t h the i n te rmed ia te copper spec i e s . H - C S C - R + Me ,SnCu-SMe, 4 7 4 4 H + H SnMe, K (?2> 2 7 0 I t i s known 1 8 »'*'*» 1 + 7 t ha t ( t r i m e t h y l s t a n n y l ) c o p p e r reagents are very weak bases (pKjjB ra 5 ) and react only s l ow l y , i f at a l l , w i t h weak proton donors such as methanol. On the other hand, v i n y l -copper spec ies formed by the r e a c t i o n of ( t r i m e t h y l s t a n n y l ) c o p p e r reagents w i t h a , 8 - a c e t y l e n i c e s t e r s are r e a d i l y protonated by 18 methanol . There fo re , i n the hope of s h i f t i n g the e q u i l i b r i u m shown i n equat ion 72 to the r i g h t by p ro tona t i on of the i n te rmed ia te 281, we c a r r i e d out the r e a c t i o n of 1-alkynes (47) w i t h the copper reagent 44_ i n the presence of methanol. A f t e r some exper imenta t i on , i t was found that 1-alkynes could be converted e f f i c i e n t l y Into 2 - t r i m e t h y l s t a n n y l - l -a lkenes by treatment of the former substances w i t h 2 iequiv. of reagent 44 (THF, -63°C, 12 h) i n the presence of 60 equ iv . of methanol. Under these c o n d i t i o n s , r e a c t i o n of 1-alkyne 277 proceeded very nea r l y to - 114 -complet ion - g l c a n a l y s i s of the crude product mixture i n d i c a t e d that 4% s t a r t i n g m a t e r i a l remained - and a good (84%) y i e l d of the a d d i t i o n product 280 was i s o l a t e d . Sub jec t i on of other 1-alkynes to the same r e a c t i o n cond i t i on s gave good y i e l d s of a d d i t i o n products (Table X I ) . The use of 120 equ iv . of methanol under the same cond i t i on s (THF, -63°C, 12 h) gave very s i m i l a r r e s u l t s wh i l e the use of " o n l y " 30 equ iv . of methanol r e s u l t e d i n the recovery of more (11%) s t a r t i n g m a t e r i a l . I t may be seen from Table XI that 1-alkynes were converted i n t o 2 - t r i m e t h y l s t a n n y l - l - a l k e n e s i n good y i e l d s i n almost every case. In each case, a lthough a mixture of products was produced, on ly the major product was i s o l a t e d a f t e r column chromatography of the r e a c t i o n mixture (except ent ry 10, see below). The s p e c t r a l data of the i s o l a t e d products f u l l y cor roborated the ass igned s t r u c t u r e s . In gene ra l , the i r spect ra showed the expected bands f o r the f u n c t i o n a l groups present wh i l e the *H nmr spect ra conta ined s i g na l s at the appropr i a te p o s i t i o n s f o r the protons p resent , i n c l u d i n g a p a i r of doublet of t r i p l e t s (J_ - 1 Hz, 2.5 Hz) i n the reg ion 6 5 to 6 s i m i l a r to the s i g n a l s p r e v i o u s l y desc r ibed f o r the o l e f i n i c protons of the pentenylstannane 264. High r e s o l u t i o n mass spec t romet r i c measurements v e r i f i e d the mo lecu la r formulae of the p roduct s . A l though the minor product was not i s o l a t e d i n most cases, i t i s h i g h l y l i k e l y that i t i s the r e g l o chem i ca l l y i somer i c alkene 282. Th i s assignment was made on the ba s i s of the k n o w n 7 2 c h igh s t e r e o s e l e c t -i v i t y (>99.9% syn) observed f o r the a d d i t i o n of organocopper reagents to 1-alkynes and by analogy w i t h the minor products i s o l a t e d i n the cases of e n t r i e s 10 and 11 (Table X I ) . - 115 -Table XI. Addition of (trimethylstannyl)copper (44) to 1-alkynes (47). 4 4 (2 equiv.) R-CHC-H 47 MeOH (60 equiv.) M e j S n H g n M " M + H THF.-63°C. 12h R H R H 270 282 Entry Substrate R[(CH 2) n-X] Products 270:282a Yield (7.)b n X 1 277 6 OTHP 280:289 95: : 5 84 2 60 6 H 290:291 94: : 6 81 3 283 4 OH 292:293 97: 3 85 4 284 4 CI 294:295 92: 8 80 5 198 3 0Si(t-Bu)Me2 296:297 95: 5 82 6 285 3 OH 298:299 98: 2 88 7 275 3 CI 264:300 89: 11 79 8 286 2 0SlU-Bu)Me2 301:302 92: 8 81 9 287 2 OH 255:303 99: 1 82 10 287 2 OH 255:303 91: 9 81 c 11 288 2 CI 256:304 81: 19 59 a Product r a t i o was determined by gl c (column B) analysis of the crude product mixture. Product 282 was not i s o l a t e d except with entries 10 and 11. k Y i e l d of i s o l a t e d , p u r i f i e d 270 a f t e r column chromatography and d i s t i l l a t i o n . The reaction was performed on 0.2 mmol scale. c Reaction was performed on 1.0 mmol scale. Also i s o l a t e d was 8% of the (E_)-l-trimethylstannyl-l-alkene 303. - 116 -In the case of a lkyne 287 (ent ry 10), the minor product was e a s i l y i s o l a t e d by column chromatography of the product mixture and i d e n t i f i e d as ( E ) - 4 - t r i m e t h y l s t a n n y l - 3 - b u t e n - l - o l (303) on the ba s i s of i t s s p e c t r a l da ta . The l r spectrum showed the presence of a t r i m e t h y l -s t anny l group (775 c m - 1 ) and a hydroxy l group (3350 c m - 1 , broad) and suggested the presence of a t rans d i s u b s t i t u t e d carbon-carbon double bond (1600, 990 c m - 1 ) . The l o w - f i e l d (80 MHz) X H nmr spectrum conta ined ( a f t e r a d d i t i o n of D2O) a 9-proton s i n g l e t at 6 0.13 (w i t h s a t e l l i t e peaks due to Sn-H coup l i n g , Jgn-H = 53/55 Hz) c h a r a c t e r i s t i c of a t r i m e t h y l s t a n n y l group, a broad 2-proton t r i p l e t of t r i p l e t s at 6 2.42 (J_ = J_' = 6 Hz) a t t r i b u t a b l e to the a l l y l i c methylene p rotons , a 2-proton t r i p l e t at 6 3.69 (J = 6 Hz) a t t r i b u t a b l e to the C - l methylene protons and a complex 2-proton m u l t i p l e t around 6 6.0. In the h i g h -f i e l d (400 MHz) spectrum, the o l e f i n i c protons gave r i s e to an AB quartet w i t h each l i n e f u r t h e r s p l i t i n t o a t r i p l e t . I r r a d i a t i o n of the s i g n a l at 6 2.42 removed the a d d i t i o n a l coup l i n g and gave a s imple AB qua r te t w i t h J^g = 18.5 Hz. The magnitude of t h i s coup l i ng constant i n d i c a t e d that the o l e f i n i c protons were t rans and, t h e r e f o r e , that the alkene possessed the (E) c o n f i g u r a t i o n . The magnitude of the coup l i ng constants a s s oc i a ted w i t h the coup l i ng of the o l e f i n i c protons w i t h the t i n n u c l e i ( 1 1 7 S n and 1 1 9 S n ) a l so i n d i c a t e d that the c o n f i g u r a t i o n was (E ) : One proton was c i s to the t r i m e t h y l s t a n n y l group (Jj5 n-H = 7 ^ w h i l e the other was geminal ( J s n - H = 82/86 Hz) and the re fo re the two protons must have been t rans to each o the r . - 117 -In the case of a lkyne 288 (ent ry 11), a sma l l amount of the minor product was i s o l a t e d by p repa ra t i ve g l c . I t was i d e n t i f i e d as ( E ) - 4 -c h l o r o - l - t r i m e t h y l s t a n n y l - l - b u t e n e (304) on the ba s i s of i t s s p e c t r a l da ta . The *H nmr spectrum (400 MHz) of t h i s m a t e r i a l was very s i m i l a r to that of the corresponding a l c o h o l 303 ( a f t e r exchange w i t h D 2 0 ) . For the c h l o r i d e 304, J^g = 18.6 Hz and, t h e r e f o r e , i t a l s o possesses the (E) c o n f i g u r a t i o n . I t should a l so be noted that i n the case of a lkyne 288, a r e l a t i v e l y low (59%) y i e l d of the de s i r ed 2 - t r i m e t h y l s t a n n y l - l -a lkene 256 was ob ta ined . In a d d i t i o n , t h i s m a t e r i a l , a f t e r p u r i f i c a -t i o n , was contaminated w i t h a smal l amount (- 2%) of the r e g i o i s o m e r i c product 304. The low y i e l d may be due, i n p a r t , to the amount of the 1 - t r i m e t h y l s t a n n y l - l - a l k e n e 304 formed and to the v o l a t i l i t y of the p roduct . Because of the low y i e l d and the presence of the isomer 304, the ch l o r o butenylstannane 256 i s probably best prepared on a p repa ra -t i v e s c a l e by p repa r ing the a l c o h o l 255 (ent ry 10) and conver t i ng i t i n t o the des i red c h l o r i d e 256. Whi le the r e a c t i o n of the acety lenes shown i n Table XI w i t h the ( t r ime thy l s t anny l ) c oppe r reagent (44) i n THF i n the absence of a proton source d i d not proceed to complet ion , the acety lenes _1 and _54_ reacted e s s e n t i a l l y complete ly a f t e r 6 h at -78°C (equat ions 73, 74). A l s o , u n l i k e the acety lenes shown i n Table X I , these m a t e r i a l s a f f o rded s u b s t a n t i a l (- 30%) amounts of the r e g i o i s ome r i c 1 - t r i m e t h y l s t a n n y l - l -a lkenes 306 and 308. These l a t t e r m a t e r i a l s were r e a d i l y i s o l a t e d by column chromatography of the product mixtures and i d e n t i f i e d as (E) o l e f i n s on the ba s i s of a n a l y s i s of the *H nmr s p e c t r a . - 118 -Me,SnCu-SMe2 SnMe, Me,Sn H - C S C - C H . O R THF,-78°C,6h O R + O R 1 R = T H P 305 70:30 306 (73) 54 R = S H £ 307 72:28 308 (?4> The olefinic protons of a l l of the (E_)-l-trimethylstannyl-l-alkenes we have thus far isolated produced signals in their *H nmr (400 MHz) spectra in a very similar pattern. Typically, these protons gave rise to an AB quartet around 6 6.1 with A6 = 0.15 and J^g = 19 Hz with each line further s p l i t by coupling with the a l l y l i c methylene protons. The downfield doublet was further split into two triplets (J_ = 1 Hz) by a l l y l i c coupling while the upfield doublet was further split into triplets (J_ = 6 Hz) by vicinal coupling. Interpretation of this region of the high-field 1H nmr spectra unequivocally ascertained the stereochemical assignments. We have previously noted that the chromatographic behaviour of the isomeric products obtained from the addition of (trimethylstannyl)-copper reagents to a,8-acetylenic esters and amides may be reliably correlated with the stereochemistry of the products. With the products from the addition of the copper reagent 44_ to 1-alkynes, the major product was Invariably eluted before the corresponding minor product on - 119 -g l c (column B) a n a l y s i s . In the cases i n which the minor product was i s o l a t e d , i t was shown to be the corresponding ( l E ) - l - t r i m e t h y l s t a n n y l -1-alkene. Hence the chromatographic behaviour of the other minor products i s f u r t h e r i n d i r e c t evidence of t h e i r s t r u c t u r e s . The i s o l a t e d ( E ) - l - t r i m e t h y l s t a n n y l - l - a l k e n e s were a l s o c o n s i s t e n t l y more po l a r by t i c a n a l y s i s than the corresponding 2 - t r i m e t h y l s t a n n y l - l - a l k e n e s . I t i s not obvious why the r e a c t i o n of the a lkynes 1 and J54_ w i t h the copper reagent 44^ proceeds e s s e n t i a l l y to complet ion i n the absence of methanol i n con t ra s t w i t h the behaviour of the other a lkynes i n v e s t i g a t e d . Perhaps, w i t h the e l ec t r on -w i thd raw ing X group on ly one carbon away from the u n s a t u r a t i o n , the i n te rmed ia te v i n y l coppe r spec ies 309 and 310 are r e l a t i v e l y more s t a b l e . The observed decreased r e g i o -s e l e c t i v i t y may be due to b e t t e r s t a b i l i z a t i o n of the i n te rmed ia te 310 Me,Sn Cu 311 Me,Sn Cu OR 310 - 120 -when the e l ec t ron -w i thd raw ing group X i s c l o se to the an i on i c cen te r . In other words, a l though the c lo se p rox im i t y of X s t a b i l i z e s the i n te rmed ia te 309 compared to other i n te rmed ia te s 281, i t s t a b i l i z e s i n te rmed ia te s 310 r e l a t i v e l y more compared to other i n te rmed ia te s 311. Thus, one may r a t i o n a l i z e why the a lkynes _1. a n a " J>4. r e a c t w i t h the copper reagent 44_ f u r t h e r , and w i t h decreased r e g i o s e l e c t i v i t y , than the other 1-alkynes i n v e s t i g a t e d . A c o n t r i b u t i n g f a c t o r to the decreased r e g i o s e l e c t i v i t y observed may be the i n i t i a l fo rmat ion of a complex such as 312 which d i r e c t s the copper atom to the 2 - p o s i t i o n . The complex 313 has p r e v i o u s l y been invoked to e x p l a i n the r e g i o s e l e c t i v i t y observed i n the a d d i t i o n of n -buty lcopper to 3-ethoxypropyne (314) (equat ion 75) a . Br Me»Sn^Q u^Li, X H-CSC-CHj 312 313 n-BuCu-MgBr 2 D-Bu Bu? H-CSC-CHjOEt ether + 314 315 316 (75) 97 3 With the alkynes possess ing a two-carbon or longer s i d e - c h a i n , - ( C H 2 ) n - X , the r e g i o s e l e c t i v i t y seemed to depend on both the l eng th of - 121 -the s i d e - c h a i n and the f u n c t i o n a l group X. For example, w i t h X = CI the percentage of the corresponding minor isomer was 19, 11, and 8 f o r n = 2,3, and 4, r e s p e c t i v e l y (Table X I , e n t r i e s 4 ,7 ,10) . S i m i l a r i n c r e a s i n g r e g i o s e l e c t i v i t y w i t h i n c r e a s i n g cha in l eng th was observed f o r the other f u n c t i o n a l groups i n v e s t i g a t e d . Th i s may be due to a decreased tendency to form complexes such as 312 as the chain l eng th inc reases and the s i z e of the ( p o t e n t i a l ) che l a te r i n g i n c r ea se s . I t appears that even when such coo rd i na t i on i s u n l i k e l y (Table X I , e n t r i e s 1,2), the r a t i o of isomers formed i s - 95:5. I t may w e l l be that the isomer r a t i o s observed are a r e f l e c t i o n of the r e l a t i v e s t a b i l i t i e s of the i n te rmed ia te s 281 and 311. In summary, we have been able to prepare e f f i c i e n t l y a number of w - s u b s t i t u t e d - 2 - t r i m e t h y l s t a n n y l - l - a l k e n e s (270) by the r e g i o s e l e c t i v e a d d i t i o n of ( t r ime thy l s t anny l ) c oppe r (44) to 1-a lkynes. Some of these p roduct s , such as the pentenylstannane 264 and the hexenylstannane 294 may be u s e f u l i n " one-pot " methylene cyclohexane and methylene cyc loheptane processes , r e s p e c t i v e l y , and these p o s s i b i l i t i e s are c u r r e n t l y being i n v e s t i g a t e d i n our l a b o r a t o r i e s . - 122 -EXPERIMENTAL I. General Melting points were taken on a Fischer-Johns melting point apparatus and are uncorrected. Boiling points are also uncorrected and those indicated as air-bath temperatures refer to short path (Kugelrohr) d i s t i l l a t i o n s . Infrared ( i r ) spectra were obtained on liquid films or chloroform solutions, employing Perkin-Elmer models 710 or 710B spectro-photometers and were calibrated using the 1601 cm-1 band of polystyrene film. Proton nuclear magnetic resonance (*H nmr) spectra were taken in deuterochloroform solution using Varian Associates models T-60, EM-360, HA-100 or XL-100 spectrometers or Bruker models WP-80 or WH-400 spectro-meters. Signal positions are given in 6 units, with tetramethylsilane (TMS) as the internal standard. In cases of compounds with trimethyl-stannyl and/or t r i a l k y l s i l y l groups the resonance positions were determined relative to the chloroform signal (7.25 a ) . The multipli-city, number of protons, coupling constants (where possible) and assign-ments are indicated in parentheses. The tin-proton coupling constants (J_ S n_ H) are given as £i i 7 S n _ H / J _ i i 9 S n _ H where the coupling constants for the two isotopes are distinct and as an average of the two values where they are not distinct. For compounds exhibiting ABX type spectral, the quoted values of J^x a n d £BX a r e measured from the appropriate line splittings, although these values only approximate the actual coupling constants 7 5k. Low resolution mass spectra were - 123 -recorded w i t h a Varian/MAT CH4B mass spectrometer wh i l e h igh r e s o l u t i o n mass spec t ra were recorded w i t h a Kratos/AEI MS 50 or MS 902 mass spectrometer. In cases of compounds w i t h t r i a l k y l s t a n n y l groups the molecular weight determinat ions (h igh r e s o l u t i o n mass spectrometry) were based on 1 2 0 S n and were u s u a l l y made on the ( M + - a l k y l ) p e a k 7 6 . M i c r o -analyses were performed by Mr. P. Borda, M i c r o a n a l y t i c a l Labo ra to ry , U n i v e r s i t y of B r i t i s h Columbia. A n a l y t i c a l g a s - l l q u i d chromatography ( g l c ) was performed on a Hewlet t -Packard model 5832A gas chromatograph us ing a 6 f t x 0.125 i n . s t a i n l e s s s t e e l column packed w i t h 3-5% OV-17 on 80-100 mesh Chromosorb W(HP) (column A) and a thermal c o n d u c t i v i t y d e t e c t o r , or on a Hew le t t -Packard model 5880 gas chromatograph us ing a 25 m x 0.21 mm fused s i l i c a column coated w i t h c r o s s - l i n k e d SE-54 (column B) and a flame i o n i z a t i o n d e t e c t o r . P r epa ra t i v e g l c was done on a Va r i an Aerograph model 90-P instrument equipped w i t h a 10 f t x 0.25 i n . s t a i n l e s s s t e e l column packed w i t h 10% 0V-17 on 60-80 mesh Chromosorb W(HP) and a thermal c o n d u c t i v i t y de t e c t o r . T h i n - l a y e r chromatography ( t i c ) was c a r r i e d out on commercial p l a s t i c - b a c k e d s i l i c a g e l p l a t e s (Eastman Chromagram Sheet Type 13181) or on aluminum-backed p l a t e s (E. Merck, Type 5554). P r epa ra t i v e t i c was accomplished on 20 x 20 cm g las s p l a t e s coated w i t h 0.7 mm of s i l i c a g e l (E. Merck, S i l i c a ge l 60). Convent iona l column chromatography was done on 70-230 mesh s i l i c a g e l (E. Merck, S i l i c a Ge l 60) w h i l e f l a s h 77 chromatography was done on 230-400 mesh s i l i c a g e l (E. Merck, S i l i c a Ge l 60 ) . - 124 -Unless otherwise s t a t e d , a l l r e a c t i on s were c a r r i e d out under an atmosphere of dry argon us ing e i t h e r oven or c a r e f u l l y f l ame -d r i ed g lassware. Cold temperatures were mainta ined by use of the f o l l o w i n g b a t h s 7 8 : aqueous ca lc ium c h l o r i d e / C 0 2 ? 9 ( -20°C) , acetonitr i le/CC>2 (-48°C), ch loroform/C0 2 ( -63°C), acetone/C0 2 (-78°C) and methanol/N 2 ( -98°C). A l i s t of General Procedures may be found a f t e r the L i s t of Tab le s . A l l compounds which were c h a r a c t e r i z e d by h igh r e s o l u t i o n mass measurements were homogeneous by g l c and t i c ana ly se s . II. Solvents and Reagents So lvents and reagents were p u r i f i e d and d r i e d us ing e s t a b l i s h e d 8 0 81 procedures » d r y i n g agents used are summarized i n Table X I I . A l l s o l ven t s were d i s t i l l e d before use. The petroleum ether used was the f r a c t i o n w i t h a b o i l i n g range ca . 30-60°C. Hexamethy ld i t i n and h e x a - n - h u t y l d i t i n were obta ined from the A l f a D i v i s i o n of the Ventron Corporat ion or from Organometa l l i c s , I nc . S o l u t i on s of m e t h y l l i t h l u m - l i t h i u m bromide complex i n ether and n - b u t y l l i t h i u m i n hexane were obta ined from A l d r i c h Chemical Co., I nc . 8 2 and were s tandard i zed us ing the d o u b l e - t l t r a t i o n procedure of Gilman D i i sobuty la luminum hydr ide (DIBAL) as a 1.0 M s o l u t i o n i n hexane was a l s o obta ined from A l d r i c h . Pheny l th iocopper was prepared us ing a m o d i f i c a t i o n of the method - 125 -Table X I I . P u r i f i c a t i o n of so l ven t s and reagents . M a t e r i a l Dry ing Agent Reference A c e t o n i t r i l e P2O5 81a Dichloromethane P 2 0 5 80 D i i sopropy lamine CaH 2 ' 81e Dimethoxyethane Na/Ph 2CO 81a N,N-Dimethy1formamide a CaH 2 81c Dimethyl s u l f o x i d e 3 CaH 2 81c E thano l Mg(OEt) 2 81g E t h y l ch loroformate K 2 C 0 3 80 E t h y l e ther Na/Ph 2CO 81a Hexamethylphosphoramide* 5 CaH 2 81c Hexane CaH 2 80 Methanol Mg(OMe) 2 81g Methy l ch loroformate K 2 C 0 3 80 P y r i d i n e CaH 2 81e Te t r ahyd ro f u r an Na/Ph 2CO 81a T r i e thy l am ine CaH 2 81e a D i s t i l l e d under reduced pressure (20 T o r r ) . k D i s t i l l e d under reduced pressure (0.3 T o r r ) . - 126 -of Posner . Thus a mixture of cuprous ox ide (46 g, 0.32 mol) and th iopheno l (79 g, 0.72 mol) In abso lute e thano l (1400 mL) was heated under r e f l u x f o r seven days. The r e s u l t a n t ye l l ow s l u r r y was s u c t i o n f i l t e r e d , and the c o l l e c t e d s o l i d was washed thoroughly w i t h e thano l and e t h e r , and then d r i e d f o r s e ve r a l days under h igh vacuum. Copper bromide-dimethyl s u l f i d e complex was prepared by the method of House a , a f t e r washing commercial cuprous bromide w i t h m e t h a n o l 2 5 b . ( 3 -Methoxy -3 -methy l - l -butyny l ) copper was prepared by the method 0 ft of A tk in son a from cuprous c h l o r i d e and 3 -methoxy -3 -methy l - l -b u t y n e 2 8 b . Cuprous cyanide was purchased from J .T . Baker Co. and used 2 9b without f u r t h e r p u r i f i c a t i o n L i t h i u m d i i sop ropy lamide (LDA) was prepared by the a d d i t i o n of a s o l u t i o n of i i - b u t y l l i t h i u m i n hexane to a s o l u t i o n of d i i s op ropy lamine (1.1 equ i v . ) i n anhydrous t e t r ahyd ro fu ran at -78°C. The r e s u l t i n g c o l o r l e s s or s l i g h t l y ye l l ow s o l u t i o n was then s t i r r e d at 0°C f o r 10 min 8 3 before be ing used . Saturated ba s i c aqueous ammonium c h l o r i d e (pH 8) was prepared by the a d d i t i o n of * 50 mL of aqueous ammonium hydroxide (58%) to 1 L of sa tu ra ted aqueous ammonium c h l o r i d e . - 127 -III. Preparation of (Trialkylstannyl)copper Reagents 23 Preparation of Trimethylstannyllithium To a cold (-20°C), s t i r r e d s o l u t i o n of hexamethylditin i n anhydrous tetrahydrofuran (- 10 raL per mmol of hexamethylditin) was added a solu t i o n of methyllithium i n ether (1.0 equiv.). The r e s u l t i n g yellow solution was s t i r r e d at -20°C for 15 min to afford a solution of trimethylstannyllithium. Preparation of Tri - n - b u t y l s t a n n y l l i t h i u m To a cold (0°C), s t i r r e d s o l u t i o n of hexa-n-butylditin i n anhydrous tetrahydrofuran (= 10 mL per mmol of hexa-n-butylditin) was added a solu t i o n of n-butyllithium i n hexane (1.0 equiv.). The re s u l t i n g yellow solution was s t i r r e d at 0°C for 15 min to afford a solut i o n of tri-n_-butylstannyllithium. Preparation of Lithium (Phenylthio)(trimethylstannyl)cuprate (14) [Me3SnCuSPh]Li To a cold (-20°C), s t i r r e d solution of trimethylstannyllithium (0.39 mmol, prepared as outlined above) i n 5 mL of anhydrous tetrahydro-furan was added i n one portion s o l i d phenylthiocopper (67.3 mg, 0.39 mmol). The r e s u l t i n g yellow s l u r r y was s t i r r e d at -20°C for 15 min to af f o r d a dark red solution of lithium (phenylthio)(trimethylstannyl)-cuprate (14). - 128 -P repa r a t i on of L i t h i um B i s ( t r i m e t h y l s t a n n y l ) c u p r a t e (43) [Me3SnCuSnMe,]Li To a co l d ( -48°C), s t i r r e d s o l u t i o n of t r i m e t h y l s t a n n y l l i t h i u m (0.78 mmol, prepared as o u t l i n e d above) i n 5 mL of anhydrous t e t r ahyd ro fu ran was added i n one p o r t i o n s o l i d cuprous bromide-d imethyl s u l f i d e (80.1 mg, 0.39 mmol). The r e s u l t i n g s l u r r y was s t i r r e d at -48°C f o r 15 min to a f f o r d a dark red s o l u t i o n of the cuprate 43_ (0.39 mmol). P r e p a r a t i o n of the (T r imethy l s tanny l ) copper Reagent (44) Me3SnCu>SMe2 To a co l d ( -78°C), s t i r r e d s o l u t i o n of t r i m e t h y l s t a n n y l l i t h i u m (0.39 mmol, prepared as o u t l i n e d above) i n 5 mL of anhydrous t e t r a h y d r o -f u r an was added i n one p o r t i o n s o l i d cuprous bromide-d imethy l s u l f i d e (80.1 mg, 0.39 mmol). The r e s u l t i n g s l u r r y was s t i r r e d at -63°C f o r 15 min to a f f o r d a dark red s o l u t i o n of kh_ (0.39 mmol). - 129 -P repa ra t i on of L i t h i u m ( 3 -Me thoxy - 3 -methy l - l - bu t yny l ) -( t r i m e t h y l s t a n n y l ) c u p r a t e (45) [Me3SnCuCEC -CMe20Me] Li To a co ld ( -48°C), s t i r r e d s o l u t i o n of t r i m e t h y l s t a n n y l l i t h i u m (0.39 mmol, prepared as o u t l i n e d above) i n 5 mL of anhydrous t e t r a h y d r o -furan was added i n one p o r t i o n s o l i d ( 3 -methoxy - 3 -methy l - l - bu t yny l ) -copper (62.7 mg, 0.39 mmol). The r e s u l t i n g s l u r r y was s t i r r e d at -48°C f o r 15 min to a f f o r d a dark red s o l u t i o n of the cuprate reagent 45_ (0.39 mmol). P r e p a r a t i o n of L i t h i um (Cyano ) ( t r imethy l s t anny l ) cup ra te (46) [Me,SnCuCN]Li To a co l d ( -78°C), s t i r r e d s o l u t i o n of t r i m e t h y l s t a n n y l l i t h i u m (0.39 mmol, prepared as o u t l i n e d above) i n 5 mL of anhydrous t e t r ahyd ro fu r an was added i n one p o r t i o n s o l i d cuprous cyanide (34.9 mg, 0.39 mmol). The r e s u l t i n g mixture was s t i r r e d at -78°C f o r 5 min then at -48°C f o r 15 min to a f f o r d a b r i g h t orange s o l u t i o n of the cyano-cuprate 46 (0.39 mmol). - 130 -P r epa r a t i on of L i t h i um ( P h e n y l t h i o ) ( t r i - n - b u t y l s t a n n y l ) c u p r a t e (181) [n-Bu,SnCuSPh]Li To a co ld ( -20°C), s t i r r e d s o l u t i o n of t r i - n - b u t y l s t a n n y l l i t h i u m (12.0 mmol, prepared as o u t l i n e d above) i n 100 mL of anhydrous t e t r ahyd ro fu r an was added i n one p o r t i o n s o l i d pheny l th iocopper (2.06 g, 12.0 mmol). The r e s u l t i n g ye l l ow s l u r r y was s t i r r e d at -20°C f o r 15 rain to a f f o r d a dark red s o l u t i o n of the cuprate reagent 181 (12.0 mmol). P r epa r a t i on of the ( T r i - n - b u t y l s t a n n y l ) c o p p e r Reagent (182) n-Bu3SnCu*SMe2 To a co ld ( -78°C), s t i r r e d s o l u t i o n of t r i - r i - b u t y l s t a n n y l l i t h i u m (3.80 mmol, prepared as o u t l i n e d above) i n 20 mL of anhydrous t e t r a -hydrofuran was added i n one p o r t i o n s o l i d cuprous bromide-d imethyl s u l f i d e (780 mg, 3.80 mmol). The r e s u l t i n g s l u r r y was s t i r r e d at -78°C f o r 30 min to a f f o r d a dark red s o l u t i o n of the copper reagent 182 (3.80 mmol). - 131 -IV. Reaction of (Trimethylstannyl)copper Reagents with  g,p>-Acetylenlc Esters A. Preparation of g,B-Acetylenlc Esters Genera l Procedure A: P r epa r a t i on of g , B -Ace t y l en i c E s t e r s R-C5C-C0 2R' To a co ld ( -78°C), s t i r r e d s o l u t i o n of the approp r i a te t e r m i n a l a lkyne (47) i n anhydrous te t rahyd ro fu ran was added a s o l u t i o n of me thy l -l i t h i u m i n e the r . The r e s u l t i n g c o l o r l e s s s o l u t i o n was s t i r r e d at -78°C f o r 10 min, was warmed to -20°C and s t i r r e d at t h i s temperature f o r 1 h. E t h y l or methyl ch loroformate was added and the r e s u l t i n g ye l l ow s o l u t i o n was s t i r r e d at -20°C f o r 1 h, warmed to room temperature and s t i r r e d f o r a f u r t h e r 1 h. Saturated aqueous sodium b icarbonate and ether were added. The organ ic l a y e r was separated, washed w i t h s a t u r a -ted aqueous sodium b i ca rbonate , and d r i ed over anhydrous magnesium s u l f a t e . So lvent removal ( r o t a r y evaporat ion) f o l l owed by d i s t i l l a t i o n of the r e s i d u a l o i l a f f o rded the correspond ing a , 8 - a c e t y l e n i c e s t e r (20 ) . P r epa r a t i on of E t h y l 2-Butynoate ( 5 1 ) 8 4 Me-C5C-C0 2Et - 132 -Fo l l ow ing genera l procedure A o u t l i n e d above, a s o l u t i o n of propyne (= 1.2 g, 30 mmol) i n 50 mL of dry t e t rahyd ro fu ran was t r e a t e d s u c c e s s i v e l y w i t h a s o l u t i o n of m e t h y l l i t h i u m i n ether (20.7 mL, 25 mmol) and e t h y l ch loroformate (2.87 mL, 30 mmol). Normal workup, f o l l owed by f r a c t i o n a l d i s t i l l a t i o n of the crude m a t e r i a l through a 15 cm V ig reux column, a f fo rded 2.44 g (87%) of e t h y l 2-butynoate (51) as a c o l o r l e s s l i q u i d (bp 62-64°C/12 To r r ; l i t . 8 4 bp 163-164°C). Th i s m a t e r i a l e x h i b i t e d i r ( f i l m ) : 2230, 1710, 1260 c m - 1 ; *H nmr (80 MHz, C D C 1 3 ) 6: 1.31 ( t , 3H, - O C H 2 C H 3 , J - 7 Hz ) , 2.02 ( s , 3H, a l k y n y l methy l ) , 4.27 ( q , 2H, -OCH 2 CH 3 , J = 7 Hz ) . p C P repa ra t i on of E t h y l 2-Pentynoate (53) E t - C S C - C O t E t To a co ld ( -78°C), s t i r r e d s o l u t i o n of 1-butyne (= 3.0 g, 56 mmol) i n 100 mL of anhydrous t e t r ahyd ro fu ran was added a s o l u t i o n of m e t h y l l i t h i u m i n ether (47 mL, 50 mmol). The r e s u l t i n g c l e a r , c o l o r l e s s s o l u t i o n was s t i r r e d at -78°C f o r 10 min, warmed to -20°C and s t i r r e d at t h i s temperature f o r 1 h. E t h y l ch loroformate (6.21 mL, 65 mmol) was added and the ye l l ow s o l u t i o n was s t i r r e d at -20°C f o r 1 h and at room temperature f o r 1 h. Normal workup, as o u t l i n e d i n genera l procedure A, f o l l owed by f r a c t i o n a l d i s t i l l a t i o n of the crude m a t e r i a l through a 15 cm V ig reux column, a f fo rded 5.65 g (90%) of pure e t h y l 2-pentynoate (53) - 133 -(bp 68°C/12 To r r ; l i t . 8 5 bp 67-68°C/18 T o r r ) . Th i s m a t e r i a l e x h i b i t e d i r ( f i l m ) : 2255, 1708 c m - 1 ; XH nmr (80 MHz, CDCI3) 6: 1.21 ( t , 3H, CCH 2 CH 3 , J = 7.5 Hz ) , 1.31 ( t , 3H, -0CH 2 CH 3 , J = 7.0 Hz ) , 2.37 (q , 2H, CCH 2 CH 3 , J = 7.5 Hz ) , 4.24 (q , 2H, -OCH 2 CH 3 , J = 7.0 Hz ) . 3 2 P repa ra t i on of 3 - ^ t - B u t y l d i m e t h y l s i l o x y ) - l - p r o p y n e (54) -V-SiOCH2-CSC-H ' I 86 Fo l l ow ing the procedure of Corey and Venkateswarlu , a mix ture of 2 - p r o p y n - l - o l (1.12 g, 20 mmol), t - b u t y l d i m e t h y l c h l o r o s l l a n e (3.62 g, 24 mmol), and im idazo le (3.40 g, 50 mmol) i n 40 mL of anhydrous N,N-dimethylformamide was s t i r r e d f o r 12 h at room temperature. Saturated aqueous sodium b icarbonate and ether were added. The organ ic l a y e r was separated, washed thoroughly w i t h sa tu ra ted aqueous sodium b i ca rbona te , and d r i ed over anhydrous magnesium s u l f a t e . The so l vent was removed ( r o t a r y evaporat ion) and the r e s u l t i n g y e l l ow o i l was d i s t i l l e d (bp 48°C/15 To r r ; l i t . 3 2 b bp 37-39°C/4.0 Tor r ) to a f f o r d 3.26 g (96%) of the t e rm ina l acety lene 54_ as a c l e a r , c o l o r l e s s l i q u i d . Th i s m a t e r i a l e x h i b i t e d i r ( f i l m ) : 3300, 2100, 1260, 1100, 840 c m - 1 ; *H nmr (80 MHz, CDC1 3) 6: 0.15 ( s , 6H, M e 2 S i - ) , 0.94 ( s , 9H, M e 3 C S i - ) , 2.40 ( t , IH, C=CH, J = 2 Hz ) , 4.31 ( d , 2H, - 0 C H 2 - , J = 2 Hz ) . Exact Mass c a l c d . f o r C 9 H 1 8 0 S i : 170.1126; found: 170.1117. - 134 -P repa r a t i on of E t h y l 4 - ( t - B u t y l d i m e t h y l s i l o x y ) - 2 - b u t y n o a t e (55) ^-SiOCHrCSC-COaEt Fo l l ow ing genera l procedure A o u t l i n e d above, a s o l u t i o n of 3 - ( t j - b u t y l d i m e t h y l s i l o x y ) - l - p r o p y n e (54) (1.70 g, 10 mmol) i n 30 mL of anhydrous te t rahyd ro fu ran was t r e a t ed s u c ce s s i v e l y w i t h m e t h y l l i t h i u m (9.32 mL, 11 mmol) and e t h y l ch loroformate (1.15 mL, 12 mmol). Normal workup f o l l owed by b u l b - t o - b u l b d i s t i l l a t i o n of the r e s i d u a l o i l under reduced pressure ( a i r - b a t h temperature 78-85°C/0.1 To r r ) a f fo rded 2.03 g (83%) of the a , B - a c e t y l e n i c e s t e r _5_5_ as a c l e a r , c o l o r l e s s o i l . Th i s m a t e r i a l e x h i b i t e d i r ( f i l m ) : 2220, 1710, 1250, 1110, 1060, 840 c m - 1 ; 1 H nmr (80 MHz, CDC1 3) 6: 0.14 ( s , 6H, Me2S i - ) , 0.92 ( s , 9H, M e j C S i - ) , 1.30 ( t , 3H, -OCH2CH3, J - 7 Hz ) , 4.24 ( q , 2H, -OCH2CH3, J = 7 Hz ) , 4.43 ( s , 2H, -CCH 2 0 - ) . Exact Mass c a l c d . f o r C 1 2 H 2 2 0 3 S i : 242.1338; found: 242.1291. 2 6 P repa ra t i on of l -B romo-2 - (2 -cyc lopenteny l )e thane (63) To a co l d ( 0°C ) , s t i r r e d s l u r r y of t r ipheny lphosph ine (8.66 g, 33 mmol) i n 75 mL of anhydrous a c e t o n i t r i l e was added 1.69 mL (33 mmol) of - 135 -bromine. The r e s u l t i n g wh i te suspension of t r i pheny l pho sph i ne -87 dibromide was s t i r r e d at 0°C f o r 15 min. T r i e thy l am ine (8.36 mL, 60 mmol) and a s o l u t i o n of 2 - ( 2 - c y c l o p e n t e n y l ) e t h a n o l * (3.36 g, 30 mmol) i n 5 mL of a c e t o n i t r i l e were then added and the r e a c t i o n mixture was s t i r r e d at room temperature f o r 30 min. The mix tu re was d i l u t e d w i t h 300 mL of petroleum ether and f i l t e r e d through a short column of s i l i c a g e l . The column was e l u t ed w i t h a f u r t h e r 200 mL of petroleum e the r . Concent ra t i on (atmospheric pressure d i s t i l l a t i o n ) of the combined e l ua te s f o l l owed by d i s t i l l a t i o n ( a i r - b a t h temperature 65-70°C/12 To r r ; l i t . 2 6 bp 95-100°C/35 To r r ) of the r e s i d u a l o i l gave 4.61 g (88%) of the bromide 63_ as a c l e a r , c o l o r l e s s o i l . Th i s m a t e r i a l e x h i b i t e d i r ( f i l m ) : 3030, 720 c m - 1 ; *H nmr (60 MHz, CDCI3) 6: 1.06-1.66 (m, IH), 1.66-2.50 (m, 5H), 2.50-3.00 (m, IH, t e r t i a r y p r o t on ) , 3.29 ( t , 2H, -CH^Br, J = 7 Hz ) , 5.47-5.83 (m, 2H, o l e f i n i c p r o t on s ) . P r epa r a t i on of 4 - ( 2 -Cyc l open teny l ) - l - bu t yne (56) CH2-C=C-H To a coo l (10°C), s t i r r e d s l u r r y of l i t h i u m a c e t y l i d e - e t h y l e n e -diamine complex (2.18 g, 23.6 mmol) i n 10 mL of anhydrous d imethy l * Th i s a l c o h o l may be prepared by the l i t h i u m aluminum hydr ide r e d u c t i o n of ( 2 - c y c l o p e n t e n y l ) a c e t i c a c i d . - 136 -sulfoxide was added dropwise the bromide j63_ (3.44 g, 19.7 mmol) over a period of 15 mi n 3 3 . After the addition was complete, the reaction mixture was allowed to warm to room temperature and s t i r r e d for a further 2 h. Hydrochloric acid (6 M, 10 mL) was added slowly and the r e s u l t i n g mixture was extracted thoroughly with ether (4 x 25 mL). The combined extracts were washed with water (2 x 10 mL), dried over anhydrous magnesium s u l f a t e , and concentrated (rotary evaporation). D i s t i l l a t i o n (air-bath temperature 58-61°C/12 Torr) of the re s i d u a l o i l gave 1.69 g (71%) of the terminal alkyne 56_ as a clear , c o l o r l e s s l i q u i d . This material exhibited i r ( f i l m ) : 3295, 3035, 2100, 730, 640 cm - 1; XH nmr (80 MHz, CDC1 3) 6: 1.1.2-1.75 (m, 3H), 1.94 ( t , IH, -C=C-H, J_ = 1.4 Hz), 2.05-2.50 (m, 5H), 2.55-3.00 (m, IH, t e r t i a r y proton), 5.55-5.83 (m, 2H, o l e f i n i c protons). Exact Mass calcd. for C9H12: 120.0939; found: 120.0934. Preparation of Methyl 5-(2-Cyclopentenyl)-2-pentynoate (57) Following the general procedure A outlined above, a solution of the terminal alkyne J 3 6 ( 1 . 6 8 g, 1 4 . 0 mmol) i n 5 0 mL of anhydrous tetrahydrofuran was treated sequentially with a solution of methyl-l i t h i u m i n ether ( 1 2 . 4 mL, 1 5 . 4 mmol) and, aft e r the reaction mixture - 137 -had been s t i r r e d at -78°C for 1 h and at -20°C for 1 h, with methyl chloroformate (1.30 mL, 16.8 mmol). D i s t i l l a t i o n ( a i r - b a t h temperature 82-85°C/0.2 Torr) of the r e s i d u a l o i l a f t e r workup afforded 2.04 g (82%) of the a,8-acetylenic ester 5_7_ as a cl e a r , c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 3030, 2210, 1710, 1260 cm"1; XH nmr (100 MHz, CDC1 3) 6: 1.18-1.76 (m, 3H), 1.88-2.46 (m, 5H), 2.56-2.94 (m, IH, t e r t i a r y proton), 3.74 (s, 3H, -0CH 3), 5.54-5.83 (m, 2H, o l e f i n i c protons). Exact Mass calcd. for C n H n ^ : 178.0994; found: 178.0981. 8 9 Preparation of (3-Cyclohexenyl)methanol (64) To a w e l l - s t i r r e d s l u r r y of lithium aluminum hydride (0.91 g, 24 mmol) i n 150 mL of anhydrous ether was added dropwise methyl 3-cyclo-hexenecarboxylate (5.60 g, 40 mmol) at such a rate as to maintain gentle r e f l u x . After the addition was complete, the sl u r r y was s t i r r e d for an ad d i t i o n a l period of 1 h. Sodium sulfate decahydrate was added slowly u n t i l hydrogen evolution ceased. The r e s u l t i n g white s l u r r y was treated with anhydrous magnesium su l f a t e and f i l t e r e d through a short column of F l o r i s i l . The column was washed with 300 mL of ether and the eluates were combined. D i s t i l l a t i o n ( air-bath temperature 78-85°C/12 Torr; l i t . 8 9 bp 99-100°C/25 Torr) of the re s i d u a l o i l obtained a f t e r removal - 138 -(rotary evaporation) of the solvent gave 3.87 g (87%) of the desired alcohol 64_ as a clear , c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 3350 (broad), 3030, 1650 cm - 1; *H nmr (80 MHz, C D C 1 3 ) 6: 1.0-2.3 (m, 7H), 3.53 (d, 2H, -CH2OH, J = 5 Hz), 5.65-5.75 (ra, 2H, o l e f i n i c protons). Exact Mass calcd. for C 7H 1 20: 112.0888; found: 112.0897. 9 0 Preparation of 4-(Bromomethyl)cyclohexene (65) To a cold (0°C), s t i r r e d suspension of triphenylphosphine (1.44 g, 5.5 mmol) i n 10 mL of anhydrous a c e t o n i t r i l e was added 0.27 mL (5.4 mmol) of bromine. The r e s u l t i n g white suspension of triphenylphosphine-dibromide 8 7 was s t i r r e d at 0°C for 15 min. Triethylamine (1.40 mL, 10 mmol) was added, followed by a solution of the alcohol 64_ (560 mg, 5.0 mmol) i n 2 mL of anhydrous a c e t o n i t r i l e . The reaction mixture was s t i r r e d at room temperature for 1 h, di l u t e d with 50 mL of petroleum ether and f i l t e r e d through a short column of s i l i c a g e l . The column was washed with another 100 mL of petroleum ether. D i s t i l l a t i o n ( air-bath temperature 72-78°C/12 Torr; l i t . 9 0 bp 79.5-85.5°C/12 Torr) of the o i l obtained on removal (atmospheric pressure d i s t i l l a t i o n ) of the solvent from the combined eluates afforded 687 mg (79%) of the bromide 65_ as a - 139 -c l e a r , c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 3020, 1640, 1420 cm - 1; *H nmr (80 MHz, CDC1 3) 6: 1.0-1.6 (m, 2H), 1.6-2.4 (m, 5H), 3.37 (d, 2H, -CH 2Br, J = 6 Hz), 5.52-5.85 (m, 2H, o l e f i n i c protons). Exact Mass calcd. for C 7 H n 7 9 B r : 174.0044; found: 174.0044. Preparation of 3-(3-Cyclohexenyl)propyne (58) aCH2-C=C-H To a cool (10°C), s t i r r e d suspension of lithium a c e t y l i d e -ethylenediamine complex (1.66 g, 18 mmol) in 10 mL of anhydrous dimethyl sulfoxide (DMSO) was added slowly a solution of the bromide 65 3 3 (2.62 g, 15 mmol) in 5 mL of dry DMSO . Aft e r the addition was complete (15 min) the reaction mixture was s t i r r e d at room temperature for 2 h. Hydrochloric acid (6 M, 10 mL) was added slowly, the r e s u l t i n g quenched reaction mixture was dilu t e d with water (10 mL) and thoroughly extracted with ether (4 x 50 mL). The combined organic extracts were washed with water (2 x 15 mL) and dried over anhydrous magnesium s u l f a t e . D i s t i l l a t i o n (air-bath temperature 62-68°C/12 Torr) of the l i q u i d obtained on removal (atmospheric pressure d i s t i l l a t i o n ) of the solvent afforded 978 mg (54%) of the terminal alkyne _58_ as a c l e a r , c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 3280, 3000, 2100 cm - 1; *H nmr (100 MHz, C D C I 3 ) 6: 1.1-1.6 (m, 3H), 1.6-2.3 (m, 6H), 1.97 - 140 -( t , IH, -C=C-H, J = 1.4 Hz), 5.6-5.7 (m, 2H, o l e f i n i c protons). Exact  Mass calcd. for C9H12: 120.0939; found: 120.0942. Preparation of Methyl 4-(3-Cyclohexenyl)-2-butynoate (59) Following the general procedure A outlined above, a solution of the acetylene 5_8_ (978 mg, 8.15 mmol) i n 50 mL of anhydrous tetrahydro-furan was allowed to react with methyllithium (1.24 M in ether, 7.88 mL, 9.78 mmol) and the r e s u l t i n g acetylide was acylated with methyl chloroformate (0.82 mL, 10.6 mmol). D i s t i l l a t i o n (air-bath temperature 85-92°C/0.4 Torr) of the yellow o i l obtained a f t e r workup of the reaction mixture afforded a clea r , c o l o r l e s s o i l which was >97% pure by g l c (column A) an a l y s i s . Subjection of t h i s o i l to column chromato-graphy (30 g s i l i c a gel, e l u t i o n with petroleum ether-ether, 40:1) gave, a f t e r concentration and d i s t i l l a t i o n of the appropriate f r a c t i o n s , 1.12 g (77%) of a clear , c o l o r l e s s o i l which was homogeneous by t i c and glc (column A) analyses. This material showed i r ( f i l m ) : 3000, 2220, 1710, 1260 cm - 1; *H nmr (80 MHz, CDCI3) 6: 1.2-2.3 (ra, 7H), 2.37 (broad d, 2H, -CH2CHC-, J = 6 Hz), 3.78 (s, 3H, -0CH 3), 5.6-5.7 (m, 2H, o l e f i n i c protons). Exact Mass calcd. for C u H 1 1 + 0 2 : 178.0994; found: 178.0988. - 141 -Preparation of Methyl 2-Nonynoate (61) n-C6H13-C=C-C02Me To a cold (-78°C), s t i r r e d s o l u t i o n of 1-octyne (1.10 g, 10 mmol) in 40 mL of anhydrous THF was added a solution (10.3 mL, 11 mmol) of methyllithium i n ether. The reaction mixture was s t i r r e d at -78°C for 1 h and at -20°C for 1 h. Methyl chloroformate (1.00 mL, 13 mmol) was added and the r e s u l t i n g yellowish solution was s t i r r e d at -20°C for 1 h and at room temperature for 1 h. Normal extractive workup employing ether (100 mL) and saturated aqueous sodium bicarbonate (3 x 15 mL), as described i n general procedure A, afforded, a f t e r d i s t i l l a t i o n (air-bath temperature 70-75°C/0.2 Torr; l i t . 9 1 bp 85°C/2.3 Torr) of the res i d u a l o i l , 1.49 g (88%) of a c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 2220, 1710, 1260, 1080 cm"1; XH nmr (80 MHz, CDC1 3) 6: 0.7-1.0 (m, 3H, -CH 2CH 3), 1.1-1.8 (m, 8H), 2.31 (broad t, 2H, -CEC-CH2-, J_ = 6 Hz), 3.73 (*s, 3H, -0CH 3). Preparation of 1,l-Dibromo(cyclopropyl)ethylene (67) To a reagent prepared by s t i r r i n g together zinc dust (6.54 g, - 142 -100 mmol), triphenylphosphine (26.2 g, 100 mmol) and carbon tetrabroraide (33.2 g, 100 mmol) i n 120 mL of anhydrous dichloromethane at room temperature for 27 h was added 3.50 g (50 mmol) of cyclopropanecarbox-34 aldehyde . The r e s u l t i n g tan s l u r r y was s t i r r e d at room temperature for 2 h. Petroleum ether (500 mL) was added and the supernatant solution was decanted from the r e s u l t i n g red o i l . The o i l was dissolved i n dichloromethane (100 mL). Petroleum ether (500 mL) was added to the resultant solution and the supernatant solution was decanted from the r e s u l t i n g granular p r e c i p i t a t e . The above d i s s o l u t i o n - p r e c i p i t a t i o n procedure was repeated twice more. The combined supernatants were concentrated (rotary evaporation) and the r e s u l t i n g o i l was f l a s h d i s t i l l e d (0.05 Torr, receiving bulb cooled to -78°C) to y i e l d 7.51 g (67%) of the dibromo o l e f i n 67_ as a cl e a r , c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 3060, 2990, 960, 785, 770 cm"1; XH nmr (100 MHz, CDC1 3) 6: 0.4-0.6 and 0.7-0.9 (m, m, 2H each, cyclopropyl methylene protons), 1.4-1.8 (m, IH, cyclopropyl methine proton), 5.81 (d, IH, C=CH, J = 9 Hz). Exact Mass calcd. for C 5 H 6 8 1 B r 2 : 227.8796; found: 227.8804. Preparation of Methyl Cyclopropylpropynoate (68) c - P r - C 5 C - C 0 2 M e To a cold (-78°C), s t i r r e d solution of the dibromo o l e f i n 67 - 143 -(4.52 g, 20 mmol) i n 120 mL of anhydrous tetrahydrofuran was added a solution of methyllithium i n ether (33.9 mL, 42 mmol). The r e s u l t i n g c o l o r l e s s solution was s t i r r e d at -78°C for 1 h, allowed to warm to room temperature and s t i r r e d for a further 1 h. It was then cooled to -20°C and methyl chloroformate (1.70 mL, 22 mmol) was added. The r e s u l t i n g yellow solution was s t i r r e d at -20°C for 1 h, allowed to warm to room temperature and s t i r r e d for a further 1 h. Saturated aqueous sodium bicarbonate and ether were added. The organic layer was washed with saturated aqueous sodium bicarbonate, dried over anhydrous magnesium sulfate and concentrated to afford a brown o i l . D i s t i l l a t i o n ( a i r - b a t h temperature 80-85°C/20 Torr) of the res i d u a l o i l gave 1.92 g (78%) of methyl cyclopropylpropynoate (68), homogeneous by t i c and glc (column A) analyses, as a clear , c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 2990, 2940, 2210, 1700, 1270 cm"1; *H nmr (80 MHz, CDC1 3) 6: 0.85-0.95 (m, 4H, cyclopropyl methylene protons), 1.2-1.5 (m, IH, cyclopropyl raethine proton), 3.72 (s, 3H, -OCH3). Exact Mass calcd. for C7H8O2: 124.0525; found: 124.0525. 9 2 Preparation of 1,l-Dibromo-3-methyl-l-butene (70) To a reagent prepared by s t i r r i n g together zinc dust (10.5 g, 160 mmol), triphenylphosphine (42.0 g, 160 mmol), and carbon t e t r a -- 144 -bromide (53.1 g, 160 mmol) i n 200 mL of dichloromethane at room tempera-ture for 24 h was added 2-methylpropanal. The r e s u l t i n g tan suspension was s t i r r e d at room temperature for 2 h. Petroleum ether (1000 mL) was added and the supernatant solution was decanted from the o i l . The o i l was taken up i n 200 mL of dichloromethane. Petroleum ether (1000 mL) was added and the supernatant solution was decanted from the r e s u l t i n g red o i l . Concentration (rotary evaporation) of the combined super-natants, followed by f l a s h d i s t i l l a t i o n (0.1 Torr, receiving bulb cooled to -78°C) of the residual o i l afforded 10.6 g (58%) of the dibromo o l e f i n 70_ as a clear , c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 1600, 1460, 1160, 870, 790 cm"1; % nmr (80 MHz, CDC1 3) 6 : 0.99 (d, 6H, -CHMe2, J = 7 Hz), 2.55 (d of septets, IH, -CHMe2, J = 7, 9 Hz), 6.21 (d, IH, =CH, J_ = 9 Hz). Preparation of Methyl 4-Methyl-2-pentynoate (71) i - P r - C £ C - C 0 2 M e To a cold (-78°C), s t i r r e d s o l u t i o n of the dibromo o l e f i n 70_ (9.12 g, 40 mmol) in 200 mL of anhydrous tetrahydrofuran was added a so l u t i o n (68 mL, 84 mmol) of methyllithium i n ether. After the re s u l t i n g yellow solution had been s t i r r e d at -78°C for 1 h, and at room temperature for 1 h, i t was cooled to -20°C. Methyl chloroformate (3.71 - 145 -mL, 48 mmol) was slowly added and the reaction mixture was s t i r r e d 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 washed with saturated aqueous sodium bicarbonate, dried over anhydrous magnesium su l f a t e and concentrated (rotary evaporation). D i s t i l l a t i o n (bp 58°C/13 Torr) of the residual o i l yielded 2.64 g (52%) of the a, 8-acetylenic ester 7_1_ as a clear , c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 2210, 1710, 1385, 1370, 1260 cm - 1; *H nmr (80 MHz, CDC1 3) 6: 1.18 (d, 6H, Me2CH-, J = 7 Hz), 2.64 (septet, IH, Me2CH-, J = 7 Hz), 3.72 (s, 3H, -0CH 3). Exact Mass calcd. for C 7 H 1 0 0 2 : 126.0681; found: 126.0685. B. Reaction of Ethyl 2-Butynoate with (Trimethylstannyl)- copper Reagents General Procedure B: Reaction of Ethyl 2-Butynoate (51) with the (Trimethylstannyl)copper Reagents 43-46 To a cold (-78°C), s t i r r e d solution of the appropriate (trimethylstannyl)copper reagent (0.39 mmol) i n 5 raL of anhydrous tetrahydrofuran (THF) was added ethyl 2-butynoate (51) (33.6 mg, 0.3 mmol) as a solution i n 0.5 mL of anhydrous THF. The reaction mixture was s t i r r e d at -78°C or -48°C for 3 h. Saturated basic (pH 8) aqueous ammonium chloride (- 5 mL) and ether (- 30 mL) were added and the re s u l t i n g mixture was allowed to warm to room temperature with vigorous s t i r r i n g . Vigorous s t i r r i n g was maintained u n t i l the aqueous phase - 146 -became deep blue. The organic layer was separated, washed with saturated pH 8 aqueous ammonium chlo r i d e , and dried over anhydrous magnesium s u l f a t e . The solvent was removed and the crude r e s i d u a l o i l was p u r i f i e d by short-path d i s t i l l a t i o n . a) With (trimethylstannyl)copper (44) Following the general procedure B outlined above, ethyl 2-butynoate (33.7 rag, 0.3 mraol) was allowed to react with (tr i r a e t h y l -stannyDcopper (44) i n 5.5 mL of anhydrous THF at -78°C for 3 h. Glc (column A) analysis of the c o l o r l e s s o i l obtained a f t e r workup showed the presence of only hexamethylditin and a single product. Hexamethyl-d i t i n was removed by d i s t i l l a t i o n ( air-bath temperature <70°C/12 Torr) and the residue was d i s t i l l e d (air-bath temperature 85-92°C/12 Torr) to afford 63.2 mg (76%) of a cl e a r , c o l o r l e s s o i l . This material was i d e n t i f i e d as ethyl (E_)-3-trimethylstannyl-2-butenoate (29) by compari-son of i t s chromatographic and spectral properties with those of an authentic sample of the ester 29_ previously prepared i n our labora-18 26 to r i e s ' . In p a r t i c u l a r , t h i s material exhibited i r ( f i l m ) : 1712, 1603, 1180, 770 cm - 1; h nmr (80 MHz, CDC1 3) 6: 0 . 2 0 (s, 9H, -SnMe3, iSn-H = 5 2 / 5 4 H z ) > l ' 2 9 (t» 3 H » - 0 C H 2 C H 3 , J = 7 Hz), 2.39 (d, 3H, v i n y l methyl, J = 2 Hz, Js n-H = 5 0 H z ) » 4 - 1 8 («L. 2 H> - O C H 2 C H 3 , J = 7 CO aEt Me 2 9 3 0 - 147 -Hz), 5.99 (q, IH, v i n y l proton, J = 2 Hz, J s n _ H = 7 2 Hz)« Reaction of ethyl 2-butynoate (33.6 mg, 0.3 mmol) with (trimethylstannyl)copper (44) (0.39 mmol) i n 5.5 mL of anhydrous THF at -48°C (rather than -78°C) for 3 h followed by normal workup afforded 56.5 mg (68%) of e s s e n t i a l l y pure ethyl (E_)-3-trimethylstannyl-2-butenoate. Glc analysis (column A.) of th i s material showed that <1% of the (Z) isomer was present. b) With l i t h i u m (3-methoxy-3-methyl-l-butynyl) (trimethylstannyl)cuprate (45) Following the general procedure B outlined above, et h y l 2-butynoate (33.7 mg, 0.3 mmol) was allowed to react with the cuprate 45_ (0.39 mmol) i n 5.5 mL of anhydrous tetrahydrofuran at -48°C for 4 h. D i s t i l l a t i o n (air-bath temperature 90-95°C/12 Torr) of the o i l obtained a f t e r workup afforded 68.3 mg (82%) of a cl e a r , c o l o r l e s s o i l . Glc analysis (column A) of th i s o i l showed that It consisted of only one (>99%) component with a retention time i d e n t i c a l with that of the ester 29. Hi nmr spectroscopy confirmed t h i s material to be ethyl (E)-3-trimethylstannyl-2-butenoate (29). c) With lithium bis(trimethylstannyl)cuprate (43) Following the general procedure B outlined above, et h y l - 148 -2-butynoate (33.5 mg, 0.3 mmol) was allowed to react with lithium b i s -(trimethylstannyl)cuprate (43) (0.39 mmol) in 5.5 mL of anhydrous THF at -48°C for 4 h. Normal workup followed by d i s t i l l a t i o n (air-bath temperature = 95°C/12 Torr) of the r e s u l t i n g o i l afforded 61.3 mg (74%) of a clear , c o l o r l e s s o i l . Glc analysis (column A) of th i s o i l showed that i t consisted of a 32:68 mixture of two components. These components were separated by preparative t i c on s i l i c a gel using petroleum ether-ether, 100:1 as developing solvent. The minor component (lower band) was i d e n t i f i e d by i t s chromatographic (glc and t i c ) and spectral (^ H nmr) properties as the (E) butenoate 29. S i m i l a r l y , the major component was i d e n t i f i e d as ethyl (Z)-3-trimethylstannyl-2-butenoate 30_ 1 8» 2 6. In p a r t i c u l a r , this material exhibited XH nmr (80 MHz, CDC1 3) 6: 0.18 (s, 9H, -SnMe3, isn-H = 5 3 / 5 6 H z ) > l ' 2 8 3 H » -OCH2CH3, J = 7 Hz), 2.13 (d, 3H, v i n y l methyl, J = 2 Hz, J s n _ H = 45 Hz), 4.18 (q, 2H, -OCHjCHg, J = 7 Hz), 6.40 (q, IH, v i n y l proton, J = 2 H z > iSn-H = 1 1 6 H z ) * d) With lithium (cyano)(triraethylstannyl)cuprate (46) Following the general procedure B outlined above, e t h y l 2-butynoate (33.6 mg, 0.3 mmol) was allowed to react with the (cyano)-cuprate 46_ (0.39 mmol) in 5.5 mL of anhydrous THF at -48°C for 2 h. Normal workup followed by d i s t i l l a t o n (air-bath temperature 85-94°C/12 Torr) of the crude o i l afforded 71.4 mg (86%) of a c l e a r , c o l o r l e s s o i l . Glc analysis (column A) and *H nmr spectroscopy indicated that the - 149 -mixture consisted of a 96:4 mixture (glc r a t i o ) of the (_E) butenoate 29_ and the (Z) butenoate 30, res p e c t i v e l y . C. Preparation of Alkyl (E)- and (Z)-3-Trinettaylstannyl-2-alkenoates General Procedure C: Preparation of A l k y l (E)-3-Trimethylstannyl-2-alkenoates (21). Reaction of (Trimethylstannyl)copper with g,B-Acetylenic Esters Me3Sn C02R' To a cold (-78°C), s t i r r e d s o l u t i o n of the (trimethylstannyD-copper reagent (44) (0.39 mmol) in 5 mL of anhydrous tetrahydrofuran was added the appropriate a,B-acetylenic ester (20) (0.3 mmol) as a solu t i o n i n - 0.5 mL of anhydrous THF. The dark red solution was s t i r r e d at -78°C for 3 h. Saturated aqueous basic ammonium chloride (= 0.5 mL) and ether (30 mL) were added and the r e s u l t i n g mixture was allowed to warm to room temperature with vigorous s t i r r i n g . S t i r r i n g was maintained for a few minutes u n t i l the aqueous layer became deep blue and the organic layer was clear. The organic layer was separated, washed with saturated aqueous basic ammonium chloride ( 2 x 5 mL), dried over anhydrous - 150 -magnesium s u l f a t e , and concentrated under reduced pressure. The resi d u a l o i l was chromatographed on 3 g of s i l i c a g e l . E l u t i o n of the column with petroleum ether (= 10 mL) gave hexamethylditin. Subsequent el u t i o n of the column with ether ( = 10 mL), followed by concentration (rotary evaporation) of the appropriate f r a c t i o n s and d i s t i l l a t i o n (Kugelrohr) of the combined crude product gave the corresponding a l k y l (E_)-3-trimethylstannyl-2-alkenoate (21). General Procedure D: Preparation of A l k y l (Z)-3-Trimethylstannyl-2-alkenoates. Reaction of Lithium (Phenylthio)(trimethylstannyl)cuprate  with a,B-Acetylenic Esters under "Thermodynamic Conditions" Me3Sn C02R' y To a cold (~78°C), s t i r r e d s o l u t i o n of lithium (phenylthio)-(trimethylstannyl)cuprate (14) (0.39 mmol) i n 5 mL of anhydrous tetrahydrofuran was added the appropriate a,B-acetylenic ester (20) (0.3 mmol) as a solution i n = 0.5 mL of anhydrous THF. The reaction mixture was s t i r r e d at -78°C for 15 min, warmed to -48°C and s t i r r e d at that temperature for 4 h. Methanol or ethanol (= 0.2 mL) and ether (30 mL) were added and the mixture was allowed to warm to room temperature. The r e s u l t i n g f l o c c u l e n t yellow s l u r r y was treated with anhydrous magnesium sulf a t e and then was f i l t e r e d through a short column of F l o r i s i l . The - 151 -column was eluted with a further 30 mL of ether and the combined eluate was concentrated under reduced pressure. Subjection of the crude o i l thus obtained to chromatography on s i l i c a g el (8 g, petroleum ether-ether mixture as eluant) , followed by concentration of the appropriate f r a c t i o n s , and d i s t i l l a t i o n (Kugelrohr) of the crude product afforded the corresponding a l k y l (Z)-3-triraethylstannyl~2-alkenoate (22). Preparation of Methyl (E_)-4-Methyl-3-trimethylstannyl-2-butenoate (91) Me 3Sn Me Following general procedure C outlined above, methyl 4-methyl-2-pentynoate (71) (38.0 mg, 0.3 mmol) was converted into the ester 9j_ (67.6 mg, 77%, air-bath d i s t i l l a t i o n temperature 108-115°C/12 T o r r ) . This material was e s s e n t i a l l y pure by glc (column A) and t i c ( e l u t i n g solvent: petroleum ether-ether, 100:1; R f = 0.36) analyses and exhibited i r ( f i l m ) : 1710, 1580, 1180, 780 cm - 1; *H nmr (80 MHz, CDCI3) 6: 0.20 (s, 9H, -SnMe3, J s n _ H = 52/54 Hz), 1.02 (d, 6H, -CHMe2, J = 7 Hz), 3.68 (s, 3H, -0CH 3), 4.02 (d of septets, IH, -CHMe2, J = 7, 1 Hz), 5.87 (d, IH, o l e f i n i c proton, J = 1 Hz, Jgn-H = 7 6 Hz) • Exact Mass calcd. f or C 9H 1 70 2Sn (M+-CH3): 277.0251; found: 277.0253. - 152 -Preparation of Methyl (Z)-4-Methyl-3-trimethylstannyl-2-butenoate (92) Following general procedure D outlined above, methyl 4-methyl-2-butynoate (38.1 mg, 0.3 mmol) was converted into a mixture of methyl (E)- and (Z)-4-methyl-3-triraethylstannyl-2-butenoate, (91) and (92), i n a r a t i o of 6:94 (glc a n a l y s i s ) , r e s p e c t i v e l y . Subjection of t h i s mixture to column chromatography on s i l i c a gel (8 g, e l u t i o n with petroleum ether-ether, 100:1) provided a c o l o r l e s s l i q u i d (Rf = 0.46) which upon d i s t i l l a t i o n (air-bath temperature 105-115°C/12 Torr) gave 64.1 mg (73%) of pure (Z) butenoate 92_. This material exhibited i r ( f i l m ) : 1700, 1590, 1310, 1210, 780 cm - 1; lE nmr (80 MHz, CDClj) 6: 0.14 (s, 9H, -SnMe3, i s n _ H = 52/55 Hz), 1.03 (d, 6H, -CHMe2, J = 7 Hz), 2.72 (d of septets, IH, -CHMe2, £ = 7 , 1 Hz), 3.71 (s, 3H, -0CH 3), 6.36 (d, IH, o l e f i n i c proton, J = 1 Hz, Js n_H = 1 2 6 H z ^ ' Exact Mass calcd. for C 9H 1 70 2Sn (M +-CH 3): 277.0251; found: 277.0254. Preparation of Methyl (E_)-3-Cyclopropyl-3-(trimethylstannyl)-propenoate (93) Me3Sn ,C0 2Me Me,Sn - 153 -Following general procedure C outlined above, methyl cyclopropyl-propynoate (37.0 mg, 0.3 mmol) was converted into 70.2 mg (81%) of a c o l o r l e s s o i l (air-bath d i s t i l l a t i o n temperature 85-92°C/12 T o r r ) . This material was e s s e n t i a l l y (>98%) homogeneous by glc (column A) a n a l y s i s , consisted of a single spot by t i c (R f = 0.21; petroleum ether-ether, 100:1) a n a l y s i s , and exhibited i r ( f i l m ) : 3060, 1710, 1570, 1200, 1180, 1150, 780 cm - 1; XH nmr (80 MHz, CDC13) 6: 0.18 (s, 9H, -SnMe3, Jgn-H = 53/55 Hz), 0.4-0.7 and 0.8-1.1 (m, m, 2H each, cyclopropyl methylene protons), 3.1-3.4 (m, IH, cyclopropyl methine proton), 3.72 (s, 3H, -OCH3), 5.95 (d, IH, o l e f i n i c proton, J = 1 Hz, Js n-H = 7 1 H z ) * E x a c t  Mass calcd. for C 9H 1 50 2Sn (M +-CH 3): 275.0094; found: 275.0083. Preparation of Methyl (Z)-3-Cyclopropyl-3-(trimethylstannyl)-propenoate (94) Following general procedure D outlined above, methyl cyclopropyl-propynoate (37.0 mg, 0.3 mmol) was converted into a mixture of methyl (E)- and (Z^-3-cyclopropyl-3-(trimethylstannyl)propenoate, (93) and (94), in a r a t i o of 5:95 (glc a n a l y s i s ) , r e s p e c t i v e l y . Subjection of t h i s mixture to column chromatography on s i l i c a gel (8 g, e l u t i o n with petroleum ether-ether, 100:1) provided an o i l (Rf = 0.45) which upon - 154 -d i s t i l l a t i o n (air-bath temperature 92-100°C/12 Torr) afforded 62.2 mg (72%) of methyl (Z)-3-cyclopropyl-3-(trimethylstannyl)propenoate (94) as a c o l o r l e s s l i q u i d . This material exhibited i r ( f i l m ) : 3070, 1700, 1320, 780 cm - 1; lW nmr (80 MHz, CDC 13) 6: 0.19 (s, 9H, -SnMe3, Jgn-H = 54/56 Hz), 0.5-1.0 (m, 4H, cyclopropyl methylene protons), 1.6-1.9 (m, IH, cyclopropyl methine proton), J_ = 1 Hz, Js n_H = 1 1 8 H z ) « Exact  Mass calcd. for C 9H 1 50 2Sn (M +-CH 3): 275.0094; found: 275.0083. Preparation of Methyl (_E)-5-(2-Cyclopentenyl)-3-trimethylstannyl-2-pentenoate (95) Me3Sn Following general procedure C, methyl 5-(2-cyclopentenyl)-2-pentynoate (57) (53.4 mg, 0.3 mmol) was converted into 86.2 mg (84%) of the ester 95_ (air-bath d i s t i l l a t i o n temperature 85-92°C/0.2 T o r r ) . This c o l o r l e s s o i l exhibited i r ( f i l m ) : 3030, 1710, 1590, 1170, 775 cm - 1; *H nmr (80 MHz, CDC1 3) 6: 0.20 (s, 9H, -SnMe3, J s n _ H = 52/54 Hz), 1.2-1.7 (m, 4H), 1.8-2.5 (m, 2H, r i n g a l l y l i c methylene protons), 2.5-2.8 (m, IH, ring methine proton), 2.95 (t of d, 2H, y~protons, J_ = 8, 1 Hz), 3.72 (s, 3H, -OCH3), 5.6-5.8 (m, 2H, r i n g o l e f i n i c protons), 5.97 ( t , IH, a-proton, = 1 Hz, JjSn-H = 7 3 Hz). Exact Mass calcd. for C 1 3 H 2 i 0 2 S n (M+-CH3): 329.0564; found: 329.0562. - 155 -Preparation of Methyl (Z)-5-(2-Cyclopentenyl)-3-trimethylstannyl-2-pentenoate (96) Following general procedure D outlined above, methyl 5-(2-cyclopentenyl)-2-pentynoate (57) (53.0 rag, 0.3 mmol) was converted into a mixture of the (E) and (Z) pentenoates _95_ and 96_ i n a r a t i o of 2:98 (glc a n a l y s i s ) , respectively. Subjection of the mixture to column chromatography on s i l i c a gel (8 g, e l u t i o n with petroleum ether-ether, 100:1) afforded, a f t e r concentration of the appropriate (Rf = 0.38) f r a c t i o n s and d i s t i l l a t i o n (air-bath temperature 90-100°C/0.2 Torr) of the resultant o i l , 79.0 mg (77%) of the pure (Z) isomer 96_ as a c o l o r l e s s l i q u i d . This material exhibited i r ( f i l m ) : 1700, 1595, 1210, 780 cm - 1; XH nmr (80 MHz, CDC1 3) 6: 0.19 (s, 9H, -SnMe3, Js n-H = 5 3 / 5 6 Hz), 1.1-1.7 (m, 4H), 1.9-2.8 (m, 3H), 2.45 (overlapping t of d, 2H, Y-protons, J = 7.5, 1 Hz), 3.73 (s, 3H, -0CH 3), 5.6-5.8 (m, 2H, ring o l e f i n i c protons), 6.38 ( t , IH, a-proton, J_ = 1 Hz, Jjgn-H = H z ^ * Exact Mass calcd. for C 1 3 H 2 1 0 2 S n (M+-CH3): 329.0564; found: 329.0562. - 156 -Preparation of Methyl (E)-4-(3-Cyclohexenyl)-3-trimethylstannyl-2-butenoate (97) Following general procedure C, methyl 4-(3-cyclohexenyl)-2-hutynoate (59) (53.2 mg, 0.3 mmol) was converted Into 74.0 mg (72%) of the desired ester 97_ (air-bath d i s t i l l a t i o n temperature 85-90°C/0.8 T o r r ) . This co l o r l e s s o i l exhibited i r ( f i l m ) : 1720, 1590, 1205, 1160, 780, 660 cm"1; XH nmr (80 MHz, CDC13) 6: 0.19 (s, 9H, - SnMe3, J s n _ H = 53/55 Hz), 1.0-2.3 (m, 7H), 2.8-3.0 (m, 2H, y p r o t o n s ) , 3.69 (s, 3H, -0CH 3), 5.6-5.8 (m, 2H, ring o l e f i n i c protons), 6.05 ( t , IH, a-proton, J = 1 Hz, £sn-H = 7 3 H z ) « Exact Mass calcd. for C 1 3 H 2 i 0 2 S n (M+-CH3): 329.0564; found: 329.0560. Preparation of Methyl (Z)-4-(3-Cyclohexenyl)-3-trimethylstannyl-2-butenoate (98) Me3Sn Following general procedure D outlined above, methyl 4-(3-cyclohexenyl)-2-butynoate (59) (53.0 rag, 0.3 mmol) was transformed into - 157 -a mixture of the (E_) and (Z) butenoates 97_ and 98_, i n a r a t i o of 3:97 (glc a n a l y s i s ) , r e s pectively. Subjection of t h i s mixture to column chromatography on s i l i c a gel (8 g, e l u t i o n with petroleum ether-ether, 100:1) afforded, a f t e r concentration of the appropriate f r a c t i o n s and d i s t i l l a t i o n (air-bath temperature 84-88°C/0.65 Torr) of the resultant material, 73.0 mg (71%) of the desired (Z) isomer 98_. This c o l o r l e s s o i l exhibited i r ( f i l m ) : 1705, 1595, 1210, 780, 660 cm - 1; XH nmr (80 MHz, CDC 13) 5: 0.18 (s, 9H, -SnMe 3, J s n _ H = 53/56 Hz), 1.0-2.2 (m, 7H), 2.3-2.5 (m, 2H, y-protons), 3.73 (s, 3H, -0CH 3), 5.5-5.7 (m, 2H, ring o l e f i n i c protons), 6.33 (broad s, IH, a-proton, J S n _ B = 118 Hz). Exact Mass calcd. for C 1 3 H 2 1 0 2 S n (M +-CH 3): 329.0564; found: 329.0565. Preparation of Ethyl (E_)-4-_t-Butyldimethylsiloxy-3-trimethylstannyl-2-butenoate (99) To a cold (-78°C), s t i r r e d s o l u t i o n of the (triraethylstannyl)-added ethyl 4-_t-butyldimethylsiloxy-2-butynoate (55) (72.5 mg, 0.3 mmol) as a solution in anhydrous THF (= 0.5 mL). The reaction mixture was s t i r r e d at -78°C for 3 h. Normal workup as described in general procedure C followed by d i s t i l l a t i o n ( a ir-bath temperature 92-100°C/0.15 Me3Sn C02Et copper reagent (44) (0.39 mmol) i n 5 mL of anhydrous tetrahydrofuran was - 158 -Torr) of the crude product afforded 98.1 mg (80%) of a c l e a r , c o l o r l e s s o i l . Glc analysis (column A) of t h i s o i l showed that i t consisted of a 95:5 mixture of two components, which were separated by preparative t i c on s i l i c a gel using petroleum ether-ether (40:1) as eluant. The major component (lower band, R f = 0.31) was i d e n t i f i e d as ethyl (E_)-4-_t-butyldimethylsiloxy-3-trimethylstannyl-2-butenoate (99), based on the following: i r ( f i l m ) : 1705, 1595, 1185, 1080, 780 cm - 1; ln nmr (80 MHz, CDC13) 6: 0.15 (s, 6H, -SiMe 2), 0.26 (s, 9H, -SnMe3, Js n_ H = 53/56 Hz), 0.98 (s, 9H, -SiCMe 3), 1.35 ( t , 3H, -OCH2CH3, J = 7 Hz), 4.19 (q, 2H, -OCH^CHg, J_ = 7 Hz), 4.94 (d, 2H, -OCH2C=, J = £ Hz, iSn-H = 3 0 H z ) ' 5 , 9 4 ( c > 1 H> v i n v l proton, J = 3 Hz, J s n _ H = 72 Hz). Exact Mass calcd. for C 1 i + H 2 9 0 3 S i S n (M +-CH 3): 393.0908; found: 393.0918. The minor component (upper band, Rf = 0.37) was i d e n t i f i e d as ethy l (Z^)-4-t-butyldimethylsiloxy-3-trimethylstannyl-2-butenoate (100), based on the following: i r ( f i l m ) : 1700, 1305, 1195, 1120, 845, 780 cm"1; % nmr (80 MHz, CDC1 3) 6: 0.15 (s, 6H, -SiMe2), 0.25 (s, 9H, -SnMe3, Jsn-H = 5 4 / 5 6 H z ) » i * 0 0 (s, 9H, -SiCMe 3), 1.35 ( t , 3H, -0CH 2CH 3, J = 7 Hz), 4.25 (q, 2H, -0CH 2CH 3, £ = 7 Hz), 4.49 (d, 2H, -0CH2C=, J_ = 2.2 Hz, Js n_ H = 15 Hz), 6.70 ( t , IH, v i n y l proton, £ = 2.2 Hz, Js n_ H = 114 Hz). Exact Mass calcd. f o r C 1 ^ H 2 9 0 3 S i S n (M+-CH3): 393.0908; found: 393.0906. - 159 -Preparation of Ethyl (Z^)-4-£-butyldimethylsiloxy-3-trimethylstannyl-2-butenoate (100) Me,Sn C0 2 Et v I To a cold (-78°C), s t i r r e d s o l u t i o n of lithium (phenylthio)-(trimethylstannyl)cuprate (14) (0.39 mmol) i n 5 mL of anhydrous t e t r a -hydrofuran was added ethyl 4-t-butyldimethylsiloxy-2-butynoate (55) (72.0 mg, 0.3 mmol) as a solution i n dry THF. The reaction mixture was s t i r r e d at -78°C for 15 min and at -48°C for 4 h. Glc analysis (column A) of the crude o i l obtained a f t e r normal workup (general procedure D) indicated the presence of the expected (E) and (Z) butenoates 99_ and 100 in a r a t i o of 9:91, respectively, along with an unexpected longer retention time product. The mixture was subjected to column chromato-graphy on s i l i c a gel (8 g). El u t i o n of the column using petroleum ether-ether (40:1) as eluant gave, a f t e r concentration of the appropriate f r a c t i o n s and d i s t i l l a t i o n ( a i r - b a t h temperature = 100°C/0.15 Torr) of the resultant o i l , 35.2 mg (29%) of the (Z) ester 100. Further e l u t i o n of the column gave a small amount (2.9 mg, 2%) of the 05) isomer 99. These two compounds exhibited s p e c t r a l data ( i r , *H nmr) i d e n t i c a l with those described above. S t i l l further e l u t i o n of the column afforded a material which gave r i s e to the longer retention time product observed on glc analysis - 160 of the crude mixture. D i s t i l l a t i o n (air-bath temperature 125-135°C/0.15 Torr) of the material obtained from the appropriate column f r a c t i o n s afforded 36.3 mg (35%) of a viscous o i l which exhibited i r ( f i l m ) : 1695, 1580, 1200, 1110, 850 cm"1; lU nmr (80 MHz, CDCI3) 6: -0.05 (s, 6H, -SiMe 2), 0.83 (s, 9H, -SiCMe 3), 1.32 ( t , 3H, -0CH 2CH 3, J = 7 Hz), 3.91 (d, 2H, -0CH2C=, J = 2 Hz), 4.24 (q, 2H, -OCH2CH3, J = 7 Hz), 6.32 ( t , IH, v i n y l proton, J_ = 2 Hz), 7.25-7.65 (m, 5H, phenyl protons). Exact Mass calcd. for C i 8 H 2 8 0 3 S S i : 352.1528; found: 352.1529. Thus, t h i s compound i s the product of phenylthio-transfer, ethyl (Z)-4-t-butyldimethylsiloxy-3-phenylthio-2-butenoate (106). Preparation of (E)-4,4-Dimethyl-3-trimethylstannyl-2-penten-l-ol (109) To a cold (-78°C), s t i r r e d solution of ethyl (E_)-4,4-dimethyl-2-pentenoate (104) (28.2 mg, 0.09 mmol) i n 2 mL of dry pentane was added 0.25 mL (0.25 mmol) of a 1 M solution of DIBAL in hexane. The reaction mixture was s t i r r e d at -78°C for 1 h and at 0°C for 1 h. Saturated aqueous ammonium chloride (= 0.2 mL) was added and the mixture was allowed to warm to room temperature. The r e s u l t i n g white s l u r r y was treated with anhydrous magnesium sul f a t e and was then f i l t e r e d through a short column of F l o r i s i l . The column was eluted with further volumes of Me 3Sn - 161 -ether. Removal of the solvent from the combined eluate, followed by d i s t i l l a t i o n ( a i r - b a t h temperature 85-90°C/20 Torr) of the re s i d u a l material afforded 22.3 mg (91%) of the alcohol 109. This c o l o r l e s s o i l exhibited i r ( f i l m ) : 3280 (broad), 1365, 1050, 775 cm - 1; lK nmr (80 MHz, CDC1 3) 6: 0.17 (s, 9H, -SnMe3, J s n _ H = 50/52 Hz), 1.15 (s, 9H, -CMe 3), 1.37 ( t , IH, exchangeable with D20, -OH, J = 6 Hz), 4.42 (d of d, 2H, -CH20H, J = J ' = 6 Hz), 5.57 ( t , IH, o l e f i n i c proton, J_ = 6 Hz, i n - H = 9 0 H z ) * Exact Mass calcd. for C gH 1 90Sn (M+-CH 3): 263.0458; found: 263.0458. D. Synthesis and Transmetalation of Alkyl (E)-2,3-Bis-(trimethylstannyl)-2-alkenoates General Procedure E: Preparation of A l k y l (E_)-2,3-Bis-(trimethylstannyl)-2-alkenoates (115). Reaction of a,6-Acetylenic Esters with Excess (Trimethylstannyl)copper Me3Sn COaR' H R / ^SnMe, To a cold (-48°C), s t i r r e d s o l u t i o n of the (trimethylstannyl)-copper reagent (44) (0.75 mmol) i n 5 mL of anhydrous tetrahydrofuran was added the appropriate acetylenic ester (0.3 mmol) as a solu t i o n i n = 0.5 - 162 -mL of dry THF. The r e s u l t i n g dark red so l u t i o n was s t i r r e d at -48°C f o r 30 min and at 0°C for 3 h. Saturated basic aqueous ammonium chloride (1 mL) and ether (30 mL) were added and the r e s u l t i n g mixture was allowed to warm to room temperature with vigorous s t i r r i n g . S t i r r i n g was maintained for several minutes u n t i l the organic layer became clear and the aqueous layer became deep blue. The organic layer was separated, washed with saturated basic aqueous ammonium chlo r i d e , dried over anhydrous magnesium s u l f a t e , and concentrated under reduced pressure. Hexaraethylditin was removed from the residual o i l eit h e r by column chromatography (lower-boiling esters) or d i s t i l l a t i o n ( h i g h e r - b o i l i n g esters) and the desired ester was p u r i f i e d by bulb-to-bulb (Kugelrohr) d i s t i l l a t i o n . General Procedure F: Preparation of A l k y l (E_)-2,3-BIs-(trimethylstannyl)-2-alkenoates (115). Reaction of a,S-Acetylenic Esters with Excess Lithium (3-Methoxy-3-methyl-l-butynyl)- (trimethylstannyl)cuprate This procedure was i d e n t i c a l with general procedure E except that l i t h i u m (3-methoxy-3-methyl-l-butynyl)(trimethylstannyl)cuprate (45) (0.75 mmol) was used i n place of the (trimethylstannyl)copper reagent (44). - 163 -Preparation of Ethyl (E)-2,3-Bis(trimethylstannyl)-2-butenoate (114) Me 3Sn C0 2 Et Me SnMe, a) Using the (trimethylstannyl)copper reagent (44) Following general procedure E outlined above, ethyl 2-butynoate (33.6 mg, 0.3 mmol) was allowed to react with the (trimethylstannyD-copper reagent (44) (0.75 mmol) in 5 mL of anhydrous THF at -48°C for 30 min and at 0°C for 3 h. Normal workup gave a l i g h t yellow o i l which, on the basis of glc (column A) analysis, contained hexamethylditin and the desired ester 114. This material was chromatographed on s i l i c a gel (3 g) using petroleum ether-ether, 100:1 as eluant. Hexamethylditin was eluted with the solvent front and discarded. Further e l u t i o n of the column gave, a f t e r concentration of the appropriate f r a c t i o n s and d i s t i l l a t i o n (air-bath temperature 68-75°C/0.1 Torr) of the res i d u a l material, 97.2 mg (73%) of eth y l (E)-2,3-bis(trimethylstannyl)-2-butenoate (114) as a co l o r l e s s o i l . This material exhibited i r ( f i l m ) : 1680, 1230, 775 cm - 1; LH nmr (80 MHz, CDCI3) 6: 0.15 (s, 9H, -SnMe3, i n - H = 5 2 / 5 4 H z ) ' 0 , 2 6 ( s ' 9 H » "SnMe3, J s n _ H = 53/55 Hz), 1.28 ( t , 3H, -OCH2CH3, J = 7 Hz), 2.22 (s, 3H, v i n y l methyl, J a-s n-H = 1 1 H z ' Jp-Sn-H = 47/49 Hz), 4.17 (q, 2H, -OCH2CH3, J = 7 Hz). Exact Mass calcd. for C 1 1 H 2 3 0 2 S n 2 (M+-CH3): 426.9742; found: 426.9736. - 164 -b) Using the (trimethylstannyl)cuprate reagent 45_ Following general procedure F outlined above, there was obtained 98.3 mg (74%) of the desired ester 114 from 33.5 mg (0.3 mmol) of eth y l 2-butynoate. This material exhibited spectral ( i r , *H nmr) data i d e n t i -o c a l with those reported above. c) Large scale To a cold (-63°C), s t i r r e d solution of the (tr i m e t h y l s t a n n y l ) -copper reagent (44) (25 mmol) i n 150 mL of anhydrous THF was added ethyl 2-butynoate (1.12 g, 10 mmol) as a solution i n 5 mL of anhydrous THF. The reaction mixture was s t i r r e d at -63°C for 30 min, at -48°C for 30 min, and at 0°C for 3 h. Saturated aqueous basic (pH 8) ammonium chloride (1 mL) was added and the mixture was poured into a vigorously s t i r r e d mixture of ether (200 mL) and saturated aqueous basic ammonium chloride (100 mL). After several minutes, the layers were separated and the aqueous layer was extracted with ether (2 x 50 mL). The combined organic extracts were washed with saturated aqueous basic ammonium chloride (50 mL), dried over anhydrous magnesium s u l f a t e , and concentra-ted under reduced pressure to y i e l d a dark yellow o i l . The o i l was fl a s h chromatographed on s i l i c a gel (35 g) using petroleum ether-ether (50:1) as eluant. The fra c t i o n s containing the desired compound were pooled and concentrated. The remaining l i q u i d was f r a c t i o n a l l y d i s t i l -l e d (Kugelrohr) to y i e l d a small forerun of hexamethylditin (air-bath temperature <70°C/0.3 Torr) followed by 3.72 g (84%) of the desired ester 114 (air-bath temperature 84-88°C/0.3 Torr) as a c o l o r l e s s o i l . - 165 -This material exhibited s p e c t r a l data i d e n t i c a l with those reported above and also gave a s a t i s f a c t o r y combustion a n a l y s i s . Anal, calcd. for C 1 2H 2602 S r i2 : C 32.78, H 5.96; found: C 32.82, H 6.04. Preparation of Ethyl (E^)-2,3-Bis(trimethylstannyl)-2-pentenoate (116) Me 3Sn C0 2 Et SnMe, a) Using the (trimethylstannyl)copper reagent (44) Following general procedure E outlined above, ethyl 2-pentynoate (38.0 mg, 0.3 mmol) was converted into 108 mg (79%) of the ester 116 (air-bath d i s t i l l a t i o n temperature 75-80°C/0.1 T o r r ) . This c o l o r l e s s o i l exhibited i r ( f i l m ) : 1680, 1220, 1040, 775 cm - 1; XH nmr (80 MHz, CDC13) 6: 0.12 (s, 9H, -SnMe3, Jgn-H = 52/54 Hz), 0.22 (s, 9H, -SnMe3, £Sn-H = 53/55 Hz), 0.93 ( t , 3H, -CCH 2CH 3, J = 7 Hz), 1.25 ( t , 3H, -0CH 2CH 3, J = 7 Hz), 2.47 (q, 2H, -CCH 2CH 3, J = 7 Hz, J_sn-H = 6 2 H z ) > 4.13 (q, 2H, -OCH2CH3, J = 7 Hz). Exact Mass calcd. for C 1 2H 2502Sn2 (M +-CH 3): 440.9899; found: 440.9900. b) Using the (trimethylstannyl)cuprate reagent 45 Following general procedure F outlined above, there was obtained 104 mg (76%) of the desired ester 116 from 37.8 mg (0.3 mmol) of et h y l 2-pentynoate. This material exhibited s p e c t r a l ( i r , *H nmr) data - 166 -i d e n t i c a l with those reported above. Preparation of Methyl (E_)-2,3-Bis(triraethylstannyl)-4-methyl-2-pentenoate (117) Me 3Sn C0 2 Me SnMe 3 a) Using the (trimethylstannyl)copper reagent (44) Following general procedure E outlined above, methyl 4-methyl-2-pentynoate (37.8 mg, 0.3 mmol) was allowed to react with the ( t r i m e t h y l --48°C for 30 min and at 0°C for 3 h. Normal workup afforded an o i l which, on the basis of glc (column A) analysis, contained hexamethyl-d i t i n and the desired product. Hexamethylditin was removed by d i s t i l l a -tion (air-bath temperature <70°C/15 Torr) and the residual o i l was d i s t i l l e d (air-bath temperature 78-85°C/0.1 Torr) to give 96 mg (70%) of the ester 117 as a c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 1685, 1220, 780 cm"1; :H nmr (80 MHz, CDC1 3) 6: 0.18 (s, 9H, -SnMe3, J s n _ H = 52/54 Hz), 0.22 (s, 9H, -SnMe3, J s n _ H = 53/55 Hz), 1.07 (d, 6H, -CHMe_2, J = 7 Hz), 2.64 (septet, IH, -CHMe 2 , J = 7 Hz), 3.67 (s, 3H, -0CH 3). Exact Mass calcd. for C 1 2H250 2Sn2 (M +-CH 3): 440.9899; found: 440.9860. stannyl) copper reagent (44) (0.75 mmol) i n 5 mL of anhydrous THF at - 167 -b) Using the (trimethylstannyl)cuprate reagent h5_ Following general procedure F outlined above, there was obtained from 38.0 mg (0.3 mmol) of methyl 4-methyl-2-pentynoate, 101 mg (74%) of the desired ester 117 as a co l o r l e s s o i l . The lU nmr (80 MHz, CDC13) spectrum of th i s material was i d e n t i c a l with that reported above. Preparation of Methyl (E_)-2,3-Bis(trimethylstannyl-2-nonenoate (118) a) Using the (trimethylstannyl)copper reagent (44) Following general procedure E outlined above, methyl 2-nonynoate (50.4 mg, 0.3 mmol) was converted into 118 mg (79%) of the b i s -(trimethylstannyl) ester 118 (ai r - b a t h d i s t i l l a t i o n temperature 95-102°C/0.2 T o r r ) . This o i l exhibited i r ( f i l m ) : 1685, 1230, 780 cm - 1; XH nmr (80 MHz, CDCI3) 6: 0.14 (s, 9H, -SnMe3, Jsn-H = 52/54 Hz), 0.22 (s, 9H, -SnMe3, J S n - H = 5 3 / 5 5 H z ) » ° ' 7 3 (broad t, 3H, -CH 2CH 3, J = 7 Hz), 1.0-1.5 (m, 8H), 2.3-2.6 (m, 2H, y-protons), 3.69 (s, 3H, -OCH3). Exact Mass calcd. for C 1 5H 3 102Sn2 (M +-CH 3): 483.0368; found: 483.0353. b) Using the (trimethylstannyl)cuprate reagent U5_ Following general procedure F described above, there was obtained 128 mg (86%) of the bis(trimethylstannyl) ester U_8 from 50.0 mg (0.3 Me,Sn C0 2 Me - 168 -mmol) of methyl 2-nonynoate. The XH nmr spectrum of this material was identical with that described above. Preparation of Methyl (E)-2,3-Bis(trimethylstannyl)-3-cyclopropyl-propenoate (119) a) Using the (trimethylstannyl)copper reagent (44) Following general procedure E outlined above, 105 mg (7 7%) of the bis(trimethylstannyl) ester 119 was i s o l a t e d ( a i r - b a t h d i s t i l l a t i o n temperature 87-91°C/0.1 Torr) as a c o l o r l e s s o i l from a reaction employing 37.0 rag (0.3 mmol) of methyl cyclopropylpropynoate. This material exhibited i r ( f i l m ) : 3060, 1685, 1230, 775 cm - 1; *H nmr (400 MHz, CDC1 3) 6: 0.16 (s, 9H, -SnMe3, iSn-H = 5 2 / 5 4 H z ) > ° ' 2 5 <s> 9 H » -SnMe3, Jsn-H = 53/55 Hz), 0.52-0.58 (m, 2H, H c), 0.83-0.89 (m, 2H, H B), 1.77 (t of t, IH, H A, J^B = 8.5 Hz, J^c = 5.5 Hz), 3.68 (s, 3H, -OCH3). Exact Mass calcd. for C 1 2H230 2Sn2 (M+-15): 438.9742; found: 438.9750. b) Using the (trimethylstannyl)cuprate reagent 4_5 Reaction of methyl cyclopropylpropynoate (37.2 mg, 0.3 mmol) with the (triraethylstannyl)cuprate reagent 45_ (0.75 mmol) in 5 mL of Me 3Sn \ CO a Me - 169 -anhydrous THF at -48°C for 30 min and at 0°C for 3 h (general procedure F) afforded, a f t e r normal workup and d i s t i l l a t i o n of the residual o i l , 99 mg (73%) of the bis(trimethylstannyl) ester 119. This material was i d e n t i c a l ( i r , ^ H nmr) with that prepared as described i n (a) above. Preparation of Methyl (E_)-2,3-Bis(triraethylstannyl)-5-(2-cyclopentenyl)-2-pentenoate (120) a) Using the ( t r i m e t h y l s t a n n y l ) c o p p e r reagent (44) Following general procedure E o u t l i n e d above, methyl 5-(2-cyclo-pentenyl)-2-pentynoate (53.4 mg, 0.3 mmol) was allowed to react w i t h the (tr i m e t h y l s t a n n y D c o p p e r reagent (44) (0.75 mmol) i n 5 mL of anhydrous THF at -48°C f o r 30 min and at 0°C f o r 3 h. Normal workup afforded a c o l o r l e s s o i l which, on the basis of g l c (column A) a n a l y s i s , contained hexamethylditin and only one product. D i s t i l l a t i v e ( a i r - b a t h tempera-ture <70°C/0.1 Torr) removal of hexamethylditin followed by d i s t i l l a t i o n ( a i r - b a t h temperature 125-132°C/0.15 Torr) of the r e s i d u a l o i l gave 116 mg (76%) of the desired e s t e r 120 as a c o l o r l e s s o i l . This m a t e r i a l e x h i b i t e d i r ( f i l m ) : 3030, 1680, 1230, 775 cm - 1; lU nmr (400 MHz, CDC13) 6: 0.15 (s, 9H, -SnMe3, J s n _ H = 53/55 Hz), 0.25 (s, 9H, -SnMe3, - 170 -Jgn-H = 53/55 Hz), 1.35-1.50 (m, 2H, H A), i r r a d i a t i o n at 6 2.51 (Hp) s i m p l i f i e d this s i g n a l into the AB part of an ABX system (A<5 = 0.06, JAA' " 1 4 H z » iAF = 5 Hz, J^tp = 6 Hz), 1.50-1.61 (m, IH, H B), i r r a d i a t i o n at 6 2.34 (H D) or 6 2.70 (Hp) s i m p l i f i e d t h i s s i g n a l , 2.00-2.12 (m, IH, He), i r r a d i a t i o n at 6 2.34 (H D) or 6 2.70 (H F) s i m p l i f i e d t h i s s i g n a l , 2.24-2.44 (m, 2H, H D), 2.49-2.55 (m, 2H, H E, isn-H = I 4 , 30 Hz), 2.65-2.75 (m, IH, H p), 3.72 (s, 3H, -0CH 3), 5.6-5.8 (m, 2H, v i n y l protons). Exact Mass calcd. f o r C 1 6H 290 2Sn (M +-CH 3): 493.0212; found: 493.0244. b) Using the (trimethylstannyl)cuprate reagent 45 Following general procedure F outlined above, there was obtained 108 mg (72%) of the expected bis(trimethylstannyl) ester 120 from 52.8 mg (0.3 mmol) of methyl 5-(2-cyclopentenyl)-2-pentynoate. This material was i d e n t i c a l ( i r , *H nmr) with that prepared as described i n (a) above. Preparation of Methyl (E_)-2,3-Bis(trimethylstannyl)-4-(3-cyclohexenyl)-2-butenoate (121) a) Using the (trimethylstannyl)copper reagent (44) Following general procedure E outlined above, methyl 4-(3-- 171 -cyclohexenyl)-2-butynoate (59) (53.4 mg, 0.3 mmol) was converted into 125 mg (82%) of the bis(trimethylstannyl) ester 121 ( a i r - b a t h d i s t i l l a -t i o n temperature 120-125°C/0.1 T o r r ) . This material slowly c r y s t a l l i z e d (mp 46.5-47.0°C) and exhibited i r (CHC1 3): 1685, 1230, 780 cm - 1; XH nmr (80 MHz, CDC 13) 6: 0.18 (s, 9H, -SnMe3, J s n - H = 52/54 Hz), 0.27 (s, 9H, -SnMe3, J_sn-H = 53/55 Hz), 1.1-2.2 (m, 7H), 2.4-2.6 (m, 2H, y-protons), 3.73 (s, 3H, -OCH3), 5.6-5.8 (m, 2H, o l e f i n i c protons). Exact Mass calcd. for C 1 6H290 2Sn 2 (M +-CH 3): 493.0212; found: 493.0244. Anal, calcd. for C 1 7 H 3 2 0 2 S n 2 : C 40.37, H 6.38; found: C 40.53, H 6.26. b) Using the (trimethylstannyl)cuprate reagent 45 Following general procedure F outlined above, methyl 4-(3-cyclo-hexenyl)-2-butynoate (53.4 mg, 0.3 mmol) was converted into 125 mg (82%) of the ester 121, which was i d e n t i c a l ( i r , *H nmr) with the ester prepared as described i n (a) above. Preparation of Ethyl (E_)-2,3-3is(trimethylstannyl)-4-t-butyldimethyl-siloxy-2-butenoate (122) Me3Sn C02Et SnMe 3 a) Using the (trimethylstannyl)copper reagent (44) Following general procedure E outlined above, ethyl 4-j^-butyl-- 172 -dimethylsiloxy-2-butynoate (71.8 mg, 0.3 mmol) was converted into 126 mg (74%) of the bis(trimethylstannyl) ester 122_ (air-bath d i s t i l l a t i o n temperature 121-128°C/0.1 T o r r ) . This material exhibited i r ( f i l m ) : 1685, 1220, 850, 780 cm"1; LH nmr (80 MHz, CDC1 3) 6: 0.06 (s, 6H, SiMe 2), 0.16 (s, 9H, -SnMe3, Js n-H = 5 3 / 5 5 ^ » ° « 2 6 < s» 9 H> "SnMe3, iSn-H - 53/55 Hz), 0.88 (s, 9H, -SiCMe 3), 1.28 ( t , 3H, -OCH2CH3, J = 7 Hz), 4.14 (q, 2H, -OCH2CH3, _J = 7 Hz), 4.38 (s, 2H, y-protons). Exact Mass calcd. for C 1 7 H 3 7 0 3 S i S n 2 (M+-CH3): 557.0557; found: 557.0546. b) Using the (triraethylstannyDcuprate reagent 45 Following general procedure F outlined above, there was obtained 119 mg (70%) of the bis(trimethylstannyl) ester J_22_ from 72.2 mg (0.3 mmol) of acetylenic ester 55. This material exhibited spectra ( i r , H nmr) identical with those described above. Preparation of Methyl (E)-2,3-Bis( trimethylstannyl)-5-_t-butyl-diraethylsiloxy-2-pentenoate (123) Me 3 Sn C0 2 M e . I f SnMe 3 4-SiO ' I a) Using the (trimethylstannyDcopper reagent (44) Following general procedure E outlined above, methyl 5-t^butyl-dimethylsiloxy-2-pentynoate (70.7 mg, 0.3 mmol) was converted into 124 - 173 -mg (72%) of the expected ester 123 (air-bath d i s t i l l a t i o n temperature 103-107°C/0.2 T o r r ) . The c o l o r l e s s o i l exhibited i r ( f i l m ) : 1680, 1230, 1195, 840, 780 cm - 1; lH nmr (80 MHz, CDC 13) 6: 0.01 (s, 6H, -SiMe 2), 0.12 (s, 9H, -SnMe3, J s n _ H = 52/54 Hz), 0.22 (s, 9H, -SnMe3, iSn-H = 53/55 Hz), 0.86 (s, 9H, -SiCMe 3), 2.72 ( t , 2H, y-protons, J = 7 Hz), 3.55 ( t , 2H, -0CH2-, J = 7 Hz), 3.69 (s, 3H, -OCH3). Exact Mass calcd. for C 1 7 H 3 7 0 3 S i S n (M+-CH3): 557.0557; found: 557.0557. b) Using the (trimethylstannyl)cuprate reagent 45 Following general procedure F, there was obtained 118 mg (69%) of the bis( trimethylstannyl) ester 123 from 72.5 mg (0.3 mmol) of the acetylenic ester 88. The *H nmr spectrum of th i s material was i d e n t i c a l with that of the material obtained as described i n (a) above. Preparation of Methyl (E_)-2,3-Bis(trimethylstannyl)propenoate (125) and Methyl 3,3-Bis(trimethylstannyl)propanoate (126) Me 3Sn C0 2 Me Me.Sn X / * H SnMe 3 Me aSn CO aMe a) Using the (trimethylstannyl)copper reagent (44) Following general procedure E outlined above, methyl propynoate (25.0 mg, 0.3 mmol) was allowed to react with the (tr i m e t h y l s t a n n y l ) -copper reagent (44) (0.75 mmol) in 5 mL of anhydrous THF at -48°C for 30 - 174 -min and at 0°C for 3 h. Normal workup afforded a dark yellow o i l which, on the basis of glc (column A) analysis, contained hexamethylditin and a mixture of two products i n a r a t i o of 75:25. This material was subjected to preparative t i c on s i l i c a gel using petroleum ether-ether (100:1) as eluant. D i s t i l l a t i o n (air-bath temperature 110-115°C/15 Torr) of the major, less polar (Rf = 0.65) product gave 51.2 mg (41%) of. a c o l o r l e s s o i l . This material was I d e n t i f i e d as the desired b i s -(trimethylstannyl) ester 125, based on the following data. I r ( f i l m ) : 1690, 1255, 1205, 1180, 775 cm - 1; XH nmr (80 MHz, CDC1 3) 6: 0.17 (s, 9H, -SnMe3, J s n - H = 53/55 Hz), 0.19 (s, 9H, -SnMe3, J s n _ H = 54/56 Hz), 3.76 (s, 3H, -OCH3) , 7.47 (s, IH, o l e f i n i c proton, I s n _ H = 88/92 Hz). Exact Mass calcd. for C 9 H 1 9 0 2 S n 2 (M +-CH 3): 398.9429; found: 398.9456. The minor, more polar (R f = 0.44) product (15 mg, 12%), p u r i f i e d by d i s t i l l a t i o n (air-bath temperature 108-115°C/15 To r r ) , was obtained as a c o l o r l e s s o i l . This material was i d e n t i f i e d as the bis(trimethylstannyl) ester 126, based on the following data. Ir ( f i l m ) : 1730, 1200, 1160, 770 cm - 1; XH nmr (80 MHz, CDCI3) 6: 0.08 (s, 18H, -SnMe3, J ^ - H = 50/52 Hz), 0.73 ( t , IH, -CH, J = 7 Hz, J s n _ H = 21 Hz), 2.77 (d, 2H, -0CCH2-, J = 7 Hz, Jsn-H = 6 9 Hz). 3 « 6 5 (s, 3H, -OCH3) . Exact Mass calcd. for C 9 H 2 1 0 2 S n 2 (M +-CH 3): 400.9585; found: 400.9568. b) Using the (trimethylstannyl)cuprate reagent 45 Following general procedure F, there was obtained from 25.1 mg (0.3 mmol) of methyl propynoate an o i l which contained a mixture of the - 175 -esters 125 and 126 in a r a t i o of 76:24 (glc a n a l y s i s ) , r e s p e c t i v e l y . P u r i f i c a t i o n of the mixture as described i n (a) above afforded 55.8 rag (45%) of ester 125 and 15.0 mg (12%) of ester 126. These materials exhibited spectra ( i r , *H nmr) i d e n t i c a l with those described above. General Procedure G: Transmetalation of Ethyl (E_)-2,3-Bis(trimethyl-stannyl)-2-butenoate and Reaction of the Intermediate with E l e c t r o p h i l e s To a cold (-98°C), s t i r r e d s o l u t i o n of ethyl (E)-2,3-bis-(trimethylstannyl)-2-butenoate (0.1 mmol) in 5 mL of anhydrous t e t r a -hydrofuran was added methyllithium (0.11 mmol) as a solution i n ether. The r e s u l t i n g dark yellow solution was s t i r r e d at -98°C for 20 rain. The appropriate e l e c t r o p h i l e (0.13 mmol) was added and the reaction mixture was s t i r r e d at -98°C for 30 min and at -78°C for 1 h. Saturated aqueous ammonium chloride (- 0.2 mL) and ether (20 mL) were added and the mixture was allowed to warm to room temperature. The organic layer was washed with saturated aqueous ammonium chloride ( 3 x 3 mL), dried over anhydrous magnesium s u l f a t e , and concentrated under reduced pressure. The r e s u l t i n g o i l was either simply d i s t i l l e d or subjected to prepara-tive t i c and d i s t i l l a t i o n to af f o r d pure product. Preparation of Ethyl U)-2-Methyl-3-trimethylstannyl-2-butenoate (138) Me3Sn C02Et Me Me - 176 -a) Small scale To a cold (-98°C), s t i r r e d s o l u t i o n of eth y l (E)-2,3-bis-(trimethylstannyl)-2-butenoate (114) (44 mg, 0.10 mmol) i n 5 mL of dry THF was added methyllithium (0.11 mmol) as a solution in ether. The dark yellow so l u t i o n was s t i r r e d at -98°C for 20 min. Iodomethane (8 uL, 0.13 mmol) was added and the reaction mixture was s t i r r e d at -98°C for 30 min and at -78°C for 1 h. Normal workup, as described i n general procedure G, followed by d i s t i l l a t i o n (air-bath temperature 95-100°C/12 Torr) of the residual o i l afforded 21 mg (72%) of methylated ester 138 as a c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 1685, 1585, 1280, 775 cm - 1; lR nmr (80 MHz, CDC1 3) 6 : 0.08 (s, 9H, -SnMe3, Js n-H = 53/55 Hz), 1.27 ( t , 3H, -OCH2CH3, J = 7 Hz), 1.93 (q, 3H, cz-CH3, J * 1 Hz), 2.01 (q, 3H, 8-CH3, J » 1 Hz, J g n _ H = 49 Hz), 4.18 (q, 2H, -0CH 2CH 3, J = 7 Hz). Exact Mass calcd. for C 9H 1 70 2Sn (M+-CH3): 277.0250; found: 277.0246. b) Large scale To a cold (-98°C), s t i r r e d solution of the bis(trimethylstannyl) ester 114 (435 mg, 0.99 mmol) in 30 mL of dry THF was added methyl-l i t h i u m (1.1 mmol) as a solution i n ether. The reaction was allowed to proceed at -98°C for 20 rain before iodomethane (81 uL, 1.3 mmol) was added. The reaction mixture was s t i r r e d at -98°C for 30 min and at -78°C for 1 h. Normal workup, followed by d i s t i l l a t i o n ( a i r - b a t h temperature = 100°C/12 Torr) of the residual o i l afforded 247 mg (85%) of the desired ester 138 as a co l o r l e s s o i l . The *H nmr spectrum of - 177 -t h i s material was i d e n t i c a l with that described above. Preparation of Ethyl 0D-2-(2-Propenyl)-3-trimethylstannyl-2-butenoate Following general procedure G described above, the b i s ( t r i m e t h y l -stannyl) ester 114 (44 mg, 0.10 mmol) i n 5 mL of dry THF at -98°C was allowed to react with methyllithium (0.11 mmol) at -98°C for 20 min, and the resultant intermediate was allowed to react with 3-broraopropene (11 uL, 0.13 mmol) 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 80-86°C/15 Torr) of the re s i d u a l o i l afforded 25.3 mg (79%) of the ester 142 as a c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 3060, 1680, 1280, 775 cm"1; LH nmr (80 MHz, C D C 1 3 ) 6: 0.10 (s, 9H, -SnMe3, Js n-H = 53/55 Hz), 1.25 ( t , 3H, -OCH2CH3, J = 7 Hz), 2.03 (s, 3H, vin y l - C H 3 , J ^ - H = 50 Hz), 3.19 (broad d, 2H, H A, Jjjy = 6 Hz), 4.17 (q, 2H, - O C H 2 C H 3 , J = 7 Hz), 5.94 (d of d, IH, H B, J g c = 2 Hz, Jgn = 9 Hz) and (d of d, IH, H C, JBC = 2 H Z , J c d = 17 Hz), 6.82 (d of d of t, IH, H D, J B n = 9 Hz, J_£j) = 17 Hz, Jjyj = 6 Hz). Exact Mass calcd. for C 1 1 H 1 9 0 2 S n (M +-CH 3): 303.0407; found: 303.0406. (142) Me 3Sn C0 2 Et - 178 -P r epa r a t i on of E t h y l U ) - 2 - B e n z y l - 3 - t r i m e t h y l s t a n n y l - 2 - b u t e n o a t e (143) To a co ld ( -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 ) e s t e r 114 (44 mg, 0.10 mmol) i n 5 mL of anhydrous THF was added methy l -l i t h i u m (0.11 mmol) as a s o l u t i o n i n e the r . The dark, ye l l ow s o l u t i o n was s t i r r e d at -98°C f o r 20 rain. Benzyl bromide (15 uL, 0.13 mmol) was added and the r e a c t i o n mixture was s t i r r e d at -98°C f o r 30 min and at -78°C f o r 1 h. Normal workup, as o u t l i n e d i n genera l procedure G, a f f o rded a c o l o r l e s s o i l which, on the bas i s of g l c (column A) a n a l y s i s , conta ined benzy l bromide and one other component. Sub jec t i on of t h i s m a t e r i a l to p repa ra t i ve t i c ( s i l i c a g e l , double e l u t i o n w i t h petroleum e t h e r - e t h e r , 100:1) f o l l owed by d i s t i l l a t i o n ( a i r - b a t h temperature 74-77°C/0.1 Tor r ) a f f o rded 28 mg (76%) of the de s i r ed product as a c o l o r l e s s o i l . This m a t e r i a l e x h i b i t e d i r ( f i l m ) : 1685, 1600, 1580, 1280, 1200, 780, 750, 705 c m " 1 ; XH nmr (80 MHz, CDC1 3) 6: 0.13 ( s , 9H, -SnMe 3 , Jsn-a = 53/55 Hz) , 1.17 ( t , 3H, -OCH 2 CH 3 , J = 7 Hz ) , 2.12 ( s , 3H, v i n y l methy l , Jgn-n = 49 Hz ) , 3.82 ( s , 2H, -CT^Ph), 4.13 (q , 2H, -OCH 2 CH 3 , 1 = 7 Hz ) , 7.0-7.3 (m, 5H, phenyl p ro ton s ) . Exact Mass c a l c d . f o r C 1 5 H 2 1 0 2 S n (M+-CH 3): 353.0563; found: 353.0555. Me3Sn C 0 2 E t Me Ph - 179 -Preparation of Ethyl (Z)-2-(l-Hydroxycyclohexyl)-3-trimethylstannyl-2-butenoate (144) Following general procedure G outlined above, the b i s ( t r i m e t h y l -stannyl) ester 114 (38.5 mg, 0.09 mmol) was allowed to react with methyllithium (0.10 mmol) and the r e s u l t i n g intermediate was treated with cyclohexanone (11 uL, 0.12 mmol). Normal workup afforded a l i g h t yellow o i l which was subjected to preparative t i c on s i l i c a gel ( e l u t i n g solvent: petroleum ether-ether, 5:1). D i s t i l l a t i o n ( air-bath tempera-ture 82-86°C/0.06 Torr) of the material obtained from the major band (Rf = 0.39) afforded a viscous c o l o r l e s s o i l (23.2 mg, 71%). This material exhibited i r ( f i l m ) : 3450, 1700, 770 cm - 1; lU nmr (80 MHz, C D C 1 3 ) 5: 0.11 (s, 9H, -SnMe3, J s n _ H - 52/54 Hz), 1.28 ( t , 3H, -OCH2CH3, J = 7 Hz), 1.4-1.9 (m, 11H), 2.20 (s, 3H, v i n y l methyl, J s n _ H = 52 Hz), 4.15 (q, 2H, -OCH2CH3, J = 7 Hz). Exact Mass calcd. for C 1i tH 2 50 3Sn (M +-CH 3): 361.0826; found: 361.0828. Preparation of Ethyl (Z)-2-Butyl-3-trimethylstannyl-2-butenoate (145) Me 3Sn C0 2 Et 1 Me Me 3Sn C0 2 Et - 180 To a cold (-98°C), s t i r r e d s o l u t i o n of the bis(trimethylstannyl) ester 114 (44 mg, 0.10 mmol) i n 5 mL of dry THF was added a s o l u t i o n of methyllithium (0.11 mmol) i n ether. The dark yellow s o l u t i o n was s t i r r e d at -98°C for 20 min. 1-Iodobutane (15 uL, 0.13 mmol) was added and the reaction mixture was s t i r r e d at -98°C for 15 min, at -78°C for 1 h, and at room temperature for 3 h. Normal workup (general procedure G) afforded a yellow o i l which contained, on the basis of glc (column A) analysis, a mixture of the protonated ester 30_ and the desired ester 145 i n a r a t i o of 42:58, re s p e c t i v e l y . Subjection of the mixture to preparative t i c (developing solvent: petroleum ether-ether, 100:1) followed by d i s t i l l a t i o n ( a i r - b a t h temperature 80-85°C/12 Torr) of the less polar product afforded 16.5 mg (50%) of the ester 145 as a c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 1690, 1585, 1275, 780 cm - 1; *H nmr (80 MHz, CDC1 3) 5: 0.06 (s, 9H, -SnMe3, Js n-H = 5 4 Hz), 0.7-1.0 (m, 3H, CCH 2CH 3), 1.1-1.5 (m, 4H, n o n - a l l y l i c methylene protons) and 1.23 ( t , 3H, -0CH 2CH 3, J = 7 Hz), 2.02 (s, 3H, v i n y l methyl), 2.2-2.5 (m, 2H, a l l y l i c methylene protons), 4.16 (q, 2H, -0CH 2CH 3, J = 7 Hz). Exact Mass calcd. for Ci 2H230 2Sn (M +-CH 3): 319.0720; found: 319.0723. Preparation of (Z)-2-Methyl-3-trimethylstannyl-2-buten-l-ol (139) Me Me - 181 -To a cold (-78°C), s t i r r e d solution of ethyl (Z)-2-methyl-3-trimethylstannyl-2-butenoate (138) (100 mg, 0.34 mmol) i n 5 mL of dry ether was added a solu t i o n of diisobutylalurainum hydride (0.75 mmol) i n hexane. The co l o r l e s s reaction mixture was s t i r r e d at -78°C for 1 h and at 0°C for 2 h. Saturated aqueous ammonium chloride (= 0.2 mL) was added and the mixture was allowed to warm to room temperature. Treat-ment of the resultant s l u r r y with anhydrous magnesium s u l f a t e , followed by f i l t r a t i o n through a short column of F l o r i s i l and removal of solvent from the eluate afforded a c o l o r l e s s o i l . D i s t i l l a t i o n ( air-bath temperature = 65°C/12 Torr) of this material gave 71 mg (83%) of the expected alcohol 139 as a viscous o i l which exhibited i r ( f i l m ) : 3350 (broad), 1020, 780 cm - 1; *H nmr (80 MHz, CDC1 3) 6: 0.19 (s, 9H, -SnMe3, J g n _ H = 53/55 Hz), 1.22 ( t , IH, exchanges with D 20, -CH20H, J = 6 Hz), 1.80-1.95 (m, 6H, v i n y l methyl protons), 4.12 (broad d, 2H, -CH^OH, £ = 6 Hz). Exact Mass calcd. for C 7H 1 5OSn (M +-CH 3): 235.0145; found: 235.1044. Transraetalation-Protonation of (Z)-2-Methyl-3-trimethylstannyl-2-buten-l - o l . Preparation of (E)-2-Methyl-2-buten-l-ol (140) Me Me - 182 -To a cold (-20°C) s t i r r e d solution of the alcohol 139 (16.2 mg, 0.065 mmol) i n 2 mL of dry THF was added a solution of methyllithium (0.13 mL, 0.14 mmol) i n ether. The c o l o r l e s s reaction mixture was s t i r r e d at -20°C for 1 h. Saturated aqueous ammonium chloride (1 mL) and ether (10 mL) were added and the mixture was allowed to warm to room temperature. The organic layer was separated and dried over anhydrous magnesium s u l f a t e . Removal of the solvent by c a r e f u l d i s t i l l a t i o n at atmospheric pressure followed by d i s t i l l a t i o n ( a ir-bath temperature = 60°C/12 Torr) of the res i d u a l material afforded 3.2 mg (57%) of a col o r l e s s l i q u i d . This material was homogeneous by glc (column A) and t i c (developing solvent: petroleum ether-ether, 5:1) analyses; i t s chromatographic behaviour was i d e n t i c a l with that of a sample of t i g l i c 9 3 alcohol (prepared by diisobutylalurainum hydride reduction of t i g l i c aldehyde). The *H nmr spectra of these two materials were also i d e n t i c a l . S p e c i f i c a l l y (CDC1 3, 80 MHz) 6: 1.63 (broad d, 3H, =CHCH3, J = 6 Hz), 1.67 (broad s, 3H, HC=C-CH3), 4.00 (broad s, 2H, -CH20H) , 5.3-5.7 (m, IH, o l e f i n i c proton). E. Preparation of u)-Substltuted a,B-Acetylenlc Esters and Reaction with  (Trimethylstannyl)copper Reagents Preparation of 5-Tetrahydropyranyloxy-l-pentyne (152) H-C5C-(CH2),-0THP - 183 -A mixture of 4-pentyn-l-ol (8.4 g, 100 mmol), dihydropyran (12.6 g, 150 mmol) and pyridinium p_-toluenesulfonate (PPTS) (2.5 g, 10 mmol) i n 300 mL of dry dichloromethane was s t i r r e d at room temperature for 12 h. The reaction mixture was di l u t e d with 1000 mL of ether, washed with brine (2 x 15 mL) and dried over anhydrous magnesium s u l f a t e . Removal of the solvent followed by d i s t i l l a t i o n ( a i r - b a t h temperature 95-100°C/12 Torr) of the residual yellow o i l afforded 16.0 g (95%) of the THP ether 152 as a co l o r l e s s l i q u i d . This material exhibited i r ( f i l m ) : 3280, 2090, 1140, 1120 cm"1; lR nmr (80 MHz, CDC1 3) 6: 1.3-2.1 and 1.88 (m, 8H) and ( t , IH, - C E C H , J = 1.5 Hz), 2.30 (d of t, 2H, -C=C-CH2, J_ = 6.5, 1.5 Hz), 3.3-4.1 (m, 4H, - 0 C H 2 - ) , 4.58 (broad s, IH, methine proton). Exact Mass calcd. for C i o H i 6 0 2 ! 168.1151; found: 168.1130. Preparation of Methyl 6-Tetrahydropyranyloxy-2-hexynoate (153) THP0 - (CH 2 ) 3 -CsC -C0 2 Me Following general procedure A described above, a sol u t i o n of the alkyne 152 (6.72 g, 40 mmol) in 200 mL of dry THF was treated succes-s i v e l y with a solution of methyllithium (29.9 mL, 44 mmol) i n ether and methyl chloroformate (3.71 mL, 48 mmol) under the s p e c i f i e d conditions. Normal workup, followed by bulb-to-bulb d i s t i l l a t i o n (air-bath tempera-ture 120-125°C/0.5 Torr) of the crude material provided 8.31 g (92%) of - 184 -the desired ester as a c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 2210, 1710, 1430, 1260 cm"1; lR nmr (80 MHz, C D C I 3 ) 6: 1.3-2.0 (m, 8H), 2.42 ( t , 2H, -C=C-CH2-, J = 7 Hz), 3.3-4.0 and 3.70 (m, 4H, -0CH 2-), and (s, 3H, - O C H 3 ) , 4.53 (broad s, IH, methine proton). Exact  Mass calcd. for C 1 2 H i a 0 4 : 226.1205; found: 226.1195. Preparation of Methyl 6-Hydroxy-2-hexynoate (156) H0- (CH 2 ) 3 -C5C-C0 2 Me A solution of the tetrahydropyranyl ether 153 (1.90 g, 8.4 mmol) and pyridinium p-toluenesulfonate (PPTS) 9 l + ( 0 . 2 g, 0.8 mmol) i n 50 mL of methanol was heated (70°C) for 12 h. The solvent was removed under reduced pressure and the crude material was subjected to f l a s h chroma-tography on s i l i c a gel (3 x 15 cm column; e l u t i o n with petroleum ether-ether, 1:1). Concentration of the appropriate (R f = 0.24) f r a c t i o n s followed by d i s t i l l a t i o n (air-bath temperature 102-108°C/0.2 Torr) of the r e s i d u a l material afforded 1.06 g (100%) of the hydroxy ester 156 as a viscous o i l . This material exhibited i r ( f i l m ) : 3360 (broad), 2 2 1 0 , 1705, 1260 cm - 1; XH nmr (80 MHz, C D C 1 3 ) 6: 1.33 (t of t, 2 H , -CH 2CH 2CH 2-, J = 7, 6 Hz), 2.48 ( t , 2 H , -C=C-CH2-, J = 7 Hz), 3.73 ( t , 2 H , - O C H 2 - , J = 6 Hz) and 3.76 (s, 3H, - O C H 3 ) . Exact Mass calcd. for C 7H 1 0O 3: 142.0630; found: 142.0630. - 185 -Preparation of Methyl 6-Bromo-2-hexynoate (154) Br-(CH2)3-Csc-C02Me 87 To a s t i r r e d suspension of triphenylphosphine dibromide (16.5 mmol) i n 80 mL of dry dichloromethane was added a solution of the THP ether 153 (3.39 g, 15 mmol) in 10 mL of dry dichloromethane. The r e s u l t i n g yellow solution was s t i r r e d at room temperature for 0.5 h. The reaction mixture was washed with water (2 x 40 mL) and dried over magnesium s u l f a t e . Removal of the solvent, followed by subjection of the crude material to f l a s h chromatography on s i l i c a gel (3 x 15 cm column; e l u t i o n with petroleum ether-ether, 9:1) afforded a c o l o r l e s s o i l which upon d i s t i l l a t i o n ( a i r - b a t h temperature 112-114°C/12 Torr) gave 2.34 g (74%) of the bromo ester 154 as a c o l o r l e s s l i q u i d . This material exhibited i r ( f i l m ) : 2220, 1710, 1430, 1260, 1080, 760 cm"1; XH nmr (80 MHz, CDC1 3) 6: 2.09 (t of t, 2H, - C ^ C H J C H J - , J = J ' =6 Hz), 2.53 ( t , 2H, -C=C-CH2-, J = 6 Hz), 3.49 ( t , 2H, -CH 2Br, J = 6 Hz), 3.74 (s, 3H, -OCH3). Exact Mass calcd. for C 7 H 9 8 1 B r 0 2 : 205.9765; found: 205.9790. Preparation of Methyl 6-Iodo-2-hexynoate (155) l-(CH2)3-CsC-C0 2Me - 186 -To a s t i r r e d s o l u t i o n of the bromo ester 154 (570 mg, 2.8 mmol) in 10 mL of dry acetone was added 650 mg (4.3 mmol) of anhydrous sodium iodide. The reaction mixture was s t i r r e d at room temperature for 10 h and the solvent was then removed under reduced pressure. Ether (30 mL) was added and the organic layer was washed successively with brine (5 mL), saturated sodium t h i o s u l f a t e ( 2 x 5 mL) and brine (5 mL), and dried over anhydrous magnesium s u l f a t e . Removal of the solvent, followed by d i s t i l l a t i o n ( air-bath temperature 90-95°C/0.4 Torr) of the residual o i l 9 5 provided 640 mg (91%) of the iodo ester 155 as a c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 2210, 1710, 1430, 1260, 1080, 755 cm - 1; XH nmr (80 MHz, CDC13) 6: 2.07 (t of t, 2H, -CH 2CH 2CH 2-, J = 7, 6.5 Hz), 2.51 ( t , 2H, -CEC-CH2-, J = 7 Hz), 3.29 ( t , 2H, -CH 2I, J = 6.5 Hz), 3.77 (s, 3H, -OCH3). Exact Mass calcd. for C 7H 9I0 2: 251.9647; found: 251.9653. Preparation of Methyl 6-Methanesulfonyloxy-2-hexynoate (157) MsO-(CH2),-CsC-C02Me To a cold (0°C), s t i r r e d s o l u t i o n of the hydroxy ester 156 (720 mg, 5 mmol) in 4 mL of dry pyridine was added methanesulfonyl chloride (0.46 mL, 6 mmol). The reaction mixture was s t i r r e d at 0°C for 2 h. Ice and water (40 mL) were added and the mixture was extracted with ether (2 x 40 mL). The combined organic extract was washed with saturated copper su l f a t e (2 x 10 mL) and dried over anhydrous magnesium - 187 -s u l f a t e . Removal of the solvent, followed by d i s t i l l a t i o n ( air-bath temperature = 150°C/0.7 Torr) of the residual material afforded 826 mg (75%) of the desired mesylate 157 as a l i g h t pink o i l . This material exhibited i r ( f i l m ) : 2220, 1710, 1350, 1260, 1180, 1085, 935 cm"1; -1H nmr (80 MHz, CDC1 3) 6: 1.98 (t of t, 2H, -CH 2CH 2CH 2-, J = 7, 6 Hz), 2.48 ( t , 2H, -C=C-CH2-, J = 7 Hz), 3.00 (s, 3H, -0 3SCH 3), 3.72 (s, 3H, -0CH 3), 4.27 ( t , 2H, -0CH2-, J_ = 6 Hz). Exact Mass calcd. for CyHoOi+S (M +-0CH 3): 189.0221; found: 189.0219. Preparation of Methyl 7-Tetrahydropyranyloxy-2-heptynoate (159) THP0-(CH2)4-CsC-C02Me Following general procedure A outlined above, a solution of 9 6 6-tetrahydropyranyloxy-l-hexyne (3.90 g, 21.4 mmol) i n 100 mL of dry THF was treated successively with a solution of methyllithium (19.0 mL, 27.8 mmol) i n ether and methyl chloroformate (2.5 mL, 32 mmol) under the spe c i f i e d conditions. Normal workup, followed by d i s t i l l a t i o n ( a i r - b a t h temperature 125-130°C/0.3 Torr) of the crude material provided 4.58 g (89%) of the ester 159 as a colo r l e s s o i l . This material exhibited i r ( f i l m ) : 2220, 1710, 1260 cm - 1; lR nmr (60 MHz, CDC1 3) 6: 1.3-2.1 (m, 10H), 2.36 (broad t, 2H, -C=C-CH2-, J = 7 Hz), 3.2-4.1 and 3.74 (ra, 4H, -0CH2-) and (s, 3H, -0CH 3), 4.4-4.7 (m, IH, methine proton). - 188 -Preparation of Methyl 7-Bromo-2-heptynoate (160) Br - ( C H 2 ) 4 -C5C -C0 2 Me 87 To a s t i r r e d s l u r r y of triphenylphosphine dibromide (11 mmol) i n 50 mL of dry dichloromethane was added a solu t i o n of the THP ether 159 (2.16 g, 9.0 mmol) i n 5 mL of dry dichloromethane. The reaction mixture was s t i r r e d at room temperature for 30 min and then was washed with water (2 x 25 mL) and dried over anhydrous magnesium s u l f a t e . Subjection of the crude material obtained on removal of the solvent to f l a s h chromatography on s i l i c a gel (3 x 15 cm column; e l u t i o n with petroleum ether-ether, 9:1) afforded an o i l which upon d i s t i l l a t i o n ( a ir-bath temperature =140°C/12 Torr) provided 1.76 g (89%) of the brorao ester 160 as a co l o r l e s s o i l . This material exhibited i r ( f i l m ) : 2220, 1710, 1435, 1260, 1080, 760 cm - 1; XH nmr (80 MHz, CDCI3) 6: 1.0-2.2 (m, 4H), 2.41 ( t , 2H, -C=C-CH2-, J = 6.5 Hz), 3.44 ( t , 2H, -CH 2Br, J. = 6 Hz), 3.77 (s, 3H, -OCH3). Exact Mass calcd. for C 8 H u 7 9 B r 0 2 : 217.9942; found: 217.9940. Preparation of Methyl 7-Iodo-2-heptynoate (161) l - ( C H 2 ) 4 - C s C - C O a Me - 189 -To a s t i r r e d s o l u t i o n of the bromo ester 160 (387 mg, 1.77 mmol) in 3 mL of dry acetone was added 350 mg (2.33 mmol) of sodium iodide. The r e s u l t i n g yellow s l u r r y was s t i r r e d at room temperature for 10 h. Ether (50 mL) was added and the mixture was washed successively with water (5 mL), saturated aqueous sodium t h i o s u l f a t e ( 2 x 5 mL) and water (5 mL) and then was dried over anhydrous magnesium s u l f a t e . Removal of the solvent, followed by d i s t i l l a t i o n (air-bath temperature 113-120°C/ 0.7 Torr) of the residual material afforded 425 mg (90%) of the iodo ester 161 as a c o l o r l e s s l i q u i d . This material exhibited i r ( f i l m ) : 2210, 1705, 1430, 1260, 1080, 755 cm - 1; XH nmr (80 MHz, CDC1 3) 6: 1.5-2.2 (m, 4H), 2.38 ( t , 2H, -C=C-CH2-, J = 6.5 Hz), 3.21 ( t , 2H, - C H 2 I , J_ = 6.5 Hz), 3.76 (s, 3H, - O C H 3 ) . Exact Mass calcd. for C 8 H u I 0 2 : 265.9803; found: 265.9807. Preparation of Methyl (E_)-6-Bromo-3-trimethylstannyl-2-hexenoate (162) To a cold ( -78°C), s t i r r e d s o l u t i o n of the (trimethylstannyl)-copper reagent 44_ (0.39 mmol) i n 5 mL of anhydrous THF was added a THF s o l u t i o n (0.5 mL) of methyl 6-bromo-2-hexynoate (154) (60.8 mg, 0.3 mmol). The dark red reaction mixture was s t i r r e d at -78°C for 3 h. Normal workup, as described i n general procedure C, gave a c o l o r l e s s o i l Me 3Sn - 190 -which contained, on the basis of glc (column B) analysis, hexamethyl-d i t i n and a single product. Subjection of the crude material to f l a s h chromatography on s i l i c a gel (2 x 15 cm column; e l u t i o n with petroleum ether-ether, 30:1) gave an o i l which upon d i s t i l l a t i o n (air-bath temperature 105-112°C/0.A Torr) provided 88.7 mg (81%) of the (E_) ester 162 as a col o r l e s s o i l . This material exhibited i r ( f i l m ) : 1710, 1200, 1180, 775 cm"1; *H nmr (80 MHz, CDC 13) 6: 0.22 (s, 9H, -SnMe3, Jgn-H = 53/55 Hz), 1.7-2.2 (m, 2H, -CH 2CH 2CH 2-), 3.02 (broad t, 2H, y-protons, J = 7.5 Hz), 3.43 ( t , 2H, -CH 2Br, J = 7 Hz), 3.69 (s, 3H, -OCH3), 6.03 ( t , IH, v i n y l proton, J_ = 1 Hz, J£ n_H = 71 Hz). Exact Mass calcd. for C 9 H 1 6 8 1 B r 0 2 S n (M +-CH 3): 356.9335; found: 356.9333. Preparation of Methyl (Z)-6-Brorao-3-trimethylstannyl-2-hexenoate (163) Following general procedure D outlined above, the a,B-acetylenic ester 15A (61.2 mg, 0.3 mmol) was allowed to react with lithium (phenylthio)(trimethylstannyl)cuprate (0.39 mmol) i n 5.5 mL of dry THF at -78°C for 15 min and at -A8°C for A h. Normal workup afforded a c o l o r l e s s o i l which contained, on the basis of glc (column B) analysis, hexamethylditin, several minor (= 1%) u n i d e n t i f i e d impurities, and a mixture of the (E) and (Z) hexenoates 162 and 163 i n a r a t i o of 7:93, Me 3 Sn ,C02Me - 191 -re s p e c t i v e l y . Subjection of the crude o i l to column chromatography on s i l i c a gel (15 g, e l u t i o n with petroleum ether-ether, 50:1), followed by concentration of the appropriate (Rf = 0.27) f r a c t i o n s and d i s t i l l a -t i o n (air-bath temperature 93-100°C/0.2 Torr) of the res i d u a l material afforded 80.1 mg (72%) of the (_Z) hexenoate 163. This material e x h i b i -ted i r ( f i l m ) : 1700, 1595, 1210, 775 cm - 1; lU nmr (80 MHz, CDC1 3) 6: 0.19 (s, 9H, -SnMe3, J s n _ H = 54/56 Hz), 1.7-2.2 (m, 2H, -CH 2CH 2CH 2-), 2.59 (broad t, 2H, y-protons, J = 7 Hz), 3.39 ( t , 2H, -CH 2Br, J = 6.5 Hz), 3.74 (s, 3H, -0CH 3), 6.42 ( t , IH, v i n y l proton, J = 1 Hz, J s n _ H = 116 Hz). Exact Mass calcd. for C 9 H 1 6 8 1 B r 0 2 S n (M +-CH 3): 356.9335; found: 356.9342. Preparation of l-Carbomethoxy-2-trimethylstannyl-l-pentene (164) C 0 2 M e SnMe, a) From methyl 6-bromo-2-hexynoate (154) To a cold (-78°C), s t i r r e d solution of li t h i u m (phenylthio)-(triraethylstannyl)cuprate (0.39 mmol) i n 5 mL of dry THF was added a THF (0.5 mL) solu t i o n of methyl 6-bromo-2-hexynoate (154) (61.0 mg, 0.3 mmol). The dark, red reaction mixture was s t i r r e d at -78°C for 15 min and at -48°C for 4 h. Hexamethylphosphoramide (0.5 mL) was added and the r e s u l t i n g mixture was allowed to warm slowly to room temperature and - 192 -stirred at that temperature for 2 h. Saturated aqueous ammonium chloride (= 0.2 mL) and ether (40 mL) were added and the mixture was vigorously stirred at room temperature for 10 min. The resulting brown slurry was treated with anhydrous magnesium sulfate and filtered through a short column of F l o r i s i l . The column was washed with further volumes of ether. The combined eluate was washed successively with saturated aqueous copper sulfate ( 2 x 5 raL) and saturated basic aqueous ammonium chloride (5 mL). Drying (MgSO^) of the organic layer followed by removal of the solvent afforded a colorless o i l which contained, on the basis of glc (column B) analysis, hexamethylditin, several minor (=. 1%) unidentified impurities, and a mixture of the cyclic ester 164 and methyl (Z)-3-cyclopropyl-3-triraethylstannylpropenoate (94) in a ratio of 98:2. The latter compound was identified by co-injection with an authentic sample. Subjection of the crude o i l to flash chromatography on s i l i c a gel (3 x 15 cm column; elution with petroleum ether-ether, 100:1) followed by concentration of the appropriate fractions and d i s t i l l a t i o n (air-bath temperature 85-90°C/0.3 Torr) of the residual material afforded 66.0 mg (77%) of the desired ester 164 as a colorless o i l . This material exhibited i r (film): 1700, 1585, 1260, 770 cm-1; hi nmr (80 MHz, CDC13) 6: 0.17 (s, 9H, -SnMe3, J s n _ H = 54/56 Hz), 1.91 (quintet, 2H, J = 7 Hz), 2.63 (t, 4H, a l l y l i c protons, J = 7 Hz), 3.73 (s, 3H, -0CH3). Exact Mass calcd. for C 9H 1 50 2Sn (M+-CH3): 275.0094; found: 275.0081. - 193 -b) From methyl 6-iodo-2-hexynoate (155) This reaction was performed e s s e n t i a l l y as described f o r the corresponding bromo ester 154 in (a) above. The r a t i o (glc analysis) of the ester 164 and 94_ i n the crude product was 98:2, re s p e c t i v e l y . From 74.8 mg (0.3 mmol) of the iodo ester 155, there was obtained 59.2 rag (73%) of the c y c l i z e d ester 164. This material was chromatographically (glc and t i c ) and s p e c t r a l l y ( i r , nmr) i d e n t i c a l with the material prepared i n (a) above. c) From methyl 6-methanesulfonyloxy-2-hexynoate (157) This reaction was performed e s s e n t i a l l y as described for the corresponding bromo ester 154 i n (a) above. From 65.2 mg (0.3 mmol) of the ester 157, there was i s o l a t e d 66.8 (77%) of a c o l o r l e s s o i l which contained (glc analysis) the desired c y c l i z e d ester 164 and methyl (Z)-3-cyclopropyl-3-trimethylstannylpropenoate (94) i n a r a t i o of 86:14, respectively. Preparation of Methyl (E_)-7-Bromo-3-trimethylstannyl-2-heptenoate (317) Me 3Sn Br C0 2Me Following general procedure C outlined above, methyl 7-bromo-2-heptynoate (160) (65.0 mg, 0.3 mmol) was allowed to react with the - 194 -(trimethylstannyl)copper reagent (44) (0.39 mmol) i n 5.5 mL of dry THF at -78 °C for 3 h. Normal workup afforded a c o l o r l e s s o i l which contained, on the basis of glc (column B) analysis, hexamethylditin and only one product. Subjection of the crude o i l to f l a s h chromatography on s i l i c a gel (3 x 15 cm column; e l u t i o n with petroleum ether-ether, 30:1) followed by concentration of the appropriate (Rf = 0.35) fra c t i o n s and d i s t i l l a t i o n (air-bath temperature = 90°C/0.3 Torr) of the residual material afforded 96.0 mg (84%) of the (E) heptenoate 317 as a co l o r l e s s o i l . This material exhibited i r ( f i l m ) : 1710, 1590, 1200, 1180, 775 cm - 1; XH nmr (80 MHz, CDC13) 6: 0.22 (s, 9H, -SnMe3, Js n-H = 54 Hz), 1.4-2.1 (m, 4H), 2.93 (broad t, 2H, v-protons, J = 7.5 Hz), 3.45 ( t , 2H, -CH 2Br, J = 6.5 Hz), 3.70 (s, 3H, -0CH 3), 6.00 (broad s, IH, 81 v i n y l proton, £sn-H = 7 ^ Hz). Exact Mass calcd. for ^10^18 Br0 2Sn (M +-CH 3): 370.9492; found: 370.9529. Preparation of Methyl (Z)-7-Bromo-3-trimethylstannyl-2-heptenoate (318) Following general procedure D outlined, methyl 7-brorao-2-heptynoate (160) (65.6 mg, 0.3 mmol) was allowed to react with l i t h i u m (phenylthio) (trimethylstannyl)cuprate (14) (0.3 mmol) i n 5.5 mL of dry THF at -78°C for 15 min and at -48°C for 4 h. Normal workup afforded a Br - 195 c o l o r l e s s o i l which contained, on the ba s i s of g l c (column B) a n a l y s i s , hexamethylditin, a number of minor (= 1%) i m p u r i t i e s i n c l u d i n g the c y c l i z e d e s t e r 168, and a mixture of the (E_) and (Z) heptenoates 317 and 318 i n a r a t i o of 5:95, r e s p e c t i v e l y . Subjection of the crude o i l to f l a s h chromatography on s i l i c a g e l (3 x 15 cm column; e l u t i o n w i t h petroleum ether-ether, 100:1) gave an o i l which upon d i s t i l l a t i o n ( a i r - b a t h temperature = 90°C/0.1 Torr) fu r n i s h e d 85.9 mg (74%) of the es t e r 318 as a c o l o r l e s s o i l . This m a t e r i a l e x h i b i t e d i r ( f i l m ) : 1700, 1595, 1335, 1210, 775 cm - 1; *H nmr (80 MHz, CDC1 3) 6: 0.20 ( s , 9H, -SnMe 3, isn-H = 54/56 Hz), 1.4-2.1 (m, 4H), 2.45 (broad t , 2H, y-protons, J = 7 Hz), 3.42 ( t , 2H, -CH ?Br, J = 6 Hz), 3.73 ( s , 3H, -OCH3), 6.37 ( t , IH, v i n y l proton, J = 1 Hz, J s n _ H = 1 1 8 H z>« Exact  Mass c a l c d . f o r C L 0 H 1 8 8 1 B r O 2 S n (M +-CH 3): 370.9492; found 370.9502. L i t h i u m ( P h e n y l t h i o ) ( t r i m e t h y l s t a n n y l ) c u p r a t e Induced C y c l i z a t i o n of Methyl 7-3romo-2-heptynoate (160). Formation of Methyl ( C y c l o p e n t y l i d e n e ) ( t r i r a e t h y l s t a n n y l ) a c e t a t e (168) and Methyl (E)-2,3-Bis(triraethylstannyl)-7-bromo-2-heptenoate (169) This r e a c t i o n was performed e s s e n t i a l l y as described f o r the pre p a r a t i o n of l-carboraethoxy-2-trimethylstannyl-l-cyclopentene (164). - 196 -From 65.5 mg (0.3 mmol) of methyl 7-bromo-2-heptynoate (160), there was obtained a c o l o r l e s s o i l which contained, on the basis of glc (column B) an a l y s i s , hexamethylditin, several minor (= 1%) components, one major (>90%) component, and a small (3%) amount of the desired c y c l i z e d ester, l-carbomethoxy-2-trimethylstannyl-l-cyclohexene (167)*. The major product (39.2 rag, 43%) was i s o l a t e d by f l a s h chromatography of the crude o i l on s i l i c a gel (3 x 15 cm column; e l u t i o n with petroleum ether-ether, 100:1) followed by concentration of the appropriate f r a c t i o n s and d i s t i l l a t i o n (air-bath temperature = 60°C/0.9 Torr) of the r e s i d u a l material. The c o l o r l e s s o i l obtained was i d e n t i f i e d as the cc-trimethyl-stannyl-a,8-unsaturated ester 168 based on the following data. Ir ( f i l m ) : 1700, 1600, 1205, 1190, 775 cm"1; lK nmr (80 MHz, CDC1 3) 6: 0.24 (s, 9H, -SnMe3, Js n-H = 53/56 Hz), 1.5-1.8 (m, 4H), 2.38 (broad t, 2H, Y _ P r o t o n s trans to -C02Me, £ = 7 Hz), 2.70 (broad t 2H, y-protons c i s to -C02Me, J_ = 7 Hz), 3.70 (s, 3H, -OCH3). Exact Mass ca l c d . for C 1 0H 1 7O 2Sn (M +-CH 3): 289.0251; found: 289.0251. Also i s o l a t e d from the above column was 30.5 mg (19%) of the bis(trimethylstannyl) ester 169 as a c o l o r l e s s o i l . This material did not evoke a response on the gas chromatograph under standard condi-tio n s . It exhibited i r ( f i l m ) : 1680, 1430, 1210, 770 cm"1; lH nmr (80 * This material was i d e n t i f i e d by c o - i n j e c t i o n with an authentic sample prepared by A. Tse i n our laboratories v i a reaction of the enol tosylate of 2-(carbomethoxy)cyclohexanone with l i t h i u m phenylthlo-(trimethylstannyl)cuprate (14). - 197 -MHz, CDCI3) 6: 0.17 (s, 9H, -SnMe3, J s n _ H = 5 2 / 5 4 H z ) » ° « 2 6 (s, 9H, -SnMe3, Jgn-H = 5 3 / 5 5 H z>' l ^ 3 - 2 * ! (<n, AH), 2.51 (broad t, 2H, Y-protons, J = 7.5 Hz), 3.42 ( t , 2H, -CH 2Br, £ = 6.5 Hz), 3.72 (s, 3H, -0CH 3). Exact Mass calcd. for C 1 3 H 2 6 8 1 B r 0 2 S r i 2 (M +-CH 3): 534.9140; found: 534.9132. An e s s e n t i a l l y i d e n t i c a l reaction using methyl 7-iodo-2-heptynoate gave a crude o i l which contained, on the basis of glc (column B) analysis, the cyclopentylidene ester 168 and the 1-cyclohexene-carboxylate 167 i n a r a t i o of 95:5, res p e c t i v e l y . This mixture was not analyzed further. V. Synthesis of the Acyl Portion of Trlophamine Preparation of Ethyl (Z^-3-(Tri-n-butylstannyl)-2-pentenoate (183) To a cold (-78°C), s t i r r e d solution of li t h i u m (phenylthio)-(tri-n-butylstannyl)cuprate (181) (12.0 mmol) in 100 mL of dry THF was added a solution of ethyl 2-pentynoate (53) (1.26 g, 10 mmol) in 5 mL of dry THF. The reaction mixture was s t i r r e d at -78°C for 15 min and at -48°C for 4 h. Ethanol (1 mL) and ether (100 mL) were added and the mixture was allowed to warm to room temperature. The r e s u l t i n g yellow s l u r r y was treated with anhydrous magnesium s u l f a t e and then was n-Bu3Sn C02Et - 1 9 8 -f i l t e r e d through a short column of F l o r i s i l . The column was washed with further volumes of ether. The combined eluate was concentrated to af f o r d a yellow o i l which contained, on the basis of glc (column A) anal y s i s , t e t r a - n - b u t y l t i n , hexa-n-butylditin, and a mixture of eth y l (Z)- and (E_)-3-(tri-ri-butylstannyl)-2-pentenoate (183) and (184), i n a r a t i o of 97:3, respectively. Subjection of t h i s material to column chromatography on s i l i c a gel (150 g, el u t i o n with petroleum ether-ether, 100:1) provided an o i l which upon d i s t i l l a t i o n ( air-bath temperature 128-135°C/0.3 Torr) gave 3.18 g (76%) of the pure (Z) pentenoate 183 as a co l o r l e s s l i q u i d . This material exhibited i r ( f i l m ) : 1700, 1595, 1200, 880 cm - 1; LH nmr (80 MHz, CDC13) 6: 0.7-1.8 (m, 33H), 2.42 (d of q, 2H, y-protons, _J = 1.5, 7.5 Hz, Jsn-H = 5 3 H z ^ » 4 , 1 7 ^ ' 2 H ' -OCHjCHg, J = 7 Hz), 6.38 ( t , IH, o l e f i n i c proton, J_ = 1.5 Hz, J s n _ H = 109 Hz). Exact Mass calcd. for C 1 5H 290 2Sn (M+^Hg): 361. 1190; found: 361.1187. Preparation of Ethyl (E)-3-(Tri-n_-butylstannyl)-2-pentenoate (184) To a cold (-78°C), s t i r r e d s olution of the ( t r i - n - b u t y l s t a n n y l ) -copper reagent 182 (26 mmol) i n 200 mL of dry THF was added a solution of ethyl 2-pentynoate (5_3) (2.52 g, 20 mmol) in 10 mL of dry THF. The n-Bu3Sn - 199 -dark red reaction mixture was s t i r r e d at -78°C for 3 h. Ethanol (1 mL) , saturated aqueous ammonium chloride (pH 8, 20 mL), and ether (200 mL) were added successively and the mixture was allowed to warm to room temperature with vigorous s t i r r i n g . The layers were separated and the aqueous phase was extracted with ether. The combined extracts were washed with saturated aqueous ammonium chloride and dried over magnesium s u l f a t e . Subjection of the o i l obtained on removal of the solvent to column chromatography on s i l i c a g el (250 g, e l u t i o n with petroleum ether-ether, 100:1) afforded, a f t e r concentration of the appropriate fractions and d i s t i l l a t i o n ( air-bath temperature = 130°C/0.3 Torr) of the combined residual material, 6.92 g (83%) of the ester 184 as a col o r l e s s o i l . This material exhibited i r ( f i l m ) : 1710, 1585, 1180, 870 cm - 1; XH nmr (80 MHz, CDC1 3) 6: 0.7-1.8 (m, 33H), 2.88 (d of q, 2H, y-protons, £ = 1.2, 7.5 Hz, Js n_ H = 56 Hz), 4.16 (q, 2H, -OCj^CHg, _J = 7 Hz), 5.92 ( t , IH, J = 1.2 Hz, Js n_ H = 65 Hz). Exact Mass calcd. for C 1 5H 2' 90 2Sn (M^Ci+Hg): 361.1190; found: 361. 1207. Preparation of (Z^-3-(Tri-n-butylstannyl)-2-penten-l-ol (185) To a cold (-78°C), s t i r r e d s o l u t i o n of the ester 183 (418 mg, 1.0 mmol) i n 12 mL of dry ether was added a solution of diisobutylalurainum - 200 -hydride (DIBAL) i n hexane (2.5 mL, 1 M, 2.5 mmol). The c o l o r l e s s s o l u t i o n was s t i r r e d at -78°C for 1 h and at 0°C for 2 h. Saturated aqueous ammonium chloride (0.5 mL) was added and the mixture was allowed to warm to room temperature. The r e s u l t i n g white s l u r r y was treated with anhydrous magnesium sulfate and then was f i l t e r e d through a short column of F l o r i s i l . The column was washed with further volumes of 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 120-125°C/0.3 Torr) of the res i d u a l o i l , afforded 339 mg (90%) of the alcohol 185 as a c o l o r l e s s o i l which showed i r ( f i l m ) : 3320, 1460, 1010 cm"1; LH nmr (80 MHz, CDCI3) 6: 0.8-1.7 (m, 31H), 2.22 (broad q, 2H, =CCH2CH3, J = 7 Hz), 4.04 (d a f t e r addition of D 20, 2H, -CH^OH, J = 7 Hz), 6.22 (t of t, IH, v i n y l proton, _J = 6.5, 1.3 Hz, J s n _ H = 128 Hz). Exact Mass calcd. for C 1 3H 2 70Sn (M +-c kH 9): 319.1084; found: 319.1085. Preparation of (E_)-3-(Tri-n-butylstannyl)-2-penten-l-ol (186) This alcohol was prepared via diisobutylaluminum hydride reduc-tion of the ester 184 v i a a procedure i d e n t i c a l with that for the alcohol 185 described above. From 338 mg (0.81 mmol) of 184 there was obtained (air-bath d i s t i l l a t i o n temperature 125-130°C/0.3 Torr) 286 mg n-Bu3Sn - 201 -(94%) of the alcohol 186 as a c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 3270, 1460, 1020 cm"1; *H nmr (80 MHz, CDC1 3) 6: 0.7-1.1 (m, 31H), 2.31 (broad q, 2H, =CCH2CH3, J=7 Hz, 2sn-R = 5 6 Hz>' 4 , 2 5 ( d a f t e r addition of D 20, 2H, -CH20H, J_ = 6 Hz), 5.72 (broad t, IH, v i n y l proton, J = 6 Hz, J S n_H = 70 Hz). Exact Mass calcd. for C 1 3H 270Sn (M+'C^Hg): 319.1084; found: 319.1082. Preparation of (Z)-3-(Tri-n-butylstannyl)-2-pentene (187) n-Bu 3Sn To a cold (0°C), s t i r r e d s olution of the alcohol 185 (2.45 g, 6.52 mmol) in 20 mL of dry THF was added in one portion 1.56 g (9.77 k g mmol) of p y r i d i n e - s u l f u r t r i o x i d e complex . The r e s u l t i n g white suspension was s t i r r e d at 0°C for 3 h. A s o l u t i o n - s l u r r y of l i t h i u m aluminum hydride (1.1 g, 29 mmol) i n 20 mL of dry THF was added and the greenish-grey s l u r r y was s t i r r e d at 0°C for 1 h and at room temperature for 3 h. The mixture was recooled to 0°C and sodium s u l f a t e decahydrate was added i n portions u n t i l noticeable reaction ceased. The r e s u l t i n g white suspension was allowed to warm to room temperature, was treated with anhydrous magnesium s u l f a t e , and then was f i l t e r e d through a short column of F l o r i s i l . The column was washed thoroughly with ether. Removal of the solvent from the combined eluate, followed by d i s t i l l a -- 202 -t i o n (air-bath temperature = 150°C/12 Torr) of the res i d u a l material afforded 2.04 g (87%) of the alkene 18_7_ as a pale yellow o i l . This material exhibited i r ( f i l m ) : 1620, 1460, 1080 cm - 1; XH nmr (80 MHz, CDC1 3) 6: 0.8-1.6 (m, 30H), 1.70 (broad d, 3H, v i n y l methyl protons, J = 6.5 Hz), 2.17 (broad q, 2H, =CCH2CH3, J = 7 Hz, Js n-H = 4 8 H z ) » 6 , 1 0 (t of q, IH, v i n y l proton, J = 1.3, 6.5 Hz, Jgn-H = I 3 8 H z ) » Exact  Mass calcd. for C 1 3H 27Sn (M+'C^Hg): 303.1135; found: 303.1135. Preparation of (E_)-3-(Tri-n-butylstannyl)-2-pentene (188) This alkene was prepared from the a l l y l i c alcohol 186 v i a a procedure i d e n t i c a l with that f o r the preparation of the alkene 187 described above. From 336 mg (0.93 mmol) of 186 there was obtained 278 mg (83%) of 188_ as a pale yellow o i l which exhibited i r ( f i l m ) : 1580, 1440, 1060 cm"1; lR nmr (80 MHz, CDC1 3) 6 : 0.7-1.6 (m, 30H), 1.70 (d, 3H, v i n y l methyl protons, J = 6.6 Hz), 2.27 (broad q, 2H, =CCH?CH3, J = 7.3 Hz, Js n-H = 56 Hz), 5.58 (broad q, IH, v i n y l proton, J_ = 6.6 Hz, J s n _ H = 71 Hz). Exact Mass calcd. for C 1 3 H 2 7 S n (M+H^Hg): 303. 1135; found: 303.1132. n - B u 3 S n - 203 -Preparation of Ethyl 2-Ethylpropenoate (194) C0 2 Et To a cold (-78°C), s t i r r e d s o l u t i o n of lithium diisopropylamide (110 mmol) i n 200 mL of dry THF was added 15.8 g (100 mmol) of ethyl 9 7 o 2-ethylacetoacetate . The bright yellow solution was s t i r r e d at -78 C for 10 min and then was allowed to warm to room temperature. Para-formaldehyde (14 g, 0.47 mol) was added and the r e s u l t i n g suspension was s t i r r e d at room temperature for 1 h and at ref l u x temperature for 4 h. The reaction mixture was cooled to room temperature and excess paraform-aldehyde was removed by f i l t r a t i o n through a short column of F l o r i s i l . The column was thoroughly washed with ether. The solvent was removed from the combined eluate and the residual material was s t i r r e d with saturated aqueous potassium bicarbonate for 1 h. The layers were separated and the aqueous layer was extracted thoroughly with ether. The combined organic extracts were washed successively with 3 M HC1 and brine, and dried over magnesium s u l f a t e . D i s t i l l a t i o n ( a i r - b a t h temperature = 60°C/12 Torr; l i t . 5 3 bp 79-82°C/87 Torr) of the re s i d u a l material obtained on removal of the solvent furnished 5.9 g (46%) of the unsaturated ester 194 as a sweet-smelling l i q u i d . This material exhibited i r ( f i l m ) : 1715, 1620 cm - 1; lE nmr (60 MHz, CDCI3) 6: 1.07 ( t , 3H, -CCH 2CH 3, J = 7 Hz), 1.30 ( t , 3H, -OCH2CH3, J = 7 Hz), 2.30 - 204 -i (broad q, 2H, -CCH2CH3, J = 7 Hz), 4.16 (q, 2H, -0CH2CH3, J = 7 Hz), 5.4-5.5 and 6.0-6.1 (in, ra, IH each, o l e f i n i c protons). Preparation of 2-Ethylpropenoic Acid (319) A mixture of the ester 194 (6.25 g, 49 mmol), aqueous sodium hydroxide (1 M, 65 mL) and ethanol (50 mL) was s t i r r e d together at room temperature for 12 h. The solvent was removed under reduced pressure and the residual material was poured into 75 mL of i c e - c o l d 1 M HC1. The aqueous phase was extracted thoroughly with dichloromethane (5 x 80 mL). The combined extracts were dried over magnesium sulfate and the solvent was removed to afford an o i l which upon d i s t i l l a t i o n ( a i r - b a t h temperature » 100°C/12 Torr; l i t . 9 8 bp 81-83°C/13 Torr) gave 4.20 g (86%) of the unsaturated acid as an acrid-smelling l i q u i d . This material exhibited i r ( f i l m ) : 3500-2400, 1700, 1625, 950 cm - 1; LH nmr (60 MHz, CDCI3) 6: 1.13 ( t , 3H, -CH2CH3, J = 7 Hz), 2.33 (broad q, 2H, -CH 2CH 3, J = 7 Hz), 5.60 and 6.27 (m, IH and broad s, IH, o l e f i n i c protons). - 205 -Preparation of the N,N',N'-Trimethylhydrazide of 2-Ethylpropenoic Acid (191) o A solution of 2-ethylpropenoic acid (4.1 g, 41 mmol) and o x a l y l chloride (11 mL, 126 mmol) i n 180 mL of hexanes was heated (reflux) for 99 1 h . The solvent and excess o x a l y l chloride were removed by d i s t i l l a t i o n (atmospheric presure) and the residue was taken up i n 10 mL of dry dichloromethane. This s o l u t i o n was aded to a cold (-78°C) sol u t i o n of trimethylhydrazine (6.1 g, 82 mmol) and triethylamine (17 55 mL, 123 mmol) i n 150 mL of dichloromethane . The reaction mixture was s t i r r e d at -78°C for 1 h and then was allowed to warm to room temperature. Saturated aqueous ammonium chloride was added and the layers were separated. The organic layer was washed with 1 M hydrochloric acid and dried over anhydrous magnesium s u l f a t e . Removal of the solvent ( d i s t i l l a t i o n at atmospheric pressure), followed by d i s t i l l a t i o n (air-bath temperature 108-112°C/12 Torr) of the residual material, afforded 2.2 g (34%) of the trimethylhydrazide 191. This c o l o r l e s s l i q u i d exhibited i r ( f i l m ) : 1650, 1450, 1380, 905 cm - 1; lR nmr (80 MHz, CDC1 3) 6: 1.05 ( t , 3H, -CH2CH3, J = 7 Hz), 2.31 (broad q, 2H, -CH 2CH 3, J = 7 Hz), 2.47 (s, 6H, -NMe2), 2.88 (s, 3H, -CONMe-), 4.95-5.10 (m, 2H, o l e f i n i c protons). Exact Mass calcd. for C 6Hi6N20: 156.1262; found: 156.1231. - 206 -Preparation of the N,N',N'-Trimethylhydrazide of (Z)-2,4-Diethyl-4-hexenoic Acid (192) To a cold (-20°C), s t i r r e d solution of the vinylstannane 187 (366 mg, 1.02 mmol) in.5 mL of dry THF was added a so l u t i o n of n-butyllithium in hexane (0.6 mL, 1.62 M, 0.97 mmol). The c o l o r l e s s s o l u t i o n was s t i r r e d at -20°C f o r 1 h and then was cooled to -78°C. A so l u t i o n of the trimethylhydrazide 191 (159 mg, 1.02 mmol) in 2 mL of dry THF was added dropwise and the reaction mixture was s t i r r e d at -78°C for 1 h. Saturated aqueous ammonium chloride and ether were added and the layers were separated. The aqueous layer was extracted with ether and the combined extracts were washed with saturated aqueous ammonium chloride and dried over anhydrous magnesium s u l f a t e . Removal of the solvent afforded an o i l which, on the basis of analysis by glc (column A), contained the desired product 192, the two s t a r t i n g materials 187 and 191, and tetra-tv-butyltin. Subjection of t h i s material to column chromatography on s i l i c a gel (25 g, el u t i o n with petroleum ether-ether, 1:1) gave, a f t e r concentration of the appropriate (Rf = 0.40) f r a c t i o n s and d i s t i l l a t i o n (air-bath temperature 109-115°C/12 Torr) of o - 207 -the combined residual material, 97 mg (42%) of the trimethylhydrazide 192. This material exhibited i r ( f i l m ) : 1645, 1460, 1380, 1180, 1155 cm"1; lH nmr (80 MHz, CDC13) 6: 0.82 ( t , 3H, -CH 2CH 3, J = 7 Hz), 0.98 ( t , 3H, -CH 2CH 3, J = 7 Hz), 1.17-2.33 (m, 9H), 2.48 (s, 6H, -NMe2), 2.88 (s, 3H, -CONMe), 3.25-3.73 (m, IH, a-proton), 5.25 (broad q, IH, J = 7 Hz). Exact Mass calcd. for Ci3H 26N 20: 226.2045; found: 226.2046. Preparation of the N,N',N'-Trimethylhydrazide of (E)-2,4-Diethyl-4-hexenoic Acid (193) This compound was prepared from the vinylstannane 188 and the trimethylhydrazide 191 v i a a procedure e s s e n t i a l l y i d e n t i c a l with that for the trimethylhydrazide 192 described above. Column chromatography of the crude material obtained from 900 mg (5.77 mmol) of the trim e t h y l -hydrazide 191 on s i l i c a gel (55 g, e l u t i o n with petroleum ether-ether, 1:1) afforded 534 mg (41%) of the desired product 193. In addition, 341 mg (38%) of the s t a r t i n g trimethylhydrazide 191 was also i s o l a t e d . The desired product exhibited i r ( f i l m ) : 1640, 1450, 1380, 1180, 1150 cm"1; lE nmr (80 MHz, CDC13) 6: 0.82 ( t , 3H, -CH2CH3, J = 7 Hz), 0.98 ( t , 3H, -CH 2CH 3, J = 7 Hz), 1.17-2.35 (m, 9H), 2.46, 2.50, 2.88 (s, s, s, 3H - 208 -each, N-methyl protons), 3.25-3.75 (m, IH, a-proton), 5.20 (broad q, IH, v i n y l proton, J_ = 7 Hz). Exact Mass calcd. for C i 3 H 2 6 N 2 0 : 226.2045; found: 226.2046. Acid Hydrolysis of the Trimethylhydrazide 192: Preparation of 2,4,4-Triethylbutyrolactone (195) o A mixture of the trimethylhydrazide 192 (27.0 mg, 0.13 mmol) and 1 mL of 3 M hydrochloric acid was heated (reflux) for 2 h. The mixture was cooled to room temperature, d i l u t e d with water (5 mL) and thoroughly extracted with dichloromethane ( 3 x 8 mL). The combined organic extracts were washed with water and dried over anhydrous magnesium s u l f a t e . Removal of the solvent, followed by d i s t i l l a t i o n ( a i r - b a t h temperature 100-105°C/12 Torr) of the residual o i l afforded 16.8 mg (78%) of a co l o r l e s s l i q u i d which, on the basis of g l c (column A) an a l y s i s , contained only one component. This material was i d e n t i f i e d as the butyrolactone 195 based on the following: Ir ( f i l m ) : 1770, 1755, 1460 1215, 960 cm - 1; *H nmr (80 MHz, CDC 13) 6: 0.75-1.1 (m, 9H, -CH2CH3), 1.2-1.9 (m, 6H, -CH2CH3), 1.9-2.3 (m, 2H, ring methylene protons), 2.4-2.9 (m, IH, a-proton). Exact Mass calcd. for CIOHI8O2: 170.1307; found: 170.1305. - 209 -Preparation of (Z)-2,4-Diethyl-4-hexenoic Acid (173) o To a cold (-78°C), s t i r r e d solution of the trimethylhydrazide 192 (24 mg, 0.11 mmol) i n 3 mL of dry ether was added a solu t i o n of diisobutylaluminum hydride i n hexane (0.12 mL, 1 M, 0.12 mmol). The reaction mixture was s t i r r e d at -78°C for 30 min and at 0°C for 2 h. Saturated aqueous ammonium chloride (= 0.2 mL) was added and the mixture was allowed to warm to room temperature. The r e s u l t i n g white s l u r r y was treated with anhydrous magnesium sulfate and f i l t e r e d through a short column of F l o r i s i l . The column was washed with ether and the solvent was removed from the combined eluate. The residual material was taken 5 8 up i n dimethylformamide (2 mL); pyridiniura dichromate (200 mg) was added and the mixture was s t i r r e d overnight at room temperature. Water (10 mL) was added and the resultant mixture was extracted thoroughly with ether. The combined extract was washed successively with brine and 2 x 15 mL of 0.1 M aqueous sodium hydroxide (these extracts were retained, see below), and then was dried over magnesium s u l f a t e . Removal of the solvent, followed by bulb-to-bulb d i s t i l l a t i o n of the residual o i l gave 12 mg of the s t a r t i n g material 192. The above-mentioned basic extracts were a c i d i f i e d (1 mL of 3 M hydrochloric acid) and the r e s u l t i n g mixture was extracted with - 210 -dichloromethane (3 x 15 mL). The combined organic s o l u t i o n was dried over anhydrous magnesium s u l f a t e . Removal of the solvent, followed by d i s t i l l a t i o n (air-bath temperature = 100°C/12 Torr) of the re s i d u a l o i l afforded 4.5 mg (50% based on unrecovered 192) of the acid 173 as a c o l o r l e s s l i q u i d . This material exhibited i r ( f i l m ) : 3300-2550, 1700 cm"1; :H nmr (400 MHz, CDC13) 6: 0.99 ( t , 3H, H 8 or H 1 0, J = 7 Hz), 1.02 ( t , 3H, H 8 or H 1 0, J = 7 Hz), 1.55-1.79 and 1.66 (m, 2H, H 9 and d, 3H, H 6, J = 6 Hz), 2.09 (q, 2H, H 7, J = 7 Hz), 2.28-2.40 and 2.49-2.63 (m, IH and m, 2H, H 2 and H 3), 5.05 (q, IH, H 5, J = 6 Hz). Exact Mass calcd. for C10H18O2: 170.1307; found: 170.1309. Preparation of (E)-2,4-Diethyl-4-hexenoic Acid (174) This compound was prepared from the trimethylhydrazide 193 v i a a procedure i d e n t i c a l with that for the acid 173 described above. From 516 mg of 193 there was obtained, i n addition to 180 mg of the s t a r t i n g material 193, 177 mg (70% based on unrecovered 193) of the desired acid 174. This c o l o r l e s s l i q u i d exhibited i r ( f i l m ) : 3400-2400, 1700 cm - 1; XH nmr (400 MHz, CDCI3) 6: 0.95 ( t , 3H, H 8 or H 1 0, J = 7 Hz), 0.97 ( t , 3H, H 8 or H 1 0, J = 7 Hz), 1.51-1.65 and 1.58 (m, 2H, H 9 and d, 3H, H 6, J o 10 8 - 211 -= 6.5 Hz), 2.04 (q, 2H, H 7, J = 7 Hz), 2.15 (d of d, IH, H 3, J = 14, 6 Hz), 2.35 (d of d, IH, H3, J = 14, 8 Hz), 2.42-2.52 (m, IH, H 2 ) , 5.24 (q, IH, H 5, J_ = 6.5 Hz). Exact Mass calcd. for C 1 0H 1 8O 2: 170. 1307; found: 170.1308. VI. Reaction of N,N-Dimethyl-2-alkynamldes with (TrimethylstannyD- copper Reagents A. Preparation of N,W-Dimethyl-2-alkynamldes General Procedure H: Preparation of N,N-Dimethyl-2-alkynamides (197) R-C5C -C0NMe 2 To a cold (-78°C), s t i r r e d solution of the appropriate 1-alkyne (47) in dry THF was added a solution of methyllithium (1 equiv.) i n ether. The reaction mixture was s t i r r e d at -78°C for 30 min and at -20°C for 30 rain. N,N-Dimethylcarbamoyl chloride (= 1.1 equiv.) was introduced and the resultant solution was s t i r r e d at -20°C for 30 min and at room temperature for 2 h. Saturated aqueous sodium bicarbonate was added and the quenched reaction mixture was s t i r r e d at room tempera-ture for 2 h to destroy exces N,N-diraethylcarbamoyl chloride. Ether was added and the layers were separated. The aqueous layer was thoroughly extracted with ether. The combined organic solution was washed with - 212 -saturated aqueous sodium bicarbonate and dried over anhydrous magnesium su l f a t e . Removal of the solvent, followed by d i s t i l l a t i o n of the re s i d u a l o i l provided the corresponding N,N-dimethyl-2-alkynaraide (197). Preparation of N,N-Dimethyl-2-butynaraide (200) M e - C 5 C - C 0 N M e 2 To a cold (-78°C), s t i r r e d solution of propyne (= 2 g, = 50 mmol) i n dry THF (100 mL) was added a solution of methyllithiura (50 mL, 1.00 M, 50 mmol) in ether. The reaction mixture was s t i r r e d at -78°C for 30 min and at -20°C for 30 min. N,N-Dimethylcarbamoyl chloride (5.06 mL, 55 mmol) was added and the reaction mixture was s t i r r e d at -20°C for 30 min and at room temperature for 2 h. Addition of saturated aqueous sodium bicarbonate, followed by normal workup (general procedure H) afforded, a f t e r removal of the solvent, a pale yellow l i q u i d . D i s t i l l a -tion (air-bath temperature * 100°C/20 Torr; l i t . 1 0 0 bp 98-102°C/17-18 Torr) of th i s material provided 4.51 g (81%) of the desired amide as a co l o r l e s s o i l . This material showed i r ( f i l m ) : 2240, 2210, 1630, 1400 cm - 1; XH nmr (80 MHz, CDC1 3) 6: 2.02 (s, 3H, -CCH 3), 2.98 and 3.22 (s, s, 3H each, -NMe2). - 213 -Preparation of N,N-Dimethyl-2-pentynamide (201) E t - C s C - C 0 N M e 2 To a cold (-78°C), s t i r r e d s o l u t i o n of 1-butyne (= 2.7 g, = 50 mmol) i n 150 mL of dry THF was added a solution of methyllithium (50 mL, 1.00 M, 50 mmol) in ether. The co l o r l e s s solution was s t i r r e d at -78°C for 30 min and at 0°C for 1 h. N,N-Diraethylcarbamoyl chloride (5.06 mL, 55 mmol) was added and the r e s u l t i n g dark yellow solution was s t i r r e d at 0°C for 1 h and at room temperature for 2 h. Saturated aqueous sodium bicarbonate (10 mL) was added and the mixture was s t i r r e d at room temperature for 2 h. Normal workup (as outlined i n general procedure H), followed by f r a c t i o n a l d i s t i l l a t i o n (bp 125-130°C/12 Torr) of the crude o i l afforded 5.32 g (85%) of the desired amide (201) as a col o r l e s s l i q u i d . This material was homogeneous by glc (column A) and t i c (developing solvent: petroleum ether-ether, 1:2) analyses and exhibited i r ( f i l m ) : 2230, 2200, 1630, 1400, 1190 cm - 1; *H nmr (100 MHz, CDC1 3) 6: 1.06 ( t , 3H, -CH 2CH 3, J = 7.5 Hz), 2.23 (q, 2H, -CH 2CH 3, J = 7.5 Hz), 2.82 and 3.06 (s, s, 3H each, -NMe2). Exact Mass calcd. for C 7H uN0: 125.0841; found: 125.0843. Preparation of N,N-Dimethyl-5-(2-cyclopentenyl)-2-pentynamide (202) - 214 -Following general procedure H outlined above, a solution of the terminal acetylene 56_ (1.89 g, 15.8 mmol) in dry THF (100 mL) was allowed to react with methyl lithium (15.0 mmol) at -78°C for 30 min and at -20°C f o r 30 rain. The r e s u l t i n g c o l o r l e s s solution was treated with N,N-dimethylcarbamoyl chloride (1.38 mL, 15.0 mmol) and the pale yellow solution was s t i r r e d at -20°C for 30 min and at room temperature for 2 h. Normal workup, followed by removal of the solvent gave a pale yellow o i l . Glc (column A) analysis of t h i s material showed that i t contained a small amount (= 5%) of the s t a r t i n g acetylene _56_ and one other component. Subjection of t h i s material to f l a s h chromatography on s i l i c a gel (4 x 15 cm column, e l u t i o n with petroleum ether-ether, 1:1) afforded, after concentration of the appropriate (Rf = 0.26) fr a c t i o n s and d i s t i l l a t i o n (air-bath temperature 125-130°C/0.2 Torr) of the combined residual material, 2.20 g (77%) of the amide 202 as a c o l o r l e s s l i q u i d . This material exhibited i r ( f i l m ) : 3030, 2230, 2200, 1630 cm"1; Xn nmr (80 MHz, CDC1 3) 6: 1.2-2.2 (m, 4H), 2.2-2.5 and 2.40 (m, 2H, r i n g a l l y l i c methylene protons and t, 2H, y-protons, _J = 7 Hz), 2.6-3.0 (m, IH, ring a l l y l i c methine proton), 2.99 and 3.22 (s, s, 3H each, -NMe2 ) , 5.5-5.9 (m, 2H, o l e f i n i c protons). Exact Mass calcd. for C12H17NO: 191.1310; found: 191.1308. Preparation of 5-_t-Butyldimethylsiloxy-l-pentyne (198) - ) -S iO-(CH 2 ) 3 -CSC-H - 215 -A mixture of 4-pentyn-l-ol (1.68 g, 20 mmol), t - b u t y l -dimethylchlorosilane (3.62 g, 24 mmol), and imidazole (3.40 g, 50 mmol) i n dry dimethylforraamide (12 mL) was s t i r r e d at room temperature for 12 8 6 h . Saturated aqueous sodium bicarbonate (20 mL) was added and the r e s u l t i n g mixture was thoroughly extracted with ether (4 x 25 mL). The combined organic extract was washed with water (4 x 10 mL) and dried over anhydrous magnesium s u l f a t e . Removal of the solvent, followed by f r a c t i o n a l d i s t i l l a t i o n of the crude o i l to remove t^butyldimethyl-s i l a n o l (air-bath temperature <60°C/12 Torr) and d i s t i l l a t i o n (air-bath temperature 75-80°C/12 Torr; l i t . 1 0 2 bp 65°C/9 Torr) of the residual material provided 3.85 g (97%) of the s i l y l ether 198 as a c o l o r l e s s l i q u i d . This material exhibited i r ( f i l m ) : 3300, 2105, 1260, 1110 cm - 1; lE nmr (80 MHz, CDC13) 6: 0.05 (s, 6H, -SiMe 2), 0.90 (s, 9H, -SiCMe3), 1.52-1.83 (m, 2H, -CH 2CH 2CH 2-), 1.91 ( t , IH, -CECH, J_ = 1.3 Hz), 2.27 (d of t, 2H, -C=C-CH2-, J = 1.3, 7 Hz), 3.70 ( t , 2H, -0CH2-, J = 6 Hz). Exact Mass calcd. for CnH220Si: 198.1440; found: 198.1485. Preparation of N,N-Dimethyl-6-jt-butyldimethylsiloxy-2-hexynamide (203) V I - ) - S i 0 - ( C H 2 )3 - C s C - C 0 N M e 2 This material was prepared essentialy as outlined i n general procedure H. Thus, the acetylene 198 (1.88 g, 9.5 mmol) i n dry THF (25 mL) was treated successively with methyllithium (7.69 mL, 1.30 M, 10.0 - 216 -mmol) and N,N-dimethylcarbamoyl chloride (1.01 mL, 11 mmol) under the appropriate conditions. Normal workup, followed by removal of the solvent, gave a pale yellow l i q u i d which contained, on the basis of glc (column A) analysis, a small amount (1%) of s t a r t i n g acetylene 198 and the desired amide. Low-boiling material was removed by d i s t i l l a t i o n ( a ir-bath temperature <80°C/1 Torr) and the res i d u a l material was d i s t i l l e d (air-bath temperature 140-145°C/0.8 Torr) to afford 2.34 g (92%) of the amide 203 as a c o l o r l e s s o i l . This material consisted of one component by glc (column A) analysis and exhibited i r ( f i l m ) : 2210, 1630, 1390, 1110, 840 cm - 1; *H nmr (80 MHz, CDC1 3) 6: 0.02 (s, 6H, -SiMe 2), 0.86 (s, 9H, -SiCMe 3), 1.77 (m, 2H, -CH 2CH 2CH 2-), 2.45 ( t , 2H, -C=C-CH2-, J = 7 Hz), 2.97, 3.19 (s, s, 3H each, -NMe2), 3.70 ( t , 2H, -0CH2-, J = 6 Hz). Exact Mass calcd. for C 1 3H 2 i +N0 2Si (M +-CH 3): 254.1576; found: 254.1576. Preparation of N,N,4,4-Tetramethyl-2-pentynamide (204) t - B u - C 5 C - C 0 N M e 2 To a cold (-78°C), s t i r r e d s o l u t i o n of 3,3-dimethyl-l-butyne (1.39 g, 17 mmol) i n 100 mL of dry THF was added a solution of methyl-li t h i u m (11.5 mL, 15 mmol) i n ether. The c o l o r l e s s solution was s t i r r e d at -78°C for 30 min and at -20°C for 30 min. N,N-Dimethylcarbamoyl chloride (1.38 mL, 15 mmol) was added and the reaction mixture was - 217 -s t i r r e d at -20°C for 30 min and at room temperature for 2 h. Normal workup (general procedure H), followed by d i s t i l l a t i o n ( air-bath temperature 110-115°C/12 Torr) of the crude residue gave 2.18 g (95%) of the desired amide 204 as white needles (mp 63.0-63.5°C; l i t . 1 0 3 mp 65.0-65.5°C). This material exhibited i r ( C H C 1 3 ) : 2210, 1620, 1400, 1220 cm - 1; XH nmr (60 MHz, CDCI3) 6: 1.31 (s, 9H, -CMe3), 2.94, 3.16 (s, s, 3H each, -NMe2). Exact Mass calcd. for C 9H 1 5N0: 153.1153; found: 153.1154. B. Preparation o f (E)-and (Z)-N,N-Dimethyl-3-trimethylstannyl-2-alkenamide s General Procedure I: Reaction of N,N-Dimethyl-2-alkynamides with  Lithium (Phenylthio)(trimethylstannyl)cuprate i n THF. Preparation of CE)-N,N-Dimethyl-3-(trimethylstannyl)-2-alkenamides (213) Me 3Sn •K R CONMe 2 To a cold (-78°C), s t i r r e d solution of lithium (phenylthio)-(trimethylstannyl)cuprate (14) (0.45 mmol) in 5 mL of dry THF was added a THF solution (0.5 mL) of the appropriate acetylenic amide (0.3 mmol). The dark red reaction mixture was s t i r r e d at -78°C for 3 h. Methanol (= 0.2 mL) and ether (15 mL) were added successively and the mixture was - 218 -allowed to warm to room temperature. The r e s u l t i n g yellow s l u r r y was treated with anhydrous magnesium sulfate and f i l t e r e d through a short column of F l o r i s i l . The column was washed with further volumes of ether. Removal of the solvent from the combined eluate gave an o i l which contained hexamethylditin and the desired amide. The o i l was chromatographed on 3 g of s i l i c a g e l . E l u t i o n with petroleum ether-ether, 100:1 (= 10 mL) removed hexamethylditin; further e l u t i o n with ether afforded, a f t e r removal of the solvent and bulb-to-bulb d i s t i l l a t i o n of the residual o i l , the corresponding pure (E_) trim e t h y l -stannyl amide 213. General Procedure J : Addition of the (Trimethylstannyl)copper Reagent (44) to N,N-Dimethyl-2-alkynamides To a cold (-78°C), s t i r r e d solution of the (trimethylstannyD-copper reagent (44) (0.45 mmol) in 5 mL of dry THF was added a THF sol u t i o n (0.5 mL) of the appropriate acetylenic amide (0.3 mmol). The reaction mixture was s t i r r e d at -78°C for 3 h. Saturated basic aqueous ammonium chloride (1 mL) and ether (15 mL) were added successively and the resultant mixture was allowed to warm to room temperature with vigorous s t i r r i n g . S t i r r i n g was maintained u n t i l the aqueous phase became deep blue; the layers were then separated. The organic layer was washed with saturated ammonium chloride (pH 8) and dried over magnesium s u l f a t e . Removal of the solvent gave an o i l which, on the basis of g l c (column A) analysis, contained hexamethylditin and the corresponding (E) - 219 -trimethylstannyl amide 213. The mixture was chromatographed on 3 g of s i l i c a g e l . E l u t i o n with petroleum ether-ether, 100:1 (= 10 mL) removed hexamethylditin; further e l u t i o n with ether, followed by removal of the solvent and bulb-to-bulb d i s t i l l a t i o n of the residual o i l gave the desired (E_) trimethylstannyl amide 213. General Procedure K: Reaction of N,N-Dimethyl-2-alkynamides with  Lithium (Phenylthio)(trimethylstannyl)cuprate under "Thermodynamic Conditions." Preparation of (Z_)-N,N-Dimethyl-3-trimethylstannyl-2-alkenamides Me,Sn CONMe 2 R To a cold (-48°C), s t i r r e d solution of lithium (phenylthio)-(trimethylstannyl)cuprate (0.45 mmol) i n 2.5 mL of dry THF was added a THF solution (0.5 mL) of the appropriate acetylenic amide (0.3 mmol). The reaction mixture was s t i r r e d at -48°C for 1 h. Dry ether (5 mL) was slowly added and the reaction mixture was s t i r r e d at -48°C for 1 h, at -20°C for 1 h and at 0°C for 2 h. Methanol (= 0.2 mL) and ether (10 mL) were added and the reaction mixture was allowed to warm to room tempera-ture. The bright yellow s l u r r y which formed was treated with anhydrous magnesium sulfate and f i l t e r e d through a short column of F l o r i s i l . The column was washed with further volumes of ether. Removal of the solvent - 220 -from the combined eluate gave an o i l which contained, on the basis of glc (column A) analysis, hexamethylditin and a mixt ure of the expected (E_) and (Z) t i n amides 213 and 214. Subjection of t h i s o i l to column chromatography or f l a s h chromatography on s i l i c a gel afforded, a f t e r removal of the solvent from the appropriate f r a c t i o n s and bulb-to-bulb d i s t i l l a t i o n of the material contained therein, the desired pure (Z) trimethylstannyl amide 214. Preparation of (E_)-N,N-Dimethyl-3-trimethylstannyl-2-butenamide (205) Me 3Sn Me C 0 N M e 2 a) Using lithium (phenylthio)(trimethylstannyl)cuprate (14) Following general procedure I, there was obtained 63.2 mg (76%) of the unsaturated amide 205 (air-bath d i s t i l l a t i o n temperature - 60°C/ 0.2 Torr) as a c o l o r l e s s l i q u i d from 33.3 mg (0.3 mmol) of N,N-diraethyl-2-butynamide (200). The amide 205_ exhibited i r ( f i l m ) : 1630, 1400, 1160, 780 cm - 1; XH nmr (80 MHz, CDC1 3) 6: 0.15 (s, 9H, -SnMe3, Jsn-H = 52/55 Hz), 2.02 (d, 3H, y-protons, J = 2 Hz, J s n - H = 4 8 H z )» 2 , 9 8» 3.00 (s, s, 3H each, -NMe2), 6.07 (q, IH, v i n y l proton, J = 2 Hz, iSn-H = 7 3 H z ) * Exact Mass calcd. for C 8H 1 6N0Sn (M+-CH3): 262.0254; found: 262.0255. - 221 -b) Using the (trimethylstannyl)copper reagent (44) Following general procedure J outlined above, there was obtained 69.1 mg (83%) of the unsaturated amide 205 as a c o l o r l e s s o i l from 33.1 mg (0.3 mmol) of the acetylenic amide 200. The spe c t r a l properties ( i r , *H nmr) of t h i s product were i d e n t i c a l with those reported above. c) Using lithium (cyano)(trimethylstannyl)cuprate (46) To a cold (-48°C), s t i r r e d solution of lithium (cyano)(trimethyl-stannyl) cuprate (46) (0.39 mmol) i n 5 mL of dry THF was added a THF solution (0.5 mL) of the acetylenic amide 200 (32.6 mg, 0.3 mmol). The reaction mixture was s t i r r e d at -48°C for 3 h. Normal workup, as described In general procedure J , followed by d i s t i l l a t i o n ( a i r - b a t h temperature - 90°C/12 Torr) of the chromatographed o i l afforded 75.6 mg (93%) of the desired unsaturated amide 205 as a c o l o r l e s s o i l . The *H nmr spectrum of this material was i d e n t i c a l with that reported above. Preparation of (Z)-N,N-Dimethyl-3-trimethylstannyl-2-butenaraide (208) Me,Sn^ CONMe a Me / y This material was prepared as described i n general procedure K. Thus, reaction of N,N-dimethyl-2-butynamide (33.3 mg, 0.3 mmol) under the reaction conditions s p e c i f i e d followed by normal workup afforded a - 222 -yellow o i l which contained, on the basis of glc (column A) analysis, hexamethylditin and a mixture of the (E) and (Z) butenamides 205 and 208 i n a r a t i o of 5:95, respectively. Subjection of th i s material to column chromatography on s i l i c a gel (8 g, el u t i o n with petroleum ether-ether, 3:1) provided a c o l o r l e s s o i l which upon d i s t i l l a t i o n (air-bath temperature = 60°C/0.2 Torr) gave 57.2 mg (69%) of the (Z) butenaraide 208 as a viscous o i l which slowly c r y s t a l l i z e d to white needles. This material exhibited mp 49-50°C; i r (KBr): 1730, 1630, 1160, 770, 710 cm - 1; i r (CHC1 3): 1625, 1580, 1400, 1165, 850 cm"1; XH nmr (80 MHz, CDCI3) 6: 0.13 (s, 9H, -SnMe3, J s n _ H = 53/55 Hz), 2.15 (d, 3H, Y-protons, J = 2 Hz, J s n - H = 4 8 H z)> 2« 9 8» 3 « 1 0 (s» s> 3 H e a c h> -NMe2), 6.85 (q, IH, v i n y l proton, J = 2 Hz, J s n _ H = 124 Hz). Exact  Mass calcd. for C 8H 1 6NOSn (M +-CH 3): 262.0254; found: 262.0236. Anal, calcd. for C 9H 1 9N0Sn: C 39.17, H 6.94, N 5.08; found: C 39.18, H 6.99, N 5.10. Preparation of (E)-N,N-Dimethyl-3-trimethylstannyl-2-pentenamide (215) Me 3Sn Et C 0 N M e 2 a) Using lithium (phenylthio)(trimethylstannyl)cuprate (14) Following general procedure I outlined above, there was obtained 68.5 mg (81%) of the unsaturated amide 2L5 (air-bath d i s t i l l a t i o n - 223 -temperature 132-136°C/12 Torr) as a c o l o r l e s s o i l from 36.2 mg (0.3 mmol) of the acetylenic amide 201. This product exhibited i r ( f i l m ) : 1620, 1385, 1145, 775 cm - 1; XH nmr (80 MHz, CDC13) 6: 0.17 (s, 9H, -SnMe3, i s n _ H = 52/54 Hz), 1.02 ( t , 3H, -CH 2CH 3, J = 7.5 Hz), 2.45 (broad q, 2H, -CH^CH^ J = 7.5 Hz, J s n _ H = 59 Hz), 2.97, 3.01 (s, s, 3H each, -NMe2), 6.04 (broad s, IH, v i n y l proton, J s n _ H = 75 Hz). Exact Mass calcd. for C 9H 1 8NOSn (M+-CH3): 276.0410; found: 276.0410. b) Using the (trimethylstannyl)copper reagent (44) Following general procedure J outlined above, there was obtained 80.0 mg (91%) of the desired amide 215 from 37.8 mg (0.3 mmol) of the acetylenic amide 201. The spectral properties ( i r , *H nmr) of t h i s product were i d e n t i c a l with those reported above. Preparation of (Z)-N,N-Dimethyl-3-trimethylstannyl-2-pentenamide (216) Following general procedure K outlined above, the acetylenic amide 201 (37.0 mg, 0.3 mmol) was allowed to react with lithium (phenylthio)(trimethylstannyl)cuprate under the stated conditions. Normal workup afforded a yellow o i l which contained, on the basis of glc (column A) analysis, hexamethylditin and a mixture of the (E) and (Z) Me 3Sn CONMe 2 - 224 -pentenamides 215 and 216 i n a r a t i o of 4:96, res p e c t i v e l y . Subjection of t h i s o i l to column chromatography on s i l i c a gel (8 g, e l u t i o n with petroleum ether-ether, 3:1) afforded an o i l which upon d i s t i l l a t i o n ( air-bath temperature - 130°C/12 Torr) gave 63.0 mg (73%) of the (Z) pentenamide 216 as a c o l o r l e s s l i q u i d . This material exhibited i r ( f i l m ) : 1625, 1580, 1410, 1400, 1165, 775 cm - 1; *H nmr (100 MHz, CDC1 3) 6: 0.10 (s, 9H, -SnMe3, Jgn-H = 5 4 H z ) . l - 0 2 ( t , 3 H » -CH 2CH 3, J = 7.5 Hz), 2.44 (broad q, 2H, -CH 2CH 3, J = 7.5 Hz), 2.98, 3.10 (s, s, 3H each, -NMe 2) > 6.79 (broad s, IH, v i n y l proton, Jj5n-H = 128 Hz). Exact Mass calcd. for C 9H 1 8N0Sn (M +-CH 3): 276.0410; found: 276.0395. Preparation of (E_)-N,N-Dimethyl-6-_t-butyldiraethylsiloxy-3-trimethyl-stannyl-2-hexenamide (217) a) Using lithium (phenylthio)(trimethylstannyl)cuprate (14) Following general procedure I outlined above, there was obtained, from 80.1 mg (0.3 mmol) of the acetylenic amide 203, a col o r l e s s o i l which upon d i s t i l l a t i o n ( air-bath temperature 120-125°C/ 0.2 Torr) gave 98.6 mg (76%) of the unsaturated amide 217 as a c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 1630, 1390, 1260, 1100, 840, Me 3Sn - 225 -780 cm - 1; XH nmr (80 MHz, CDC1 3) 6: 0.05 (s, 6H, -SiMe 2), 0.21 (s, 9H, -SnMe3, J s n _ R = 52/54 Hz), 0.93 (s, 9H, -SiCMe 3), 1.4-1.8 (m, 2H, -CH 2CH 2CH 2-), 2.4-2.6 (m, 2H, y-protons), 2.92, 3.00 (s, s, 3H each, -NMe 2) > 3.35 ( t , 2H, -OCH2-, J = 6 Hz), 6.08 (broad s, IH, o l e f i n i c 420.1381; found: 420.1355. b) Using the (trimethylstannyl)copper reagent (44) Following general procedure J outlined above, there was obtained 101 mg (78%) of the unsaturated amide 217 from 80.5 mg (0.3 mmol) of the acetylenic amide 203. The *H nmr spectrum of th i s product was i d e n t i c a l with that reported above. Preparation of (Z)-N,N-Dimethyl-6-t-butyldimethylsiloxy-3-trimethylstannyl-2-hexenamide (218) This material was prepared according to general procedure K. From 80.4 rag (0.3 mmol) of the acetylenic amide 203 there was obtained a co l o r l e s s o i l which contained, on the basis of glc (column A) analysis, hexamethylditin and a mixture of the (E) and (Z) hexenamides 217 and 218 i n a r a t i o of 5:95, re s p e c t i v e l y . Subjection of t h i s material to f l a s h proton, Js n-H = 7 4 R z ) . Exact Mass calcd. for C 1 6H 3 1 +N0 2SiSn (M +-CH 3): Me 3Sn CONMe 2 - 226 -chromatography on s i l i c a gel (2 x 15 cm column, e l u t i o n with petroleum ether-ether, 5:1) afforded a c o l o r l e s s o i l which upon d i s t i l l a t i o n ( a i r - b a t h temperature 90-95°C/0.2 Torr) furnished 99.5 mg (76%) of the (Z) hexenamide 218 as a c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 1625, 1580, 1400, 1260, 1110, 840, 780 era" 1; XH nmr (80 MHz, CDC1 3) 6: 0.06 (s, 6H, -SiMe2), 0.13 (s, 9H, -SnMe3, Jj3n-H = 53/55 Hz), 0.92 (s, 9H, -SiCMe 3), 1.4-1.8 (m, 2H, -CH 2CTl 2CH 2-) , 2 « 5 1 (broad t, 2H, y-protons, J = 7.5 Hz), 3.00, 3.11 (s, s, 3H each, -NMe2)> 3.60 ( t , 2H, -0CH2-, J = 6 Hz), 6.81 (broad s, IH, o l e f i n i c proton, Js n-H = 1 2 6 Hz). Exact Mass calcd. for Ci6H3i+N02SiSn (M+'CHg): 420.1381; found: 420.1387. Preparation of (E_)-N,N-Dimethyl-5-(2-cyclopentenyl)-3-trimethylstannyl-2-pentenamide (219) a) Using lithium (phenylthio)(triraethylstannyl)cuprate (14) Following general procedure I outlined above, there was obtained 81.8 mg (77%) of the unsaturated amide 219 as a c o l o r l e s s o i l from 56.9 mg (0.3 mmol) of the acetylenic amide 202. This product exhibited i r ( f i l m ) : 1630, 1380, 1140, 770, 720 cm - 1; *H nmr (400 MHz, CDCI3) 6: Me 3Sn - 227 -0.19 (s, 9H, -SnMe3, Js n_ H = 54 Hz), 1.30-1.53 (m, 3H), 1.99-2.08 (m, IH), 2.21-2.38 (m, 2H, r i n g a l l y l i c methylene protons), 2.50 ( t , 2H, y-protons, J = 8 Hz, Js n-H = 6 0 H z ) > 2.59-2.68 (m, IH, methine proton), 2.98, 3.01 (s, s, 3H each, -NMe2), 5.62-5.67 and 5.69-5.74 (m, m, IH each, ri n g o l e f i n i c protons), 6.07 (broad s, IH, a-proton, Jg n-H = 76 Hz). Exact Mass calcd. for C1i+H2i+N0Sn (M +-CH 3): 342.0880; found: 342.0880. b) Using the (trimethylstannyl)copper reagent (44) Following general procedure J outlined above, there was obtained 80.3 mg (80%) of the unsaturated amide 219 from 53.6 mg (0.3 mmol) of the acetylenic amide 202. The H^ nmr spectrum of this product was i d e n t i c a l with that reported above. Preparation of (Z_)-N,N-Diraethyl-5-(2-cyclopentenyl)-3-triraethylstannyl-2-pentenamide (220) Following general procedure K outlined above, the acetylenic amide 202 (57.0 mg, 0.3 mmol) was allowed to react with lithium (phenyl-thio) (trimethylstannyl) cuprate (0.45 mmol) under the conditions s p e c i -- 228 -f l e d . Normal workup gave a c o l o r l e s s o i l which contained, on the basis of g lc (column A) analysis, hexamethylditin and a mixture of the expected (E) and (Z) unsaturated amides 219 and 220 i n a r a t i o of 7:93, respectively. Subjection of th i s material to f l a s h chromatography on s i l i c a gel (2 x 15 cm column, e l u t i o n with petroleum ether-ether, 5:1) afforded an o i l which upon d i s t i l l a t i o n ( a i r - b a t h temperature -130°C/0.2 Torr) furnished 76.9 mg (72%) of the (Z) pentenamide 220_ as a col o r l e s s o i l . This material exhibited i r ( f i l m ) : 1625, 1575, 1410, 1390, 1160, 770 cm"1; XH nmr (400 MHz, CDC1 3) 6 : 0.13 (s, 9H, -SnMe3, J^n-H = 54/56 Hz), 1.31-1.52 (m, 3H), 2.00-2.09 (m, IH), 2.21-2.41 (m, 2H, r i n g a l l y l i c methylene protons), 2.43-2.50 (m, 2H, y-protons, £Sn-H = 5 0 H z ) » 2.60-2.71 (m, IH, methine proton), 2.98, 3.10 (s, s, 3H each, -NMe2), 5.65-5.76 (m, 2H, ring o l e f i n i c protons), 6.79 (s, IH, a-proton, Js n_H = 1 2 6 H z ) * Exact Mass calcd. for C 1 1 +H 2 i +N0Sn (M^-c^): 342.0880; found: 342.0879. Preparation of (E )-N,N,4,4-Tetramethyl-3-trimethylstannyl-2-pentenamide (221) To a cold (-48°C), s t i r r e d solution of the cuprate reagent _14_ (0.9 mmol) i n 5 mL of dry THF was added a solution of the acetylenic - 229 -amide 204 (45.5 mg, 0.3 mmol) i n 0.5 mL of dry THF. The dark red reaction mixture was s t i r r e d at -48°C for 12 h. Normal workup, as outlined i n general procedure I, afforded a c o l o r l e s s o i l which contained, on the basis of glc (column A) analysis, hexamethylditin and a mixture of the (E_) and (Z) pentenamides 221 and 222 i n a r a t i o of 88:12, respectively. Subjection of this material to f l a s h chromato-graphy on s i l i c a gel (17 g, e l u t i o n wth petroleum ether-ether, 3:1), followed by concentration of the appropriate frac t i o n s and d i s t i l l a t i o n ( a i r - b a t h temperature 86-95°C/0.3 Torr) of the res i d u a l material afforded 65.2 mg (69%) of the (E) pentenamide 221. This c o l o r l e s s o i l exhibited i r ( f i l m ) : 1625, 1400, 780 cm - 1; XH nmr (80 MHz, CDC 13) 6: 0.22 (s, 9H, -SnMe3, J s n _ H = 52 Hz), 1.16 (s, 9H, -CMe 3), 2.96, 3.02 (s, s, 3H each, -NMe2), 5.87 (s, lH, o l e f i n i c proton, J s n - H = 9 0 H z )« Exact Mass calcd. for C 1 1H 2 2N0Sn (M +-CH 3): 304.0723; found: 304.0720. Preparation of (Z)-N,N,4,4-Tetramethyl-3-triraethylstannyl-2-pentenamide To a cold (-48°C), s t i r r e d solution of the cuprate reagent ]A_ (0.9 mmol) i n 4 mL of anhydrous tetrahydrofuran was added the acetylenic amide 204 (45.0 mg, 0.3 mmol) as a solution i n 0.5 mL of dry THF. The (222) Me,Sn CONMe 2 - 230 -reaction mixture was s t i r r e d at -48°C for 6 h. Dry ether (10 mL) was slowly added and the r e s u l t i n g mixture was s t i r r e d at -48°C for 1 h, at -20°C for 1 h, and at 0°C for 3 h. Normal workup (general procedure K) afforded an o i l which contained, on the basis of glc (column A) an a l y s i s , hexamethylditin and a mixture of the (E) and (Z) pentenaraides 221 and 222 in a r a t i o of 5:95, re s p e c t i v e l y . Subjection of t h i s material to f l a s h chromatography on s i l i c a gel (17 g, e l u t i o n with petroleum ether-ether, 5:1) followed by concentration of the appropriate (R f = 0.35) fr a c t i o n s and d i s t i l l a t i o n ( a ir-bath temperature 80-90°C/ 0.3 Torr) of the residual material gave 67.7 mg (72%) of the (Z) pentenamide 222. This c o l o r l e s s o i l exhibited i r ( f i l m ) : 1625, 1570, 1400, 1160, 870, 780 cm - 1; XH nmr (80 MHz, CDC 13) 6: 0.19 (s, 9H, -SnMe3, Jsn-H = 5 4 H z > » 1 « 1 7 (s» 9H, -CMe 3), 2.98, 3.10 (s, s, 3H each, -NMe2), 6.74 (s, IH, o l e f i n i c proton, Jgn-H = 130/136 Hz). Exact Mass calcd. for C 1 1H 2 2N0Sn (M +-CH 3): 304.0723; found: 304.0721. C. Trapping of the Intermediate with Electrophiles other than Proton General Procedure L: Reaction of the Intermediate formed by the  Addition of Lithium (Cyano)(trimethylstannyl)cuprate to N,N-Dimethyl- 2-butynamide with E l e c t r o p h i l e s To a cold (-48°C), s t i r r e d solution of lithium (cyano)(trimethyl-stannyl) cuprate (46) (0.39 mmol) i n 5 mL of dry THF was added a THF s o l u t i on (0.5 mL) of N,N—dimethyl—2—butynamide (0.3 mmol). The r e s u l t i n g bright yellow solution was s t i r r e d at -48°C for 3 h. - 231 -Hexamethylphosphoraraide (HMPA) (0.5 mL) and the appropriate e l e c t r o p h i l e (0.5 mmol) were added and the reaction mixture was s t i r r e d at -48°C for 2 h, then allowed to warm slowly to room temperature and s t i r r e d at that temperature for 12 h. Saturated basic aqueous ammonium chloride (5 mL) and ether (15 mL) were added to the co l o r l e s s s o l u t i o n and the r e s u l t i n g mixture was vigorously s t i r r e d u n t i l the aqueous phase became deep blue. The layers were separated. The organic layer was washed succes-s i v e l y with saturated basic aqueous ammonium chloride (3 mL), saturated aqueous copper sulfate ( 3 x 3 mL) and saturated basic aqueous ammonium chloride (3 mL), and dried over anhydrous magnesium s u l f a t e . Removal of the solvent gave an o i l which contained, on the basis of glc (column A) analysis, hexamethylditin, the desired product, and a small amount (= 3%) of (E)-N,N-dimethyl-3-trimethylstannyl-2-butenamide (205). Subjec-tion of this o i l to column chromatography on s i l i c a gel (8 g, e l u t i o n with petroleum ether-ether, 1:1), followed by bulb-to-bulb d i s t i l l a t i o n of the appropriate material afforded the desired p u r i f i e d product. General Procedure M: Reaction of the Intermediate formed by the Addition of the (Trimethylstannyl)copper Reagent (44) to a,8-Acetylenic Amides with E l e c t r o p h i l e s To a cold (-78°C), s t i r r e d solution of the (t r i m e t h y l s t a n n y l ) -copper reagent (44) (0.45 mmol) i n 5 mL of anhydrous THF was added a THF solution (0.5 mL) of the appropriate a,8-acetylenic amide (0.3 mmol). The dark red reaction mixture was s t i r r e d at -78°C for 3 h. Dry - 232 -hexamethylphosphoraraide (HMPA) (0.5 mL) and the appropriate e l e c t r o p h i l e (0.5 mmol) were added and the reaction mixture was s t i r r e d at -78°C for 3 h, then allowed to slowly warm to room temperature and s t i r r e d at that temperature for 12 h. Normal workup of the c l e a r - b l u i s h reaction mixture, as outlined i n general procedure L, gave a crude yellow o i l which contained, on the basis of glc (column A) analysis, hexamethyl-d i t i n , the desired product, and a minute amount (<1%), or none of the protonated (E_) alkenamide 213. Subjection of this o i l to column chroma-tography on s i l i c a gel (8 g, e l u t i o n with petroleum ether-ether, 1:1), followed by bulb-to-bulb d i s t i l l a t i o n of the material contained i n the appropriate f r a c t i o n s , afforded the desired p u r i f i e d product. Preparation of (E)-N,N,2-Trimethyl-3-trimethylstannyl-2-butenamide (225) a) Using lithium (cyano)(trimethylstannyl)cuprate (46) Following general procedure L outlined above, the ace t y l e n i c amide 200 (32.4 mg, 0.3 mmol) was allowed to react with the cuprate reagent 46_ (0.39 mmol) and iodomethane (31 uL, 0.5 mmol) under the conditions s p e c i f i e d . Subjection of the crude o i l obtained upon normal workup of the reaction mixture to column chromatography on s i l i c a gel (8 g, e l u t i o n with petroleum ether-ether, 1:1), followed by concentration Me,Sn Me Me X C 0 N M e 2 - 233 -of the appropriate (Rf = 0.19) fr a c t i o n s and d i s t i l l a t i o n (air-bath temperature 120-125°C/12 Torr) of the combined re s i d u a l material furnished 71.5 mg (84%) of the desired methylated product 225 as a co l o r l e s s o i l . This material exhibited i r ( f i l m ) : 1610, 1385, 770 cm - 1; XH nmr (80 MHz, CDC1 3) 6: 0.20 (s, 9H, -SnMe 3, Jsn-H = 52/54 Hz), 1.78 (q, 3H, y p r o t o n s , J = 1.5 Hz, J s n _ H = 49 Hz), 1.92 (q, 3H, a-methyl protons, J = 1.5 Hz), 2.95, 2.98 (s, s, 3H each, -NMe2). Exact  Mass calcd. for C 9H 1 8NOSn (M +-CH 3): 276.0411; found: 276.0413. b) Using the (trimethylstannyl)copper reagent (44) Following general procedure M outlined above, N,N-dimethyl-2-butynamide (30.0 mg, 0.3 mmol) was reacted with the (trimethylstannyD-copper reagent (0.45 mmol) followed by iodoraethane (31 uL, 0.5 mmol) under the conditions s p e c i f i e d . Normal workup, followed by chromato-graphy and d i s t i l l a t i o n as i n (a) above provided 68.6 mg (87%) of the desired product 225 as a co l o r l e s s o i l . The H^ nmr spectrum of th i s material was i d e n t i c a l with that reported above. Preparation of (E_)-N,N-Dimethyl-2-(2-propenyl)-3-trimethylstannyl-2-butenamide (226) h c Me 3Sn h, IB Me C0NMe 2 - 234 -a) Using lithium (cyano)(trimethylstannyl)cuprate (46) Following general procedure L outlined above, N,N-dimethyl-2-butynamide (200) (30.7 mg, 0.3 mmol) was allowed to react with lithium (cyano)(trimethylstannyl)cuprate (46) (0.39 mmol) followed by 3-bromo-propene (43 uL, 0.5 mmol) under the conditions s p e c i f i e d . Normal workup, followed by column chromatography of the crude o i l gave a c o l o r l e s s o i l which upon d i s t i l l a t i o n ( a ir-bath temperature - 125°C/12 Torr) furnished 66.6 mg (76%) of the unsaturated amide 226. This material exhibited i r ( f i l m ) : 1625, 1390, 780 cm - 1; lH nmr (400 MHz, CDC1 3) 6: 0.21 (s, 9H, -SnMe3, J s n _ H = 52/54 Hz), 1.79 ( t , 3H, y-protons, J. = 1 H z » iSn-H = 4 7 / 4 9 H z ) > 2.85, 3.19 (broad s, broad s, IH each, H A), 2.92, 2.97 (s, s, 3H each, -NMe2), 4.99 (broad d of d, 1 H» HB» iBC = 2 H z . isD = 1 0 H z ) ' 5 , 0 6 ( d o f d o f c ' 1 H » HC» ^CD = * 7 Hz» i c ~ ^ H z » ^AD = 7 H z ) « Exact Mass calcd. for C nH 2oNOSn (M +-CH 3): 302.0567; found: 302.0569. b) Using the (trimethylstannyl)copper reagent (44) This reaction was performed as described in general procedure M. From 32.6 mg (0.3 mmol) of N,N-dimethyl-2-butynamide (200) and 44 |iL, (0.5 mmol) of 3-broraopropene there was obtained 76.5 mg (82%) of the desired unsaturated amide 226 as a c o l o r l e s s o i l . The chromatographic (glc and t i c ) and spectral ('^H nmr) properties of t h i s material were i d e n t i c a l with those of the material prepared in (a) above. - 235 -Preparation of (E_)-N,N-Dimethyl-2-(2-methyl-2-propenyl)-3-trimethyl-stannyl-2-butenamide (227) a) Using lithium (cyano)(trimethylstannyl)cuprate (46) This reaction was performed as outlined i n general procedure L. From 32.9 mg (0.3 mmol) of N,N-dimethyl-2-butynamide (200) and 57 \iL (0.5 mmol) of 3-iodo-2-raethylpropene 6 1 there was obtained 79.5 mg (81%) of the unsaturated amide 227 (air-bath d i s t i l l a t i o n temperature 130-135°C/12 Torr) as a c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 1620, 1390, 775 cm - 1; XH nmr (80 MHz, CDC1 3) 6: 0.24 (s, 9H, -SnMe3, Jj3n-H = 52/54 Hz), 1.74 (broad s, 3H, v i n y l methyl protons), 1.83 (br s, 3H, y-protons, J s n _ H = 49 Hz), 2.93, 2.96 and 2.95 (s, s, 3H each, -NMe2 and broad s, 2H, a l l y l i c methylene protons), 4.78 (broad s, 2H, v i n y l protons). Exact Mass calcd. for Ci 2H 2 2NOSn (M +-CH 3): 316.0724; found: 316.0721. b) Using the (trimethylstannyl)copper reagent (44) ' This reaction was performed as outlined i n general procedure M. From 32.9 mg (0.3 mmol) of N,N-diraethyl-2-butynaraide (200) and 57 uL (0.5 mmol) of 3-iodo-2-methylpropene there was obtained 73.6 mg (78%) of the unsaturated amide 227 as a c o l o r l e s s o i l . This material was i d e n t i -cal ( g l c , t i c , *H nmr) with the material prepared i n (a) above. Me C O N M e 2 - 236 -Preparation of (E_)-N,N-Dimethyl-2-(3-methyl-2-butenyl)-3-trimethyl-stannyl-2-butenamide (228) a) Using lithium (cyano)(trimethylstannyl)cuprate (46) Following general procedure L outlined above, N,N-dimethyl-2-butynamide (32.7 mg, 0.3 mmol) was allowed to react with l i t h i u m (cyano)(trimethylstannyl)cuprate (0.39 mmol) and l-bromo-3-raethyl-2-butene (58 uL, 0.5 mmol) under the conditions s p e c i f i e d . Subjection of the yellow o i l obtained v i a normal workup to f l a s h chromatography on s i l i c a gel (2 x 15 cm column, e l u t i o n with petroleum ether-ether, 2:1) gave a colo r l e s s o i l which upon d i s t i l l a t i o n ( a i r - b a t h temperature 132-135°C/12 Torr) provided 77.3 mg (76%) of the unsaturated amide 228. This o i l exhibited i r ( f i l m ) : 1625, 1390, 780 cm"1; XH nmr (400 MHz, CDC1 3) 6: 0.22 (s, 9H, -SnMe3, i s n-H = 5 2 / 5 4 H z ) » 1 , 5 9 » 1 , 6 8 ( s> s ' 3 H each, gem-vinyl methyl protons), 1.78 (s, 3H, Y - P r o C o n s , ^Sn-H = 4 9 Hz), 2.75, 3.21 (broad s, broad s, IH each, a l l y l i c methylene protons), 2.91, 2.96 (s, s, 3H each, -NMe2), 5.08 ( t , IH, v i n y l proton, J = 7 Hz). Exact Mass calcd. for C 1 3H 2 1 +NOSn (M+-CH3): 330.0880; found: 330.0879. Me CONMe 2 - 237 -b) Using the (trimethylstannyl)copper reagent (44) This reaction was performed as outlined in general procedure M. From 32.9 mg (0.3 mmol) of the acetylenic amide 200 and 58 uL (0.5 mmol) of l-bromo-3-methyl-2-butene there was obtained 77.2 mg (78%) of the prenylated amide 228 as a colorless o i l . This material was identical (glc, t i c , *H nmr) with that prepared in (a) above. Preparation of (E_)-N,N,2-Trimethyl-3-trimethylstannyl-2-pentenamide (229) This material was prepared according to general procedure M outlined above. From 33.9 mg (0.3 mmol) of N,N-dimethyl-2-pentynamide (201) and 31 uL (0.5 mmol) of iodomethane there was obtained (air-bath d i s t i l l a t i o n temperature 135-138°C/12 Torr) 63.4 mg (77%) of the unsaturated amide 229 as a colorless o i l . This material exhibited i r (film): 1625, 1385, 1265, 1130, 1080, 770 cm-1; h nmr (80 MHz, CDC13) 6: 0.18 (s, 9H, -SnMe3, J s n _ H = 52/54 Hz), 0.90 (t, 3H, -CH2CH3, J = 7.5 Hz), 1.88 (broad s, 3H, vinyl methyl protons), 2.21 (broad q, 2H, -CH2CH3, J = 7.5 Hz, J s n _ H = 47 Hz), 2.94, 2.96 (s, s, 3H each, -NMe2). Exact Mass calcd. for C10H20NOSn (M+-CH3): 290.0567; found: 290.0569. Me 3Sn Me Et CONMe 2 - 238 -Preparation of (E)-N,N-Dimethyl-2-(2-propenyl)-3-trimethylstannyl-2-pentenamide (230) This material was prepared as described i n general procedure M outlined above. From 37.0 mg (0.3 mmol) of the acetylenic amide 201 and 43 uL (0.5 mmol) of 3-bromopropene there was obtained (air-bath d i s t i l -l a t i o n temperature 135-140°C/12 Torr) 77.1 mg (79%) of the unsaturated amide 230 as a c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 1625, 1390, 1135, 775 cm"1; XH nmr (400 MHz, CDC1 3) 6: 0.24 (s, 9H, -SnMe3, i n - H = 52/54 Hz), 0.95 ( t , 3H, -CH 2CH 3, J = 7.5 Hz), 2.16 (m, 2H, -CH 2CH 3), 2.88, 3.17 (broad s, broad s, IH each, H A), 2.95, 2.97 (s, s, 3H each, -NMe2), 5.01 (d of d of t, IH, Hg, J g D = 10 Hz, J g C = 1.8 Hz, J^g = 1 Hz), 5.08 (d of d of t, IH, H c, = 17 Hz, J g C = 1.8 Hz, = 1.5 Hz), 5.77 (d of d of t, IH, H D, = 17 Hz, J g D = 10 Hz, = 7 Hz). Exact Mass calcd. f or C 1 2H 2 2NOSn (M +-CH 3): 316.0724; found: 316.0721. Preparation of (E_)-N,N-Dimethyl-2-(2-methyl-2-propenyl)-3-trimethyl-stannyl-2-pentenamide (231) 2 Et C O N M e 2 - 2 3 9 -This material was prepared as described i n general procedure M. From 37.2 mg (0.3 mmol) of N,N-dimethyl-2-pentynamide (201) and 57 yiL (0.5 mmol) of 3-iodo-2-methylpropene there was obtained ( a i r - b a t h d i s t i l l a t i o n temperature 142-146°C/12 Torr) 79.2 mg (77%) of the unsaturated amide 231 as a c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 1625, 1390, 775 cm - 1; *H nmr (400 MHz, CDC1 3) 6: 0.24 (s, 9H, -SnMe3, J g n _ H = 52/54 Hz), 0.97 ( t , 3H, -CH 2CH 3, J = 7.5 Hz), 1.76 (broad s, 3H, v i n y l methyl protons), 2.20 (q, 2H, -CH^CHg, J = 7.5 Hz), 2.85, 3.05 (broad s, broad s, IH each, a l l y l i c methylene protons), 2.95 (s, 6H, -NMe2), 4.81 (broad s, 2H, v i n y l protons). Exact Mass calcd. for C 1 3H 2itN0Sn (M +-CH 3): 330.0880; found: 330.0883. Preparation of (E_)-5-(2-Cyclopentenyl)-N,N,2-trimethyl-3-trimethyl-stannyl-2-pentenamide (232) To a cold (-78°C), s t i r r e d solution of the (t r i m e t h y l s t a n n y l ) -copper reagent (44) (2.38 mmol) in 20 mL of dry THF was added a THF solution (2 mL) of the pentynamide 202 (303 rag, 1.58 mmol). The reaction mixture was s t i r r e d at -78°C for 3 h. Dry hexamethylphospho-ramide (3 mL) and iodomethane (0.16 mL, 2.7 mmol) were added and the reaction mixture was s t i r r e d at -78°C f o r 3 h, then was allowed to - 240 -slowly warm to room temperature and s t i r r e d at that temperature for 12 h. Saturated basic aqueous ammonium chloride (5 mL) and ether (80 mL) were added and the mixture was vigorously s t i r r e d for a few minutes before the layers were separated. The organic layer was washed succes-s i v e l y with saturated basic aqueous ammonium chloride (20 mL), saturated aqueous copper sulfate (3 x 20 mL), saturated basic aqueous ammonium chloride (20 mL) and dried over anhydrous magnesium s u l f a t e . Removal of the solvent gave a c o l o r l e s s o i l which contained, on the basis of glc (column B) analysis, hexamethylditin and a mixture of the protonated pentenamide 219 and the methylated pentenamide 232 in a r a t i o of 2:98, r e s p e c t i v e l y . Subjection of t h i s material to f l a s h chromatography on s i l i c a gel (80 g, e l u t i o n with petroleum ether-ether, 1:1) provided a c o l o r l e s s o i l which upon d i s t i l l a t i o n (air-bath temperature 131-138°C/ 0.2 Torr) yielded 458 mg (78%) of the desired unsaturated amide 232. This material exhibited i r ( f i l m ) : 1625, 1395, 1110, 770, 720 cm - 1; lH nmr (400 MHz, CDC 13) 6: 0.22 (s, 9H, -SnMe3, Jgn-H = 52/54 Hz), 1.10-1.54 (m, 3H), 1.91 (s, 3H, v i n y l methyl protons), 1.96-2.06 (m, IH), 2.10-2.19 and 2.20-2.38 (m, m, 2H each, a l l y l i c methylene protons), 2.53-2.66 (m, IH, a l l y l i c methine proton), 2.96, 2.98 (s, s, 3H each, -NMe2), 5.58-5.67 and 5.67-5.75 (m, m, IH each, o l e f i n i c protons). Exact Mass calcd. for C 1 5H 2 6N0Sn (M +-CH 3): 356.1036; found: 356.1032. - 241 -Preparation of (E_)-5-(2-Cyclopentenyl)-N,N-dimethyl-2-ethyl-3-trimethyl-stannyl-2-pentenamide (247) To a cold (-78°C), s t i r r e d solution of lithium 2,2,6,6-tetra-methylpiperidide (0.31 mmol) in 3 mL of dry THF was added 0.1 mL (0.5 mmol) of dry hexamethylphosphoramlde. The solu t i o n was s t i r r e d at -78°C for 20 min. A THF solution (1 mL) of the amide 232_ (97.0 mg, 0.26 mmol) was added and the r e s u l t i n g bright yellow so l u t i o n was s t i r r e d at -78°C for 40 min. Iodomethane (25 uL, 0.4 mmol) was added and the solu t i o n was s t i r r e d at -78°C for 30 min and at 0°C for 30 min. Saturated aqueous ammonium chloride (3 mL) and ether (25 mL) were added and the phases were separated. The organic layer was washed successively with saturated aqueous copper sulfate ( 2 x 3 mL) and saturated aqueous ammonium chloride (3 mL) and dried over anhydrous magnesium s u l f a t e . Removal of the solvent afforded a yellow o i l which contained, on the basis of glc (column B) ana l y s i s , no s t a r t i n g material and a single major (>96%) product. Subjection of the crude o i l to f l a s h chromato-graphy on s i l i c a gel (17 g, e l u t i o n with petroleum ether-ether, 2:1), followed by concentration of the appropriate (Rf = 0.28) fr a c t i o n s and d i s t i l l a t i o n (air-bath temperature 126-135°C/0.3 Torr) of the res i d u a l material provided 89.1 mg (89%) of the 8'-methylated amide 247 as a Me3Sn Et - 242 -c o l o r l e s s l i q u i d . This material exhibited i r ( f i l m ) : 1620, 1385, 1110, 770, 720 cm - 1; *H nmr (400 MHz, CDC 13) 6: 0.22 (s, 9H, -SnMe3, Jgn-H = 52/54 Hz), 1.04 ( t , 3H, -CH 2CH 3, J = 7.5 Hz), 1.10-1.52 (m, 3H), 1.95-2.47 (m, 7H), 2.55-2.64 (ra, IH, methine proton), 2.98 and 3.00 (s, s, 3H each, -NMe2), 5.57-5.73 (m, 2H, o l e f i n i c protons). Exact Mass calcd. for Ci 6H28N0Sn (M+-CH3): 370.1193; 370.1217. Preparation of (E_)-5-(2-Cyclopentenyl)-N,N-dimethyl-2-(l-hydroxy-cyclohexyl)methyl-3-trimethylstannyl-2-pentenamide (253) Me3Sn X C0NMe 2 To a cold (-78°C), s t i r r e d s o l u t i o n of lithium 2,2,6,6-tetra-raethylpiperidide (0.23 mmol) in 3 mL of dry THF was added 0.1 mL (0.5 ramol) of hexamethylphosphoramide. The solution was s t i r r e d at -78°C for 20 min. A THF solution (0.5 mL) of the unsaturated amide 232 (71.0 mg, 0.19 mmol) was added and the r e s u l t i n g bright yellow so l u t i o n was s t i r r e d at -78°C for 40 min. Cyclohexanone (28 uL, 0.28 mmol) was added and the sol u t i o n , which became c o l o r l e s s within a few minutes, was s t i r r e d at -78°C for 30 min and at 0°C for 30 min. Saturated aqueous sodium bicarbonate (3 mL) and ether (25 mL) were added and the phases were separated. The organic layer was washed successively with - 243 -saturated aqueous copper s u l f a t e ( 2 x 3 mL) and saturated basic aqueous ammonium chloride (3 mL) and dried over anhydrous magnesium s u l f a t e . Removal of the solvent afforded a yellow o i l which contained, on the basis of glc (column B) analysis, some s t a r t i n g material (6%) and a major longer retention-time product. Subjection of the crude o i l to f l a s h chromatography on s i l i c a gel (2 x 15 cm column; e l u t i o n with dichloromethane-ether, 20:1) followed by concentration of the appropriate (Rf = 0.31) f r a c t i o n s and d i s t i l l a t i o n ( a ir-bath temperature = 145°C/0.2 Torr) of the residual material afforded 64.4 mg (72%) of the hydroxy amide 253 as a c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 3400 (broad), 1600, 1395, 760 cm - 1; XH nmr (80 MHz, CDC1 3) 6: 0.25 (s, 9H, -SnMe3, Js n_ H = 51/53 Hz), 0.9-1.9 (m, 13H), 1.9-2.7 (m, 8H), 2.98 and 2.99 (s, s, 3H each, -NMe2), 5.5-5.8 (m, 2H, o l e f i n i c protons). Exact Mass calcd. for C2lH3 6N0 2Sn (M +-CH 3): 454.1768; found: 454.1771. VII. Preparation of a)-Substltuted 2-Trimethylstannyl-l-alkenes Preparation of 8-Tetrahydropyranyloxy-l-octyne (277) H-C5C-(CH 2) 6-0THP To a cool (10°C), s t i r r e d suspension of l i t h i u m a c e t y l i d e -ethylenediamine complex (5.81 g, 60 mmol) i n 40 mL of dry dimethyl - 244 -sulfoxide (DMSO) was added dropwise 13.25 g (50 mmol) of l-bromo-6-tetrahydropyranyloxyhexane* (276) over a period of 30 min. After the addition was complete, the dark brown slurry was allowed to warm to room temperature and stirred at that temperature for 2 h. Water (25 mL) was added dropwise. The resulting mixture was diluted with water (100 mL) and extracted thoroughly with ether (3 x 100 mL). The combined extracts were washed with water (3 x 50 mL) and dried over anhydrous magnesium sulfate. Removal of the solvent, followed by d i s t i l l a t i o n (air-bath temperature 105-110°C/0.9 Torr) of the residual yellow o i l afforded 8.12 g (77%) of the terminal acetylene 277 as a colorless o i l . This material exhibited i r (film): 3290, 2100, 1140, 1120, 1080, 1035 cm-1; lH nmr (80 MHz, CDC13) 6: 1.2-1.9 (diffuse m, 14H), 1.93 (t, IH, C=CH, J = 2.5 Hz), 2.0-2.4 (m,' 2H, -C=CCH2-), 3.2-4.1 (m, 4H, -0CH2-), 4.55 (broad s, IH, methine proton). Exact Mass calcd. for C 1 3H 2 20 2: 210.1620; found: 210.1607. General Procedure N: Addition of the (Trimethylstannyl)copper Reagent (44) to 1-Alkynes in the Presence of Methanol. Preparation of 2-Trimethylstannyl-l-alkenes Me3Sn H * I am very grateful to Professor 1^ Weiler and Ms. M.E. Alderdice for a generous gift of this compound - 245 -To a cold (-78°C), s t i r r e d solution of the (trimethylstannyD-copper reagent (44) (0.40 mmol) In 3 mL of dry THF was added a THF sol u t i o n (0.5 mL) of the appropriate 1-alkyne (0.2 mmol) followed by anhydrous methanol (0.50 mL, 12 mmol). The dark red reaction mixture was s t i r r e d at -78°C for 10 min and at -63°C f o r 12 h. Saturated basic aqueous ammonium chloride (5 mL) and ether (20 mL) were added and the mixture was allowed to warm to room temperature with vigorous s t i r r i n g . S t i r r i n g was maintained u n t i l the aqueous phase became deep blue. The layers were separated and the aqueous phase was extracted with ether (2 x 5 mL). The combined organic solution was washed with saturated basic aqueous ammonium chloride ( 2 x 5 mL), and dried over anhydrous magnesium su l f a t e . Removal of the solvent afforded a crude o i l which contained, on the basis of glc (column B) analysis, hexamethylditin and a major product, along with a minor (1 to 12%) component having a s l i g h t l y longer retention time. Subjection of th i s o i l to eit h e r column chromatography or f l a s h chromatography on s i l i c a gel followed by concentration of the appropriate f r a c t i o n s and bulb-to-bulb d i s t i l l a t i o n of the res i d u a l material furnished the corresponding 2-triraethyl-stannyl-l-alkene. The minor component, probably the corresponding (E_) 1-trimethylstannyl-l-alkene, was not i s o l a t e d i n most cases. Preparation of 8-Tetrahydropyranyloxy-2-trimethylstannyl-l-octene (280) H A SnMe, - 246 -Following general procedure N outlined above, 8-tetrahydro-pyranyloxy-l-octyne (277) (39.4 mg, 0.2 mmol) was converted into a 95:5 mixture of two products. Subjection of the crude o i l to f l a s h chromato-graphy on s i l i c a gel (2 x 15 cm column, e l u t i o n with petroleum ether-ether, 20:1) followed by concentration of the appropriate (Rf = 0.26) f r a c t i o n s and d i s t i l l a t i o n ( a ir-bath temperature 115-120°C/0.7 Torr) of the residual material afforded 59.3 mg (84%) of the alkene 280 as a c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 1140, 1120, 1080, 1040, 915, 770 cm - 1; *H nmr (80 MHz, CDC1 3) 6; 0.13 (s, 9H, -SnMe3, J g n _ H = 52/54 Hz), 1.1-1.9 (m, 14H), 2.1-2.4 (m, 2H, a l l y l i c methylene protons), 3.2-4.0 (m, 4H, -0CH 2-), 4.5-4.7 (m, IH, methine proton), 5.12 (broad d, IH, H A, J - 3 Hz, J s n _ H = 70 Hz), 5.63 (d of t, IH, Hg, JT = 3, 1.5 Hz, Jgn-H = 156 Hz). Exact Mass calcd. for C 1 5H2g02Sn (M+-CH3): 361.1190; found: 361.1203. Preparation of 2-trimethylstannyl-l-octene (290) Following general procedure N outlined above, 1-octyne (22.0 mg, 0.2 mmol) was converted into a 94:6 mixture (glc r a t i o ) of two products. Subjection of the crude o i l to column chromatography on s i l i c a gel (4 g, e l u t i o n with petroleum ether) afforded a c o l o r l e s s - 247 -l i q u i d which upon d i s t i l l a t i o n ( air-bath temperature = 60°C/12 Torr) furnished 44.7 mg (81%) of the alkene 290. This material exhibited i r ( f i l m ) : 3010, 1460, 920, 770 cm - 1; LH nmr (80 MHz, CDC13) 6: 0.16 (s, 9H, -SnMe3, J s n - H = 52/54 Hz), 0.93 (broad t, 3H, -CH 2CH 3, J = 6 Hz), 1.1-1.5 (m, 8H), 2.29 (broad t, 2H, a l l y l i c methylene protons, J_ = 7 Hz), 5.13 (d of t, IH, H A, J = 2.5, 1 Hz, Js n_ H = 70 Hz), 5.65 (d of t, IH, Hg, J_ = 2.5, 1.5 Hz, J g n _ H = 154 Hz). Exact Mass calcd. f or C 1 0 H 2 1 S n (M +-CH 3): 261.0665; found: 261.0666. Preparation of 5-Trimethylstannyl-5-hexen-l-ol (292) Following general procedure N outlined above, 5-hexyn-l-ol (23.8 mg, 0.2 mmol) was converted into a 97:3 mixture (glc r a t i o ) of two products. Subjection of the crude o i l to column chromatography on s i l i c a gel (7 g, e l u t i o n with petroleum ether-ether, 3:1) followed by concentration of the appropriate (Rf = 0.27) f r a c t i o n s and d i s t i l l a -t i o n (air-bath temperature 80-83°C/12 Torr) of the residual material afforded 54.2 mg (85%) of the alcohol 292 as a c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 3300 (broad), 1060, 920, 770 cm"1; lE nmr (80 MHz, CDC1 3) 6: 0.17 (s, 9H, -SnMe3, J s n _ H = 52/54 Hz), 1.25 ( t , - 248 -IH, -OH, J = 5 Hz), 1.4-1.7 (m, 4H), 2.32 (broad t, 2H, a l l y l i c methy-lene protons, J = 7 Hz), 3.65 (d of t, 2H, -CH2OH, J = 5, 6 Hz), 5.14 (d of t, IH, H A, J = 2.8, 1 Hz, J g n _ H = 70 Hz), 5.65 (d of t, IH, H R, J_ = 2.8, 1.5 Hz, Jgn-H = 1 5 2 H z ^ * Exact Mass calcd. for C 8H 1 7OSn (M +-CH 3): 249.0302; found: 249.0302. Preparation of 6-Chloro-2-trimethylstannyl-l-hexene (294) Following general procedure N outlined above, 6-chloro-l-hexyne (284) (22.5 mg, 0.2 mmol) was converted into a 92:8 mixture (glc r a t i o ) of two products. Subjection of the crude reaction product to column chromatography on s i l i c a gel (4 g, e l u t i o n with petroleum ether) gave a c o l o r l e s s l i q u i d which upon d i s t i l l a t i o n ( air-bath temperature 55-58°C/12 Torr) afforded 43.6 mg (80%) of the alkene 294. This material exhibited i r ( f i l m ) : *1440, 920, 775 cm - 1; XH nmr (80 MHz, CDC1 3) 6: 0.17 (s, 9H, -SnMe 3, Js n-H = 52/54 Hz), 1.4-2.0 (m, 4H), 2.32 (broad t, 2H, a l l y l i c methylene protons, J = 7 Hz, £Sn-H = ^0 Hz), 3.55 ( t , 2H, -CH2C1, J = 6 Hz), 5.17 (d of t, IH, H A, J = 2.5, 1 Hz, Jgn-H = 70 Hz), 5.67 (d of t, IH, H B, J = 2.5, 1.2 Hz, J s n _ H = 150 Hz). Exact Mass calcd. for C 8 H 1 6 3 5 C l S n (M +-CH 3): 264.9957; found: 264.9952. - 249 -Preparation of 5-t-Butyldimethylslloxy-2-trlmethylstannyl-l-pent (296) Following general procedure N outlined above, 5-t-butyldimethyl-siloxy-l-pentyne (198) (45.2 mg, 0.2 mmol) was converted into a 95:5 mixture (glc analysis) of two products. Subjection of the crude o i l to column chromatography on s i l i c a gel (7 g, e l u t i o n with petroleum ether) gave a c o l o r l e s s o i l which upon d i s t i l l a t i o n (air-bath temperature 98-103°C/12 Torr) provided 68.1 mg (82%) of the major product as a c o l o r l e s s o i l . This material was i d e n t i f i e d as the s i l y l ether 296 based on the following data. Ir ( f i l m ) : 1260, 1105, 840, 780 cm - 1; *H nmr (80 MHz, CDC1 3) 6: 0.07 (s, 6H, -SiMe 2), 0.17 (s, 9H, -SnMe3, J s n _ H = 52/54 Hz), 0.92 (s, 9H, -SiCMe 3), 1.5-1.7 (m, 2H, -CH 2CH 2CH 2-), 2.35 (broad t, 2H, a l l y l i c methylene protons, J = 7.5 Hz), 3.62 ( t , 2H, -0CH2-, J = 6 Hz), 5.16 (broad d, IH, H A, J = 2.5 Hz, iSn-H = 7 2 H z ) » 5 * 6 8 ( d o f t» 1 H » HB» 1 = 2' 5» 1 H z> iSn-H = 1 5 2 Hz). Exact Mass calcd. for C 1 3H 2 9OSiSn (M +-CH 3): 349.1010; found: 349.1011. - 250 -Preparation of 4-Trimethylstannyl-4-penten-l-ol (298) Following general procedure N outlined above, 4-pentyn-l-ol (16.4 mg, 0.2 mmol) was converted into a 98:2 mixture (glc r a t i o ) of two products. Subjection of the crude reaction product to column chromato-graphy on s i l i c a gel (7 g, e l u t i o n with petroleum ether-ether, 3:1) followed by concentration of the appropriate (Rf = 0.27) f r a c t i o n s and d i s t i l l a t i o n (air-bath temperature 72-76°C/12 Torr) of the r e s i d u a l material afforded 43.2 mg (88%) of the alcohol 298 as a c o l o r l e s s o i l . This material exhibited i r ( f i l m ) : 3300 (broad), 1060, 920, 775 cm - 1; *H nmr (80 MHz, CDC1 3) 6: 0.20 (s, 9H, -SnMe3, J s n _ H = 52/54 Hz), 1.42 ( t , IH, -OH, J = 5.5 Hz), 1.5-1.9 (m, 2H, -CH 2CH 2CH 2-), 2.40 (broad t, 2H, a l l y l i c methylene protons, £ = 7 Hz), 3.68 (d of t, 2H, -0CH2-, J_ = 5.5, 6 Hz), 5.20 (d of t, IH, H A, J = 2.5, 1 Hz, Js n _ H = 70 Hz), 5.72 (d of t, IH, Hg, J = 2.5, 1 Hz, J s n _ H = 150 Hz). Exact Mass calcd. for C 7H 1 5OSn (M +-CH 3): 235.0145; found: 235.0134. Preparation of 5-Chloro-2-trimethylstannyl-l-pentene (264) - 251 -Following general procedure N outlined above, 5-chloro-l-pentyne (20.2 mg, 0.2 mmol) was converted into an 89:11 mixture of two products. Subjection of the crude o i l to column chromatography on s i l i c a gel (4 g, e l u t i o n with petroleum ether) gave a c o l o r l e s s l i q u i d which upon d i s t i l l a t i o n (air-bath temperature - 60°C/12 Torr) afforded 42.0 mg (79%) of the alkene 264. This material exhibited i r ( f i l m ) : 1440, 920, 770 cm - 1; *H nmr (80 MHz, CDC1 3) 6: 0.16 (s, 9H, -SnMe3, j £ n _ H = 52/54 Hz), 1.7-2.1 (m, 2H, -CH 2CH 2CH 2-), 2.19 (broad t, 2H, a l l y l i c methylene protons, _J = 7 Hz), 3.52 ( t , 2H, -CH2C1, J_ = 6.5 Hz), 5.22 (d of t, IH, H A, J = 2.5, 1 Hz, J s n - H - 70 Hz), 5.72 (d of t, IH, H B, J = 2.5, 1 Hz, Jgn -H = 148 Hz). Exact Mass calcd. for C 7 H l i 4 3 5 C l S n (M +-CH 3): 252.9840; found: 252.9823. From a s i m i l a r reaction performed i n the absence of methanol and using aged (several months) copper bromide-dimethyl s u l f i d e complex, the major product was not the expected alkene 264 but a much hi g h e r - b o i l i n g product. A small amount of t h i s compound was i s o l a t e d by f r a c t i o n a l d i s t i l l a t i o n ( air-bath temperature - 120°C/12 Torr) of the crude product. The c o l o r l e s s o i l obtained was I d e n t i f i e d as ( Z ) - l , 2 - b i s -(trimethylstannyl)-5-chloro-l-pentene (278) based on the following s p e c t r a l data. I r ( f i l m ) : 1440, 1190, 770 cm"1; *H nmr (80 MHz, C D C I 3 ) 6: 0.19 (s, 9H, -SnMe 3, iSn-H = 5 2 / 5 4 H z > » ° - 2 2 (s> 9 H » "SnMe 3, £Sn-H = 50/52 Hz), 1.6-2.0 (m, 2H, -CH 2CH 2CH 2-), 2.48 (broad t, 2H, a l l y l i c methylene protons, £ = 7 Hz), 3.52 ( t , 2H, -CH2C1, J_ = 6.5 Hz), 6.68 ( t , IH, v i n y l proton, J = 1 Hz, J s n - H = 8 2 » 188/198 Hz). Exact  Mass calcd. for C 1 0 H 2 2 3 5 C l 1 1 8 S n 1 2 0 S n (M +-CH 3): 414.9448; found: 414.9430. - 252 -Preparation of 4-t-Butyldimethylsiloxy-2-trimethylstannyl-l-butene (301) Following general procedure N outlined above, 4-t-butyldimethyl-siloxy-l-butyne (34.8 mg, 0.2 mmol) was converted into a 92:8 mixture of two products. Subjection of the crude o i l to column chromatography on s i l i c a gel (8 g, e l u t i o n with petroleum ether) afforded a c o l o r l e s s o i l which upon d i s t i l l a t i o n ( a ir-bath temperature 97-105°C/12 Torr) furnished 53.4 mg (81%) of the s i l y l ether 301. This material exhibited spectral ( i r , 1H nmr) properties i d e n t i c a l with those of the compound prepared v i a s i l y l a t i o n of alcohol 255 1 ° 6. S p e c i f i c a l l y , t h i s material exhibited i r ( f i l m ) : 1250, 1100, 920, 840, 775 cm"1; H nmr (80 MHz, CDC1 3) 6 : 0.08 (s, 6H, -SiMe2), 0.16 (s, 9H, -SnMe3, Jg n-H = 52/54 Hz), 0.92 (s, 9H, -SiCMe 3), 2.50 (broad t, 2H, a l l y l i c methylene protons, J = 7 Hz), 3.65 ( t , 2H, - O C H 2 - , J = 7 Hz), 5.22 (broad d, IH, H A, J = 2.5 Hz, Jsn-H = 71 Hz), 5.70 (d of t, IH, HB, J = 2.5, 1 Hz, Js n_H = 1 5 0 H z ) « Exact Mass calcd. for C 1 2 H 2 ? 0 S i S n (M+-CH3): 335.0854; found: 335.0856. - 253 -Preparation of 3-Trimethylstannyl-3-buten-l-ol (255) [and (E)-4-Trimethylstannyl-3-buten-l-ol (303) ] Following general procedure N outlined above, 3-butyn-l-ol (15.2 mg, 0.2 mmol) was converted into a 99:1 mixture (glc r a t i o ) of two products. Subjection of the crude reaction product to f l a s h chromato-graphy on s i l i c a gel (6 g, e l u t i o n with petroleum ether-ether, 3:1), followed by concentration of the appropriate column f r a c t i o n s and d i s t i l l a t i o n ( a i r - b a t h temperature = 70°C/12 Torr) of the r e s i d u a l material gave 42.1 mg (82%) of the major component as a c o l o r l e s s o i l . The spectral properties of t h i s material were i d e n t i c a l with those of the alcohol 255, previously prepared i n our laboratories v i a another r o u t e 6 9 . S p e c i f i c a l l y , t h i s material exhibited i r ( f i l m ) : 3300 (broad), 920, 770 cm - 1; *H nmr (80 MHz, CDC1 3) 6: 0.18 (s, 9H, -SnMe3, J s n _ H = 52/54 Hz), 1.46 ( t , IH, -OH, J = 6 Hz), 2.55 (broad t, 2H, a l l y l i c methylene protons, J_ = 6 Hz, Jgn-H = 51 Hz), 3.66 (d of t, 2H, -0CH2-, J = J ' = 6 Hz), 5.32 (d of t, IH, H A, J = 1.2, 1 Hz, Jgn-H = 70 Hz), 5.77 (d of t, IH, H B, J = 1.2, 1 Hz, J s n - H = 148 Hz). Exact  Mass calcd. for C 6H 1 3OSn (M+-CH3): 220.9989; found: 220.9986. H x H x a) Small scale - 254 -b) Large scale To a cold (-78°C), s t i r r e d s o l u t i o n of the (triraethylstannyl)-copper reagent (44) (2.0 mmol) i n 15 mL of dry THF was added a THF solution (1 mL) of 3-butyn-l-ol (70.3 mg, 1.0 mmol) followed by methanol (2.5 mL, 62 mmol). The dark red reaction mixture was s t i r r e d at -78°C for 10 min and at -63°C for 12 h. Normal workup, analogous to that outlined i n general procedure N, afforded a c o l o r l e s s o i l which contained, on the basis of glc (column B) analysis, hexamethylditin and a 91:9 mixture of two products. The crude o i l was subjected to f l a s h chromatography on s i l i c a gel (17 g, e l u t i o n with petroleum ether-ether, 3:1). The major product was i s o l a t e d by concentration of the appropri-ate (Rf = 0.37) f r a c t i o n s and d i s t i l l a t i o n ( a ir-bath temperature 63-70°C/12 Torr) of the r e s i d u a l material. The c o l o r l e s s o i l obtained (191 mg, 81%) was chromatographically (glc and t i c ) and s p e c t r a l l y ( i r , *H nmr) i d e n t i c a l with the alcohol 255 prepared in (a) above. The minor, more polar component was i s o l a t e d by concentration of the appropriate (Rf = 0.24) f r a c t i o n s and d i s t i l l a t i o n (air-bath temperature 65-70°C/12 Torr) of the r e s i d u a l material. The c o l o r l e s s o i l obtained (18.7 mg, 8%) was i d e n t i f i e d as the alcohol 303 based on the following data. Ir ( f i l m ) : 3350 (broad), 1600, 1050, 990, 775 cm"1; XH nmr (400 MHz, CDC1 3) 6: 0.13 (s, 9H, -SnMe3, Js n-H = 5 3 / 5 5 Hz), 1.45 ( t , IH, -OH, J = 6 Hz), 2.42 (d of d of t, 2H, H x, J = 6.2, 1.2, 6 Hz), 3.69 (d of t, 2H, -0CH2-, J = J* = 6 Hz), 5.96 ( A part of an ABX2 system, IH, H A, J^B = 1 8 • 5 H z » £AX = 6 , 2 H z » £Sn-H = 7 2 - 255 -Hz), 6.11 (B part of an ABX2 system, IH, Hg, = 18.5 Hz, J g X = 1.2 Hz, Jsn-H = 82/86 Hz). Exact Mass calcd. f o r C 6H 1 3OSn (M+-CH3): 220.9989; found: 220.9994. Preparation of 4-Chloro-2-trimethylstannyl-l-butene (256) [and (E)-4-Chloro-l-trimethylstannyl-l-butene (304) ] H x H x Following general procedure N outlined above, 4- c h l o r o - l -b u t y n e 1 0 5 (16.4 mg, 0.2 mmol) was allowed to react with the ( t r i m e t h y l -stannyDcopper reagent (44) (0.40 mmol) under the conditions s p e c i f i e d . Normal workup afforded a c o l o r l e s s o i l which contained, according to glc (column B) analysis, hexamethylditin and an 81:19 mixture of two products. Subjection of t h i s material to column chromatography on s i l i c a gel (8 g, e l u t i o n with petroleum ether) followed by concentration of the appropriate (Rf = 0.8) f r a c t i o n s and d i s t i l l a t i o n ( a ir-bath temperature - 60°C/12 Torr) of the residual material afforded 28.0 mg (59%) of a col o r l e s s l i q u i d . This sweet-smelling material contained 2% (glc analysis) of the minor isomer and exhibited spectral ( i r , *H nmr) properties i d e n t i c a l with those of the same compound prepared i n our 6 9 l a b o r a t o r i e s v i a another route . S p e c i f i c a l l y , t h i s material showed i r ( f i l m ) : 1615, 925, 775 cm"1; *H nmr (80 MHz, CDC13) 6: 0.24 (s, 9H, - 256 --SnMe3, isn-H ~ 52/54 Hz), 2.50 (broad t, 2H, a l l y l i c methylene protons, J = 7 Hz, J s n _ H = 47 Hz), 3.58 ( t , 2H, -CH 2C1, J = 7 Hz), 5.32 (d of t, IH, H A, J = 2.2, 1 Hz, J g n _ H = 68 Hz), 5.78 (d of t, IH, Hg, J = 2.2, 1 Hz, J 5 n _ H = 144 Hz). A small amount of the minor component was i s o l a t e d by preparative glc (100°C, isothermal). The c o l o r l e s s o i l obtained was i d e n t i f i e d as (E_)-4-chloro-l-trimethylstannyl-l-butene (304) on the basis of the following data. Ir ( C H C 1 3 ) : 1600, 780 cm"1; LH nmr (400 MHz, CDCI3) 6: 0.13 (s, 9H, -SnMe3, Js n-H = 5 3 / 5 5 H z ) > 2 ' 6 0 <d o f d o f fc' 2 H> HX» 1 = 1.2, 6, 7 Hz), 3.57 ( t , 2H, -CH2C1, J = 7 Hz), 5.96 (A part of an ABX2 system, IH, H A, J^g = 18.6 Hz, J^x = 6 » ° Hz. £Sn-H = 7 1 Hz), 6.11 (B part of an ABX2 system, IH, Hg, J^g = 18.6 Hz, J g X = 1.2 Hz, Jsn-H = 8 0 / 8 4 Hz). Exact Mass calcd. for C g H 1 2 3 5 C l S n (M+-CH3): 238.9650; found: 238.9657. Preparation of (E)-3-Tetrahydropyranyloxy-l-trimethylstannylpropene (305) and 3-Tetrahydropyranyloxy-2-trimethylstannylpropene (306) To a cold (-78°C), s t i r r e d solution of the (trimethylstannyl)-- 257 -copper reagent (44) (1.5 mmol) i n 12 mL of dry THF was added the terminal alkyne J_ (140 mg, 1.0 mmol) as a solution i n 1 mL of dry THF. The dark red reaction mixture was s t i r r e d at -78°C for 6 h. Methanol (0.5 mL), saturated basic aqueous ammonium chloride (5 mL) and ether (40 mL) were added, and the r e s u l t i n g mixture was allowed to warm to room temperature with vigorous s t i r r i n g . When the aqueous phase had become deep blue, the layers were separated. The organic layer was washed with saturated basic aqueous ammonium chloride (2 x 10 mL) and dried over anhydrous magnesium s u l f a t e . Removal of the solvent gave a c o l o r l e s s o i l which contained, on the basis of glc (column B) ana l y s i s , hexa-methylditin and a mixture of two products i n a r a t i o of 70:30. This mixture was subjected to f l a s h chromatography on s i l i c a gel (2 x 15 cm column, e l u t i o n with petroleum ether-ether, 15:1). The major, less polar product was i s o l a t e d by d i s t i l l a t i o n ( a i r -bath temperature 103-110°C/12 Torr) of the residual material from the appropriate (Rf = 0.37) concentrated column f r a c t i o n s as a c o l o r l e s s o i l (177 mg, 58%). This material was i d e n t i f i e d as the 2-trimethyl-stannyl alkene 305 based on the following data. Ir ( f i l m ) : 1140, 1120, 1030, 775 cm - 1; lR nmr (80 MHz, CDC13) 6 : 0.20 (s, 9H, -SnMe3, Js n-H = 53/55 Hz), 1.4-2.0 (m, 6H), 3.4-4.0 (m, 2H, rin g -0CH 2-), 4.28 (center of AB part of an ABXZ system, 2H, J^g = 13 Hz, = J g X = 1.5 Hz, £AZ = i z ^ 1 Hz). 4.67 ( d i f f u s e m, IH, methine proton), 5.30 (d of d of d, IH, H x, Jxz = 2 - 5 H z . iAX = iBX = 1 ' 5 H z « iSn-H " 7 1 Hz), 5.86 (d of d of d, IH, H z, Jy^z = 2 ' 5 H z » iAZ = iBZ = 1 H z » J S n-H = 146 Hz). Exact Mass calcd. f o r C 1 0H 1 9O 2Sn (M +-CH 3): 2 9 1 . 0 4 0 7 ; found: 291.0408. - 258 -The minor, more polar product was i s o l a t e d by removal of the solvent from the appropriate (Rf = 0.27) f r a c t i o n s followed by d i s t i l -l a t i o n ( a i r - b a t h temperature 105-115°C/12 Torr) of the r e s i d u a l material. The c o l o r l e s s o i l obtained (66.9 mg, 22%) was I d e n t i f i e d as the 1-trimethylstannyl alkene 306 based on the following data. I r ( f i l m ) : 1600, 1030, 910, 875, 775 cm - 1; *H nmr (400 MHz, CDC1 3) 6: 0.14 (s, 9H, -SnMe3, J s n _ H = 53/55 Hz), 1.50-1.68 (m, 4H), 1.70-1.79 (m, IH), 1.82-1.93 (m, IH), 3.48-3.54, 3.86-3.92 (m, m, IH each, r i n g -0CH 2-), 4.01 (A part of an ABXY system, IH, H A, J^g = 13 Hz, = 5.2 Hz, J^y = 1 , 2 H z » ISn-H = 1 1 H z ) » 4 ' 2 7 ( B P a r t o f a n system, IH, H B, J^g = 13 Hz, J^x = 4.8 Hz, J g Y = l-5 H z > iSn-H = 11 Hz), 4.65 (d of d, IH, methine proton, £ = J' =7 Hz), 6.11 (X part of an ABXY system, IH, H x, JXY = 1 9 H z > iAX = 5 « 2 H z » £BX = 4 « 8 Hz, Js n-H = 71 Hz), 6.29 (Y part of an ABXY system, IH, H Y, £xY = 19 Hz, J^ Y = 1.2 Hz, J g Y = 1.5 Hz, Js N-H = 8 2 H z ) « Exact Mass calcd. for C 1 0H 1 9O 2Sn (M +-CH 3): 291.0407; found: 291.0406. Preparation of (E_)-3-_t-Butyldimethylsiloxy-l-trimethylstannylpropene (307) and 3-t^Butyldimethylsiloxy-2-trimethylstannylpropene (308) To a cold (-78°C), s t i r r e d s o l u t i o n of the (trimethylstannyl)-- 259 -copper reagent (44) (1.3 mmol) i n 10 mL of dry THF was added a THF sol u t i o n (1 mL) of the 1-alkyne 54_ (147 mg, 0.86 mmol). The dark red reaction mixture was s t i r r e d at -78°C for 6 h. Saturated basic aqueous ammonium chloride (5 mL) and ether (40 mL) were added and the r e s u l t i n g mixture was allowed to warm to room temperature with vigorous s t i r r i n g . S t i r r i n g was maintained u n t i l the aqueous layer became deep blue. The organic layer was separated, washed with saturated basic aqueous ammonium chloride (2 x 10 mL), and dried over anhydrous magnesium s u l f a t e . Removal of the solvent afforded a c o l o r l e s s o i l which contained, on the basis of glc (column B ) a n a l y s i s , hexamethylditin and a mixture of two products i n a r a t i o of 72:28. This mixture was subjected to f l a s h chromatography on s i l i c a gel (2 x 15 cm column, e l u t i o n with petroleum ether). D i s t i l l a t i o n ( air-bath temperature 90-95°C/12 Torr) of the material contained within the appropriate (Rf = 0.52) f r a c t i o n s gave 161 mg (55%) of the major product as a c o l o r l e s s o i l . This material was i d e n t i f i e d as the 2-trimethylstannyl alkene 307, based on the following data. Ir ( f i l m ) : 1460, 1260, 1080, 860, 840, 780 cm - 1; lU nmr (80 MHz, CDC1 3) 6: 0.07 (s, 6H, -SiMe 2), 0.15 (s, 9H, -SnMe3, J s n _ H = 53/55 Hz), 0.92 (s, 9H, -SiCMe 3), 4.32 (d of d, 2H, H A, J^g = 2 Hz, = 1 Hz, Jsn-H = 3 3 H z ) . 5.21 ( d O F FC» 1 H » % » I B C = 2 , 5 H Z ' ^ A B = 2 Hz, J s n _ H = 7 1 H z ) » 5.81 (d of t, IH, H c, = 2.5 Hz, = 1 Hz, Js n_H = !48 Hz). Exact Mass calcd. for C u H 2 5 O S i S n (M+-CH3): 321.0697; found: 321.0686. The minor, more polar (Rf = 0.33) component was i s o l a t e d as a - 260 -co l o r l e s s o i l (58.5 mg, 20%) by d i s t i l l a t i o n ( a ir-bath temperature = 95°C/12 Torr) of the material contained within the appropriate f r a c t i o n s . This material was i d e n t i f i e d as the 1-triraethylstannyl-alkene 308 based on the following data. Ir ( f i l m ) : 1600, 1260, 1130, 1100, 850, 780 cm - 1; XH nmr (400 MHz, CDC1 3) 5: 0.09 (s, 6H, -SiMe 2), 0.14 (s, 9H, -SnMe3, Js n_ H = 53/55 Hz), 0.94 (s, 9H, -SiCMe 3), 4.20 (d of d, 2H, H x, = 1.6 Hz, Jg X = 4.1 Hz, Js n _ H = 14 Hz), 6.08 (B part of an ABX2 system, IH, = 19 Hz, Jg X = 4.1 Hz, Js n-H 72/74 Hz), 6.24 (A part of an ABX2 system, IH, = 19 Hz, = 1.6 Hz, Js n_H = 82/86 Hz). Exact Mass calcd. f o r C 1 1H 2 5OSiSn (M +-CH 3): 321.0697; found: 321.0689. - 261 -REFERENCES 1. H. Gilraan, F.W. Moore, and R.G. Jones, J . Am. Chem. Soc. £3, 2482 (1941). 2. D. Seyferth and M.A. Weiner, Chem. Ind. (London), 402 (1959). 3. (a) D. Seyferth and M.A. Weiner, J. Org. Chem. 24, 1395 (1959); (b) D. Seyferth and M.A. Weiner, J. Org. Chem. 2_6, 4797 (1961). 4. D. Seyferth and H.M. Cohen, Inorg. Chem. 2_, 625 (1963). 5. D. seyferth and L.G. Vaughan, J. Am. Chem. Soc. 86_, 883 (1964). 6. D. Seyferth, R. Suzuki, C.J. Murphy, and CR. Sabet, J . Organomet. Chem. 2, 431 (1964). 7. E.J. Corey and R.H. Wollenberg, J. Org. Chem. 40, 2265 (1975). 8. S.-M.L. Chen, R.E. Schaub and C.V. Grudzinskas, J. Org. Chem. 43, 3450 (1978). 9. M. Gielen, "Recent Developments i n the Syntheses, Properties and Uses of Tetraorganotin Compounds" i n Reviews on S i l i c o n Germanium,  T i n and Lead Compounds, Vol. V, No. 2. Freund Publishing House, Ltd. Tel-Aviv. 1981. p. 5. 10. (a) A.J. Leusink, J.W. Marsman, H.A. Budding, J.G. Noltes, and G.J.M. Van Der Kerk, Reel. Trav. Chem. Pays-Bas, 84, 567 (1965); (b) A. J. Leusink, J.W. Marsman, and H.A. Budding, Reel. Trav. Chem. Pays-Bas, 84-, 689 (1965); (c) A.J. Leusink, H.A. Budding, and J.W. Marsman, J. Organomet. Chem. 9_, 285 (1967). 11. E.-I. Negishi, Organometallics i n Organic Synthesis, Vol. 1, John Wiley, New York. 1980. p. 410-412. 12. (a) M.E. Jung and L.A. Light, Tetrahedron L e t t . 2_3, 3851 (1982); (b) H.E. Ensley, R.R. Buescher, and K. Lee, J. Org. Chem. 47_, 404 (1982). 13. (a) E. Piers and I. Nagakura, Synth. Commun. _5, 193 (1975); (b) E. Piers, J.R. Grierson, C.K.. Lau, and I. Nagakura, Can. J . Chem. 60, 210 (1982). 14. (a) E. Piers and I. Nagakura, J. Org. Chem. 40, 2694 (1975); (b) E. Piers, K.F. Cheng, and I. Nagakura, Can. J. Chem. 60, 1256 (1982). 15. E. Piers and H.E. Morton, J . Org. Chem. 44, 3437 (1979). - 262 -16. E. Piers and H.E. Morton, J. Chem. Soc. Chera. Commun. 1033 (1978). 17. M. G i l l , H.P. Bainton, and R.W. Rickards, Tetrahedron L e t t . 1437 (1981). 18. E. Piers and H.E. Morton, J . Org. Chem. 45, 4263 (1980). 19. D. Seebach, Angew. Chem. Int. Ed. Engl. 18_, 239 (1979). 20. (a) G.H. Posner, Org. React. 19, 1 (1972); (b) I b i d . , 22, 253 (1975); (c) G.H. Posner, An Introduction to Synthesis Using  Organocopper Reagents, Wiley, New York, 1980. 21. R.J. Anderson, V.L. Corbin, G. C o t t e r r e l l , G.R. Cox, CA. Henrick, F. Schaub, and J.B. S i d d a l l , J. Am. Chem. Soc. 97_, 1197 (1975). 22. G. Posner, D.J. Brunelle, and L. Sinoway, Synthesis, 622 (1974). 23. W.C. S t i l l , J. Am. Chem. Soc. 99, 4836 (1977). 24. J . Hudec, J. Chera. Soc. Perkin Trans. I, 1020 (1975). 25. (a) H.O. House, CY. Chu, J.M. Wilkens, and M.J. Umen, J. Org. Chem. 40, 1460 (1975); (b) P.G.M. Wuts, Synth. Commun. U, 139 (1981). 26. H.E. Morton. Ph.D. Thesis, U n i v e r s i t y of B r i t i s h Columbia, Vancouver, B.C., 1981. 27. D.E. Sei t z , Tetrahedron L e t t . 4909 (1981). 28. (a) R.E. Atkinson, R.F. C u r t i s , and J.A. Taylor, J. Chem. Soc. (C), 578 (1967); (b) E.J. Corey, D. Floyd, and B.H. Lipshutz, J. Org. Chem. 43, 3418 (1978). 29. (a) J.-P. G o r l i e r , L. Hamon, J. L e v i s a l l e s , and J . Wagnon, J . Chem. Soc. Chem. Commun. 88 (1973). 30. W.N. Smith and E.D. Kuehn, J. Org. Chera. 38, 3588 (1973). 31. E.J. Corey and P.L. Fuchs, Tetrahedron L e t t . 3769 (1972). 32. (a) G.L. Bundy, CH. L i n , and J.C. Sih, Tetrahedron, 37, 4419 (1981); (b) M.W. Logue and K. Teng, J . Org. Chem. 47, 2549~"Tl982). 33. W.N. Smith and O.F. Beumel, J r . Synthesis, 441 (1974). 34. L.B. Young and W.S. Trahosk, J. Org. Chem. 32, 2349 (1967). - 263 -35. (a) E.J. Corey and J.A. Katzenellenbogen, J. Am. Chem. Soc. 91, 1851 (1969); (b) J.B. S i d d a l l , M. Biskup, and J.H. F r i e d , J. Am. Chem. Soc. 91_, 1 8 5 3 ( 1 9 6 9 ) ; (c) J . K l e i n and R.M. Turkel, J. Am. Chem. Soc. 9J_, 6186 (1969); (d) J . Klei n and Aminadev, J. Chem. Soc. (C), 1380 (1970); (e) M. Obayashi, K. Utimoto, and H. Nozaki, Tetrahedron Lett. 1807 (1977). 36. J.P. Marino and R.J. LInderman, J . Org. Chem. 46, 3696 (1981). 37. T.I. Moder, C.C.K. Hsu, and F.R. Jensen, J . Org. Chera. 4_5, 1008 (1980) . 38. H. Booth and J.R. Everett, J. Chem. Soc. Chem. Commun. 278 (1976). 39. P. Leoni, M. Pasquali, and C A . G h i l a r d i , J. Chem. Soc. Chem. Commun. 240 (1983). 40. J.F. Normant, G. Cahiez, C. Chuit, and J . V i l l i e r a s , J . Organomet. Chem. 77_, 269 (1974). 41. (a) E.J. Bulten, H.A. Budding, and J.G. Noltes, J. Organomet. Chem. 22_, C5 (1970); (b) E.J. Corey and R.H. Wollenberg, J. Am. Chem. Soc. 96_, 5581 (1981); (c) E.J. Corey and R.H. Wollenberg, J. Org. Chem. 40, 3788 (1975). 42. R.R. Fraser and D.E. McGreer, Can. J. Chem. 39, 505 (1961). 43. T. Kauffmann, D. Kuhlmann, W. Sahn, and H. Schrecken, Angew, Chera. Int. Ed. Engl. 7_, 540 (1968). 44. S.D. Cox and F. Wudl, Organometalllcs, 2, 184 (1983). . 45. P.E. Sonnett, Synth. Commun. j>, 21 (1976). 46. A.C. Knipe and C.J.M. S t i r l i n g , J. Chem. Soc. (B), b7 (1968). 47. E. Pie r s , J.M. Chong and H.E. Morton, Tetrahedron L e t t . 22_, 4905 (1981) . 48. K. Gustafson and R.J. Andersen, J. Org. Chem. 47, 2167 (1982). 49. E.J. Corey and K. Achiwa, J. Org. Chem. 3_4, 3667 (1969). 50. M. Suzuki, T. Suzuki, T. Kawagishi, and -R. Noyori, Tetrahedron L e t t . 21_, 1247 (1980). 51. (a) Y. Yamaraoto and K. Maruyama, J. Am. Chem. Soc. 100, 3240 (1978); (b) Y. Yamamoto, S. Yamamoto, H. Yatagai, Y. Ishihara, and K. Maruyama, J. Org. Chem. 47, 119 (1982). 52. H.O. House and M.J. Umen, J . Org. Chem. 38, 3893 (1973). - 264 -53. R. Tanikaga, K. Miyashita, N. Ono, and A. K a j i , Synthesis, 131 (1982). 54. B.H. Lipshutz. Tetrahedron L e t t . 127 (1983). 55. S. Knapp and J. Cali e n n i , Synth. Commun. 1£, 837 (1980). 56. H.L. Vaughn and M.D. Robbins, J . Org. Chem. 40, 1187 (1975). 57. M.J.V. de O l i v e i r a Baptista, A.G.M. Barrett, D.H.R. Barton, M. Gir i j a v a l l a b h a n , R.C. Jennings, J. K e l l y , V.J. Papadimitriov, J.V. Turner, and N.A. Usher, J. Chem. Soc. Perkin Trans. I, 1477 (1977). 58. E.J. Corey and G. Schmidt, Tetrahedron Le t t , 399 (1979). 59. E. Pier s , J.M. Chong, K. Gustafson, and R.J. Andersen, Can. J. Chem. In press (1983). 60. Y. Yamamoto, H. Yatagai, and K. Karuyama, J. Org. Chem. 44, 1744 (1979). 61. L.A. Sarett, W.F. Johns, R.E. Beyler, R.M. Lukes, G.I. Poos, and G.E. Arth. J. Am. Chem. Soc. 75_, 2112 (1953). 62. (a) H. Meerwein, G. Hinz, P. Hofmann, E. Kroning and E. P f i e l , J . Prakt. Chem. 147, 17 (1937); (b) H. Meerwein, Org. Synth. C o l l . Vol. V. ed. H.E. Baumgarten, Wiley, New York, 1973. pp. 1080-2. (c) S. Hanessian, Tetrahedron L e t t . 1549 (1967). 63. (a) H.C. Brown and S. Krishnamurthy, Tetrahedron, 35, 567 (1979); (b) E.R.H. Walker, Chem. Soc. Rev. 23 (1976); (c) E. Winterfeldt, Synthesis, 617 (1975). 64. A.S. Kende and B.H. Toder, J. Org. Chem. 47_, 167 (1982). 65. J.L. Herrmann, G.R. Kieczykowski, and R.H. Schlessinger, Tetrahedron Lett. 2433 (1973). 66. D.J. Kempf, K.D. Wilson, and P. Beak, J. Org. Chem. 47_, 1612 (1982). 67. (a) J . J . F i t t and J.W. Gschwend, J. Org. Chem. 45, 4259 (1980); (b) P. Beak and D.J. Kempf, J. Am. Chem. Soc. 102, 4550 (1980). 68. (a) R.R. Fraser, A. Baignee, M. Bresse, and K. Hata, Tetrahedron L e t t . 4195 (1982); 9b) R.R. Fraser, M. Bresse, and T.S. Mansour, J. Chem. Soc. Chem. Commun. 620 (1983). 69. E. Piers and V. Karunaratne, J. Org. Chem. 48, 1774 (1983). - 265 -70. E. Piers and V. Karunaratne, J. Chem. Soc. Chem. Commun. In press (1983). 71. I.M. Downie, J.B. Holmes, and J.B. Lee, Chem. Ind. (London), 900 (1966). 72. (a) J.F. Normant, "Organocopper Reagents i n Organic Synthesis" i n New Applications of Organometallic Reagents i n Organic Synthesis, ed. D. Seyferth, p. 219, E l s e v i e r , Amsterdam (1976); (b) J.F. Normant and A. Alexakis, Synthesis, 841 (1981); (c) A. Alexakis, G. Cahiez, and J.F. Normant, J. Organomet. Chem. 177, 293 (1979); (d) A. Alexakis, G. Cahiez, and J.F. Normant, Tetrahedron, 1961 (1980); (e) A. Alexakis and J.F. Normant, Tetrahedron L e t t . 5151 (1982); M. Gardette, A. Alexakis, and J.F. Normant, Tetrahedron L e t t . 5155 (1982). 73. A. Marfat, P.R. McGuirk and P. Helquist, J. Org. Chem. 44_, 3888 (1979). 74. H. Westmijze, K. Ruitenberg, J . Meijer, and P. Vermeer, Tetrahedron Lett. 2797 (1982). 75. (a) D.H. Williams and I. Fleming, Spectroscopic Methods i n Organic  Chemistry. 2nd edn. McGraw-Hill Book Company (UK) Limited, London. 1973. p. 145; (b) i b i d , p. 100. 76. J.L. Occolowitz, Tetrahedron Le t t . 5921 (1966). 77. W.C. S t i l l , M. Kahn, and A. Mitra, J. Org. Chem. 43_, 2923 (1978). 78. A.J. Gordon and R.A. Ford, The Chemist's Companion, John Wiley and Sons, New York. 1972. p. 451. 79. Y.P. Bryan and R.H. Byrne, J. Chem. Ed. 47, 361 (1970). 80. D.D. Perr i n , W.L.F. Armarego, and D.R. P e r r i n , P u r i f i c a t i o n of  Laboratory Chemicals. 2nd edn. Pergamon Press, Oxford. 1980. 81. D.R. B u r f i e l d , K.H. Lee, and R.H. Smithers, J. Org. Chera. 42, 3060 (1977); (b) D.R. B u r f i e l d , G.H. Gan, and R.H. Smithers, J. Appl. Chem. Biotechnol. 28, 23 (1978); (c) D.R. B u r f i e l d and R.H. Smithers, J. Org. Chem. 43, 3966 (1978); (d) D.R. B u r f i e l d and R.H. Smithers, J. Chem. Technol. Biotechnol. 30, 491 (1980); (e) D.R. B u r f i e l d , R.H. Smithers, and A.S.C. Tan, J. Org. Chem. 4_6, 629 (1981); (f) D.R. B u r f i e l d and R.H. Smithers, J. Chem. Educt. 59, 703 (1982); (g) D.R. B u r f i e l d and R.H. Smithers, J . Org. Chera. 48, 2420 (1983). 82. H. Gilman and F.K. Cartledge, J. Organomet. Chera. 2, 447 (1964). 83. R.J. Cregge, J.L. Herrmann, C S . Lee, J.E. Richman, and R.H. Schlessinger, Tetrahedron Le t t . 2425 (1973). - 266 -84. B e i l s t e l n s Handbuch der Organischen Chemie. J u l i u s Springer, B e r l i n . 1920. Band I I , Syst. No. 164. 85. M.G. Dupont, Compt. rend. 148, 1522 (1909). 86. E.J. Corey and A. Venkateswarlu, J . Am. Chem. Soc. 94, 6190 (1972) . 87. G.A. Wiley, R.L. Hershkowitz, B.M. Rein, and B.C. Chung, J. Am. Chem. Soc. 86, 964 (1964). 88. D.L. Garin, J. Org. Chem. 34, 2355 (1969). 89. (a) J.H.-H. Chan and B. Rickborn, J. Am. Chem. Soc. 90, 6406 (1968); (b) J . Edelson, C.G. Skinner, J.M. Ravel, and W. Shive, Arch. Bioc. Biop. 80, 416 (1959). 90. R.A. Perry, S.C. Chen, B.C. Menon, K. Hanaya, and Y.L. Chow, Can. J. Chem. 54, 2385 (1976). 91. B e i l s t e i n s Handbuch der Organischen Chemie. J u l i u s Springer, B e r l i n . Band 2/3, p. 1722. 92. J.C. Combret, J. V i l l i e r a s , and G. L a v i e l l e , Tetrahedron L e t t . 1035 (1971). 93. R.S. Lenox and J.A. Katzenellenbogen, J. Am. Chem. Soc. 95, 957 (1973) . 94. M. Miyashita, A. Yoshikoshi, and P. Grieco, J. Org. Chem. 42_, 3772 (1977). 95. T.A. Bryson, Tetrahedron L e t t . 4923 (1973). 96. J . J . T u f a r i e l l o and E.J. Try b u l s k i , J. Org. Chem. 39, 3378 (1974). 97. Y. Veno, H. Setoi, and M. Okawara, Tetrahedron L e t t . 3753 (1978). 98. H. Bb'hme and H.P. Telhz, Arch. Pharm. 288, 343 (1955). 99. T. Hudlicky, F.J. Koszyk, T.M. Kutchan, and J.P. Sheth, J. Org. Chem. 45_, 5020 (1980). 100. S.L. Spassov, V.S. Dimitrov, M. Agova, I. Kantschovska-Dimicoli, and R. Todorova-Momcheva, Org. Mag. Res. 6^, 508 (1974). 101. L. Brandsma, Preparative Acetylenic Chemistry. E l s e v i e r , Amsterdam. 1971. p. 122. 102. CH. Lin and S.J. Stein, Synth. Commun. 6, 503 (1976). - 267 -103. B. Fischer and C A . Grob. Helv. Chim. Acta, 39, 417 (1956). 104. D. Savoia, E. T a g l i a v i n i , C. Trombini and A. Umani-Ronchi, J. Org. Chem. 45, 3227 (1980). 105. A.G. Anderson, J r . , N.E.T. Owen, F.J. Freenor, and D. Erickson, Synthesis, 398 (1976). 106. E. Piers and V. Karunaratne, personal communications. 

Cite

Citation Scheme:

        

Citations by CSL (citeproc-js)

Usage Statistics

Share

Embed

Customize your widget with the following options, then copy and paste the code below into the HTML of your page to embed this item in your website.
                        
                            <div id="ubcOpenCollectionsWidgetDisplay">
                            <script id="ubcOpenCollectionsWidget"
                            src="{[{embed.src}]}"
                            data-item="{[{embed.item}]}"
                            data-collection="{[{embed.collection}]}"
                            data-metadata="{[{embed.showMetadata}]}"
                            data-width="{[{embed.width}]}"
                            async >
                            </script>
                            </div>
                        
                    
IIIF logo Our image viewer uses the IIIF 2.0 standard. To load this item in other compatible viewers, use this url:
http://iiif.library.ubc.ca/presentation/dsp.831.1-0060687/manifest

Comment

Related Items