[37616-22-1]  · C2H3Cu  · Vinylcopper  · (MW 90.60)

(synthesis of 1,3-dienyl esters;2 vinyl 1,4-addition to alkynic esters3 and enones4)

Alternate Name: ethenylcopper.

Preparative Methods: by the reaction of Vinyllithium or vinylmagnesium halides and a copper(I) salt.

Handling, Storage, and Precautions: sensitive to air and moisture; dimerization occurs above 0 °C. Use in a fume hood.

General Discussion.

Vinylcopper was initially prepared from Vinylmagnesium Chloride-Copper(I) Chloride in THF;5 warming the solution of vinylcopper from -40 to 20 °C results in the formation of 1,3-butadiene. Lithium Divinylcuprate was reported by House and co-workers in 1969 and shown to undergo 1,4-addition reactions with enones in very good yields.6 However, in attempts to synthesize 1,3-dienes by the addition of lithium divinylcuprate to alkynic esters, stereochemical mixtures of double bond isomers are obtained. Corey and Chen2 discovered that vinylcopper, prepared by the addition of 1 equiv of Vinyllithium to Copper(I) Iodide-diisopropyl sulfide in ether at -78 °C, efficiently adds to alkynic esters to provide the 1,3-diene product with nearly complete stereochemical control (eq 1). Vinylcopper addition to higher homologues of alkynic esters also provides the 1,4-adduct with complete stereocontrol.3

1,6-Addition of vinylcopper to 1,3-dienyl esters is also carried out at -78 to -20 °C. Quenching the reaction mixture with methanol at -20 °C provides the 3,6-heptadiene esters in greater than 95% stereochemical purity (eq 2).2 The same reaction with lithium divinylcuprate results in a 45:55 mixture of (E) and (Z) isomers of the 3,4-double bond. Vinylcopper reagents do not readily add to g-substituted unsaturated esters.6 For example, no 1,4-addition of vinylcopper is observed with ethyl 4-benzyloxy-2-pentenoate. However, diastereoselective addition to a doubly activated ester does occur in reasonable yield to provide the anti diastereomer as the major product (eq 3). Higher yields of the 1,4-addition product are observed for lithium divinylcuprate and the corresponding higher order cyanocuprate, but the diastereoselection does not improve. The reduced reactivity of the neutral vinylcopper species prepared from Vinylmagnesium Bromide and Copper(I) Bromide-dimethyl sulfide complex in THF, in comparison to that of the corresponding lithium homocuprate reagent, is advantageous in providing the 1,4-addition product in reactions with acetylenedicarboxylates.7 Cuprate reagents tend to provide low yields of the product due to competing polymerization. Vinylcopper also readily adds to 1-alkynyl sulfoxides to form vinyl sulfoxides in high yields.8 A useful method for the stereospecific formation of cis-b-substituted alkenylcopper reagents is the addition of organocopper reagents to alkynes.9,10 The substituted vinylcopper reagent obtained in this fashion may react with a second equivalent of the same alkyne or a different alkyne to form a new vinylcopper species, or may react with an alkyl halide in the presence of HMPA.9a The vinylcopper reagents prepared from alkynes can also be transformed to vinyl iodides,9b or carbonylated9c with retention of double-bond stereochemistry.

b-Substituted vinylcopper reagents derived from alkynes are also not as reactive as cuprate reagents and do not undergo 1,4-addition to enones readily. The initially formed vinylcopper species can be transformed into the more reactive cuprate by addition of an equivalent of a nontransferable ligand. Epoxides, aldehydes, and unsaturated ketones or esters can then all be used as electrophiles in subsequent reactions.9d b-Substituted enones are recalcitrant to 1,4-addition of vinylcopper or lithium divinylcuprate. Successful 1,4-addition of a vinyl group to isophorone is achieved only upon the addition of Tri-n-butylphosphine (eq 4).11 Noyori and co-workers devised an efficient three-component coupling route to the prostaglandins which involves the tributylphosphine-promoted conjugate addition of neutral vinylcopper reagents to cyclopentenones.4 A similar approach to the stereocontrolled synthesis of sterols employs a vinylcopper/tributylphosphine conjugate addition reaction (eq 5).12 The obvious advantage of the organocopper reagents over the corresponding homocuprate reagents in the synthesis of prostaglandins and sterols is the fact that only 1 equiv of the vinyl group is required. Generation of the higher order cyanocuprate from 2 equiv of vinyllithium and Copper(I) Cyanide provides the most useful reagent for conjugate addition reactions.1c

The stereoselective synthesis of dienes has also been accomplished by palladium-catalyzed coupling of neutral vinylcopper derivatives with iodoalkenes.13 Substitution reactions of allenyl iodides by vinylcopper produces nonconjugated enyne ethers which are not readily accessible by other methods (eq 6).14 Conjugated enynes have been prepared by trapping the vinylcopper reagent obtained by alkylcopper addition to an alkyne with alkynylphenyliodonium tosylates (eq 7).15 The alkene geometry is maintained in the alkynylation reaction.

Related Reagents.

3,3-Diethoxy-1-propen-2-ylcopper; Lithium Divinylcuprate; Lithium Divinylcuprate-Tributylphosphine; 1-(Trimethylsilyl)vinylmagnesium Bromide-Copper(I) Iodide; Vinylmagnesium Bromide-Copper(I) Iodide; Vinylmagnesium Chloride-Copper(I) Chloride.

1. (a) Posner, G. H. OR 1972, 19, 1. (b) Posner, G. H. OR 1975, 22, 253. (c) Lipshutz, B. H.; Sengupta, S. OR 1992, 41, 135. (d) Normant, J. F. S 1972, 63. (e) Yamamoto, Y. AG(E) 1986, 25, 947. (f) Posner, G. H. An Introduction to Synthesis Using Organocopper Reagents; Wiley: New York, 1980.
2. Corey, E. J.; Chen, R. H. K. TL 1973, 1611.
3. Corey, E. J.; Kim, C. U.; Chen, R. H. K.; Takeda, M. JACS 1972, 94, 4395.
4. Suzuki, M.; Kawagishi, T.; Noyori, R. TL 1982, 23, 5563.
5. Kauffmann, T.; Sahm, W. AG(E) 1967, 6, 85.
6. Whitesides, G. M.; Fischer, W. F., Jr.; San Filippo, J., Jr.; Bashe, R. W.; House, H. O. JACS 1969, 91, 4871.
7. Yamamoto, Y.; Chounan, Y.; Nishii, S.; Ibuka, T.; Kitahara, H. JACS 1992, 114, 7652.
8. Nishiyama, H.; Sasaki, M.; Itoh, K. CL 1981, 905.
9. Vermeer, P.; Meijer, J.; Eylander, C. RTC 1974, 93, 240.
10. (a) Normant, J. F.; Cahiez, G.; Bourgain, M.; Chuit, C.; Villieras, J. BSF(2) 1974, 1656. (b) Normant, J. F.; Cahiez, G.; Chuit, C.; Villieras, J. JOM 1974, 77, 269. (c) Normant, J. F.; Cahiez, G.; Chuit, C.; Villieras, J. JOM 1974, 77, 281. (d) Alexakis, A.; Cahiez, G.; Normant, J. F. T 1980, 36, 1961.
11. Marfat, A.; McGuirk, P. R.; Kramer, R.; Helquist, P. JACS 1977, 99, 253.
12. Hooz, J.; Layton, R. B. CJC 1970, 48, 1626.
13. Takahashi, T.; Naito, Y.; Tsuji, J. JACS 1981, 103, 5261.
14. (a) Jabri, N.; Alexakis, A.; Normant, J. F. TL 1982, 23, 1589. (b) Jabri, N.; Alexakis, A.; Normant, J. F. TL 1981, 22, 959.
15. Stang, P. J.; Kitamura, T. JACS 1987, 109, 7561.

Russell J. Linderman

North Carolina State University, Raleigh, NC, USA

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