Methylcopper-Tributylphosphine1

MeCu.PBu3

[24743-95-1]  · C13H30CuP  · Methylcopper-Tributylphosphine  · (MW 280.95)

(reagent for 1,4-addition of methyl group;2 methylation of aryl iodides;3 ring opening of b-propiolactones4)

Alternate Name: methyl(tributylphosphine)copper.

Physical Data: mp 57-60 °C; dec above 90 °C.

Preparative Methods: prepared from Methyllithium or methylmagnesium halides and Copper(I) Iodide-Tributylphosphine complex.

Handling, Storage, and Precautions: sensitive to air and moisture. Hydrolysis produces methane, which can be an explosion hazard. Handle in a fume hood.

Introduction.

House and co-workers first described the reactions of methylcopper stabilized by tributylphosphine in the 1960s.5 Yamamoto and co-workers6 carried out a comprehensive study of the formation and stability of phosphine complexes of alkylcopper species. MeCu-tributylphosphine was prepared from copper(II) acetoacetate and dimethylethoxyaluminum. The complex was isolated (mp 57-60 °C) and shown to be light- and air-sensitive. Thermal decomposition6b occurred between 90 and 130 °C with the evolution of methane (61%) and ethane (39%); ethane was presumed to arise by hydrogen abstraction from the phosphine ligands. Since ethylene was not observed, the possibility of a-elimination was excluded.

Enone Additions.

1,4-Addition of MeCu-tributylphosphine to pent-3-en-2-one in the presence of Lithium Iodide provided 4-methylpentan-2-one in 99% yield. Subsequent studies2 compared the reactivity of Methylcopper, MeCu-tributylphosphine, and MeCu-trimethyl phosphite in 1,4-additions to 5-methylcyclohex-2-enone. Methylcopper alone was unreactive, providing less than 1% of the 1,4-addition product. MeCu-tributylphosphine gave a 34% yield, while the MeCu-trimethyl phosphite reagent resulted in a 90% yield of trans-3,5-dimethylcyclohexanone (eq 1). Both of the phosphine complexes were generated in situ and required that lithium iodide be present in the reaction mixture for 1,4-addition to occur. Noyori and co-workers7 reinvestigated the 1,4-addition of tributylphosphine-stabilized organocopper reagents and determined that the best results were obtained when 2 equiv of tributylphosphine were added to the organocopper reagent. MeCu-tributylphosphine proved to be the least reactive of the alkyl copper species investigated. For example, MeCu-tributylphosphine provided the 1,4-addition product from cyclopentenone in 73% yield, while reaction with the corresponding butyl copper reagent resulted in a 93% yield of 3-butylcyclopentane.

The reactivity of MeCu-tributylphosphine has also been directly compared with that of Methylcopper-Boron Trifluoride Etherate.8 In reaction with acetylcyclohexene, MeCu-tributylphosphine provided the 1,4-addition product in 55% yield, while the MeCu-boron trifluoride complex gave the same product in 68% yield (eq 2). Only a trace of the 1,2-addition product was noted in each reaction. Interestingly, the addition of boron trifluoride to preformed MeCu-tributylphosphine did not result in improved yields of the 1,4-adduct.

These results are in contrast to the observations by Oppolzer and co-workers9 in the asymmetric 1,4-addition of MeCu-tributylphosphine to (-)-8-phenylmenthol crotonate esters (eq 3). In this study, MeCu-tributylphosphine resulted in much better yields of the 1,4-adduct and improved enantioselectivity when compared to MeCu-boron trifluoride. However, the combination of MeCu-tributylphosphine and boron trifluoride proved to be the reagent mixture of choice for asymmetric conjugate addition to a camphor-derived neopentyl ether chiral auxiliary. The asymmetric synthesis of (S)-citronellic acid was achieved using this method in 92% ee (eq 4).9 Similar results were obtained with a dicyclohexylsulfonamide chiral auxiliary, providing the methyl addition product in >94% ee (eq 5).10 This methodology can be applied to the synthesis of deoxypolypropionate derivatives in excellent optical purity.11

Displacement Reactions.

MeCu-tributylphosphine can also be used in coupling and displacement reactions. Reaction with 1-iodonaphthalene provided the methylated derivative in good yield.3 Regioselective ring opening of b-propiolactones occurs cleanly with the tributylphosphine-stabilized copper reagent (eq 6).4 MeCu-tributylphosphine also gave somewhat better results than Lithium Dimethylcuprate in the SN2 displacement of optically active allenic bromides to form optically active alkynes (eq 7).12

Related Reagents.

Copper(I) Iodide-Tributylphosphine; Lithium Dimethylcuprate; Methylcopper; Methylcopper-Boron Trifluoride Etherate; Tri-n-butylphosphine.


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. House, H. O.; Fischer, W. F., Jr., JOC 1968, 33, 949.
3. Whitesides, G. M.; Fischer, W. F., Jr.; San Filippo, J., Jr.; Bashpe, R. W.; House, H. O. JACS 1969, 91, 4871.
4. Kawashima, M.; Sato, T.; Fujisawa, T. T 1989, 45, 403.
5. House, H. O.; Respess, W. L.; Whitesides, G. M. JOC 1966, 31, 3128.
6. (a) Miyashita, A.; Yamamoto, A. BCJ 1977, 50, 1102. (b) Miyashita, A.; Yamamoto, T.; Yamamoto, A. BCJ 1977, 50, 1109.
7. (a) Suzuki, M.; Suzuki, T.; Kawagishi, T.; Noyori, R. TL 1980, 21, 1247. (b) Suzuki, M.; Suzuki, T.; Kawagishi, T.; Morita, Y.; Noyori, R. Isr. J. Chem. 1984, 24, 118.
8. Yamamoto, Y.; Yamamoto, S.; Yatagai, H.; Ishihara, Y.; Maruyama, K. JOC 1982, 47, 119.
9. Oppolzer, W.; Moretti, R.; Godel, T.; Meunier, A.; Loher, H. TL 1983, 24, 4971.
10. Oppolzer, W.; Dudfield, P.; Stevenson, T.; Godel, T. HCA 1985, 68, 212.
11. Oppolzer, W.; Moretti, R.; Bernardinelli, G. TL 1986, 27, 4713.
12. Corey, E. J.; Boaz, N. W. TL 1984, 25, 3059.

Russell J. Linderman

North Carolina State University, Raleigh, NC, USA



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