Methylcopper1

MeCu

[1184-53-8]  · CH3Cu  · Methylcopper  · (MW 78.59)

(nucleophilic reagent for substitution reactions;1b selective for conjugate additions;1c,d,2 adds to triple bonds3)

Physical Data: oligomeric yellow solid;4 stable at -10 °C, mp 20 °C (dec to ethane), explodes at 30-35 °C.30

Solubility: slightly sol ether, THF; sol dimethyl sulfide (DMS), tributylphosphine.

Preparative Methods: methylcopper and other alkylcopper species are most commonly prepared from equimolar amounts of alkyllithium or Grignard reagent and purified copper(I) halide in ether or THF.3a,c,5-10 The byproduct halide salts, which can influence reagent activity, are easily removed by washing the precipitated alkylcopper with fresh solvent.7,10 Alkylcoppers can be prepared from alkyl halides and highly active zero-valent copper.11

Handling, Storage, and Precautions: alkylcoppers are generally not long lived at temperatures above 0 °C. They are more thermally stable and more reactive when used in dimethyl sulfide.12 Methylcopper may decompose explosively when dry.30 Use in a fume hood.

Nucleophilic Substitutions.

Acyl chlorides are converted to the corresponding methyl ketones on treatment with methylcopper.12,13 Ring opening of heterocycles, involving SN2 processes, occurs with epoxides,11,12,14 b-lactones,15 and cyclic acetals.16 In the latter case, mandelic acid-derived 1,3-dioxolan-4-ones react with Grignard-derived alkylcoppers to deliver protected chiral secondary alcohols in good yield and 54-94% diastereomeric excess (eq 1).

Primary alkylcoppers surpass many organometallic reagents in their selectivity for SN2 substitution. Allyl halides,17 allyl ethers,9 propargyl sulfonates,18 and propargyl halides8 (eqs 2 and 3) all suffer predominately SN2 attack.

Conjugate Additions.

As with cuprate reagents, alkylcoppers undergo conjugate addition to electron-poor alkenes and alkynes. Substrates include nitroalkenes,7 alkenylsulfones,19 alkynoates,20 cyanoalkynes,21 and alkynic sulfoxides5,22 and sulfones.22a,23 With the alkynes, the reaction gives exclusively the product of cis addition across the triple bond.

The addition of alkylcopper to alkenones, alkenals, and alkenoates is accelerated by Chlorotrimethylsilane or Iodotrimethylsilane, the adducts being isolable as the silyl enol ethers.10,24,25 Chemoselectivity (1,4- vs. 1,2-addition) is also enhanced by these silanes. The enhanced rates enable the use of both alkyl groups of dialkylcuprate reagents (eq 4).24 Enhanced rate and chemoselectivity are likewise fostered by the use of stoichiometric or greater quantities of DMS12 or trialkylphosphines.20a,26

The diastereoselectivities of conjugate additions of alkylcoppers to g-alkoxyalkenoates27 and optically active alkenylsulfoximines28 have also been investigated. The sulfoximine adducts can be converted to optically active 3-alkylcarboxylic acids.

Additions to Alkynes.

Alkylcopper species add to terminal alkynes stereospecifically (syn) and with good regioselectivity to generate alkenylcopper species; subsequent addition of an electrophile provides the di- or trisubstituted alkene. The copper atom usually attaches to the 1-position in the addition step (eqs 5 and 6),9,29 but this can be influenced by directing groups and choice of solvent.3a

Related Reagents.

n-Butylmagnesium Bromide-Methylcopper(I); Lithium Dimethylcuprate; Methylcopper-Boron Trifluoride Etherate; Methylcopper-Tributylphosphine; Phenylcopper; Phenylcopper-Boron Trifluoride Etherate; Trifluoromethylcopper(I); Vinylmagnesium Bromide-Methylcopper.


1. (a) Normant, J. F. S 1972, 63. (b) Posner, G. H. OR 1975, 22, 253. (c) Posner, G. H. OR 1972, 19, 1. (d) Taylor, R. J. K. S 1985, 364.
2. House, H. O.; Respess, W. L.; Whitesides, G. M. JOC 1966, 31, 3128.
3. (a) Alexakis, A.; Normant, J.; Villieras, J. JOM 1975, 96, 471. (b) Westmijze, H.; Kleijn, H.; Vermeer, P. TL 1977, 2023. (c) McGuirk, P. R.; Marfat, A.; Helquist, P. TL 1978, 2465.
4. Westmijze, H.; George, A. V. E.; Vermeer, P. RTC 1983, 102, 322 and references therein.
5. Truce, W. E.; Lusch, M. J. JOC 1978, 43, 2252.
6. Westmijze, H.; Vermeer, P. S 1979, 390.
7. Hansson, A.-T.; Nilsson, M. T 1982, 38, 389.
8. Ruitenberg, K.; Westmijze, H.; Kleijn, H.; Vermeer, P. JOM 1984, 277, 227.
9. Kleijn, H.; Vermeer, P. JOM 1985, 292, 437.
10. Bergdahl, M.; Lindstedt, E.-L.; Nilsson, M.; Olsson, T. T 1989, 45, 535.
11. Rieke, R. D.; Wehmeyer, R. M.; Wu, T.-C.; Ebert, G. W. T 1989, 45, 443.
12. Bertz, S. H.; Dabbagh, G. T 1989, 45, 425.
13. (a) Whitesides, G. M.; Casey, C. P.; San Filippo, J.; Panek, E. J. Trans. New York Acad. Sci. 1967, 29, 572 (CA 1968, 68, 69 103g). (b) Bertz, S. H.; Dabbagh, G. CC 1982, 1030.
14. (a) Ibuka, T.; Tanaka, M.; Nemoto, H.; Yamamoto, Y. T 1989, 45, 435. (b) Tanikaga, R.; Hosoya, K.; Kaji, A. CC 1986, 836.
15. Kawashima, M.; Sato, T.; Fujisawa, T. T 1989, 45, 403.
16. Heckmann, B.; Mioskowski, C.; Yu, J.; Falck, J. R. TL 1992, 33, 5201.
17. Kang, J.; Cho, W.; Lee, W. K. JOC 1984, 49, 1838.
18. Elsevier, C. J.; Mooiweer, H. H. JOC 1987, 52, 1536.
19. Hutchinson, D. K.; Hardinger, S. A.; Fuchs, P. L. TL 1986, 27, 1425.
20. (a) Siddall, J. B.; Biskup, M.; Fried, J. H. JACS 1969, 91, 1853. (b) Klein, J.; Turkel, R. M. JACS 1969, 91, 6186.
21. Westmijze, H.; Kleijn, H.; Vermeer, P. S 1978, 454.
22. (a) Truce, W. E.; Lusch, M. J. JOC 1974, 39, 3174. (b) Kosugi, H.; Kitaoka, M.; Tagami, K.; Uda, H. CL 1985, 805. (c) Kosugi, H.; Kitaoka, M.; Tagami, K.; Takahashi, A.; Uda, H. JOC 1987, 52, 1078.
23. (a) Meijer, J.; Vermeer, P. RTC 1975, 94, 14. (b) See also: Truce, W. E.; Borel, A. W.; Marek, P. J. JOC 1976, 41, 401.
24. Matsuzawa, S.; Horiguchi, Y.; Nakamura, E.; Kuwajima, I. T 1989, 45, 349.
25. (a) Bergdahl, M.; Lindstedt, E.-L.; Nilsson, M.; Olsson, T. T 1988, 44, 2055. (b) Bergdahl, M.; Lindstedt, E.-L.; Olsson, T. JOM 1989, 365, C11.
26. Suzuki, M.; Suzuki, T.; Kawagishi, T.; Noyori, R. TL 1980, 21, 1247.
27. Yamamoto, Y.; Chounan, Y.; Nishii, S.; Ibuka, T.; Kitahara, H. JACS 1992, 114, 7652.
28. Pyne, S. G. JOC 1986, 51, 81.
29. (a) Gardette, M.; Alexakis, A.; Normant, J. F. TL 1982, 23, 5155. (b) Wijkens, P.; Vermeer, P. JOM 1986, 301, 247. (c) See also: Obayashi, M.; Utimoto, K.; Nozaki, H. JOM 1979, 177, 145.
30. Dictionary of Organometallic Compounds, 2nd ed.; Macintyre, J. E., Ed.; Chapman and Hall: New York, 1995; p 1072.

John N. Haseltine

Georgia Institute of Technology, Atlanta, GA, USA



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