Methylmagnesium Iodide-Copper(I) Chloride1


[917-64-6]  · CH3IMg  · Methylmagnesium Iodide-Copper(I) Chloride  · (MW 166.25) (CuCl)

[7758-89-6]  · ClCu  · Methylmagnesium Iodide-Copper(I) Chloride  · (MW 99.00)

(methyl group transfer in 1,4- and 1,6-conjugate additions to unsaturated carbonyl compounds; coupling with acid chlorides gives methyl ketones)

Physical Data: see entries for Methylmagnesium Bromide and Copper(I) Chloride.

Preparative Methods: generated in situ by using varying, often catalytic, amounts of purified and dried CuCl.

Handling, Storage, and Precautions: air- and moisture-sensitive. Use in a fume hood.

Conjugate Additions.

While the reaction of methylmagnesium iodide with a,b-unsaturated carbonyl compounds usually produces a mixture of 1,2- and 1,4-adducts, a selective 1,4-addition is observed in the presence of copper(I) chloride in most cases. Many successful conjugate additions to acyclic2 or cyclic3-5 enones (including steroidal ketones6) as well as to enoate esters7 have been reported (eqs 1-3). A similar transformation of phenylpropiolic acid gives 3-phenyl-2-butenoic acid.8

A conjugate 1,6-addition is possible (eq 4).9

Addition to cyclic enones usually proceeds stereoselectively (eqs 1 and 2). Being irreversible, the reaction is governed by kinetic control. The stereochemical outcome can be predicted in most cases on the basis of transfer of the methyl group from the reagent perpendicular to the alkenic bond and from the least hindered side of the substrate.3c,6e

Steric hindrance may result in low yield of the addition product. Reduction of the alkenic bond7c or 1,2-addition to the carbonyl group6a have been observed as major reaction pathways for sterically hindered substrates.

Synthesis of Methyl Ketones.

Treatment of acid chlorides, including highly sterically hindered derivatives, with MeMgI in the presence of CuCl gives methyl ketones in excellent yields.10

Related Reagents.

Ethylmagnesium Bromide-Copper(I) Iodide; 1-(Trimethylsilyl)vinylmagnesium Bromide-Copper(I) Iodide; Vinylmagnesium Bromide-Copper(I) Iodide.

1. (a) Posner, G. H. OR 1972, 19, 1. (b) Erdic, E. T. T 1984, 40, 641. (c) Lipshutz, B. H.; Sengupta, S. OR 1992, 41, 135.
2. Ayyar, K. S.; Rao, G. S. CJC 1968, 46, 1467.
3. (a) Büchi, G.; Jeger, O.; Ruzicka, L. HCA 1948, 31, 241. (b) Conia, J.-M.; Salaün, J. BSF 1965, 2747. (c) Allinger, N. L.; Riew, C. K. TL 1966, 1269. (d) Salaün, J.; Conia, J.-M. BSF 1968, 3730. (e) Camus, A.; Diara, A.; Damiano, J.-C. CR(C) 1975, 280, 523.
4. (a) Balasubramanian, M.; D'Souza, A. IJC 1970, 8, 233. For the analogous reaction of isophorone with MeMgBr-CuCl see: (b) Kharasch, M. S.; Tawney, P. O. JACS 1941, 63, 2308.
5. (a) Gerig, J. T.; Roberts, J. D. JACS 1966, 88, 2791. (b) Copper(II) acetate in THF seems to be a superior catalyst for introducing an angular methyl group: Birch, A. J.; Smith, M. Proc. Chem. Soc. 1962, 356.
6. 4-En-3-ones: (a) Mori, H. CPB 1962, 10, 382. (b) Francois, P.; Levisalles, J. BSF 1968, 318. 1-En-3-ones: (c) Mori, H. CPB 1962, 10, 386. (d) Wiechert, R.; Kerb, U.; Kieslich, K. CB 1963, 96, 2765. 4-En-6-ones: (e) Mori, H. CPB 1964, 12, 1224. 16-En-20-ones: (f) Heusler, K.; Kebrle, J.; Meystre, C.; Ueberwasser, H.; Wieland, P.; Anner, G.; Wettstein, A. HCA 1959, 42, 2043. (g) Hoffsommer, R. D.; Slates, H. L.; Taub, D.; Wendler, N. L. JOC 1959, 24, 1617.
7. (a) Kundu, A. K.; Kundu, N. G.; Dutta, P. C. JCS 1965, 2749. (b) Eliel, E. L.; Knoeber, M. C. JACS 1968, 90, 3444. (c) Pandey, R. C.; Dev, S. T 1968, 24, 3829. (d) Huang, X.; Chan, C.-C.; Wu, Q.-L. TL 1982, 23, 75. (e) Tanaka, J.; Kanemasa, S.; Ninomiya, Y.; Tsuge, O. BCJ 1990, 63, 476.
8. Iwai, I.; Konotsune, T. YZ 1962, 82, 601 (CA 1963, 58, 1392a).
9. Saimoto, H.; Hiyama, T.; Nozaki, H. TL 1980, 21, 3897.
10. (a) Lion, C.; Dubois, J.-E.; Bonzougou, Y. JCR(S) 1978, 46. (b) Lion, C.; Dubois, J.-E.; Bonzougou, Y. JCR(M) 1978, 826.

Lucjan Strekowski & Yuri V. Gulevich

Georgia State University, Atlanta, GA, USA

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