Lithium Diethylcuprate-Tributylphosphine1


[38297-20-0]  · C4H10CuLi  · Lithium Diethylcuprate-Tributylphosphine  · (MW 128.63) (Bu3P)

[998-40-3]  · C12H27P  · Lithium Diethylcuprate-Tributylphosphine  · (MW 202.36)

(representative phosphine-ligated homocuprate for 1,4-addition,2 nucleophilic substitution,3 and reductive metalation4)

Solubility: sol ether, THF.

Analysis of Reagent Purity: an assay to determine relative thermal stabilities5 can be used to estimate reagent quality and concentration: a sample of known volume and temperature is quenched with excess PhCOCl. The yield of propiophenone is measured by GC, the response of which is calibrated using authentic product and n-dodecane as internal standard.

Preparative Methods: the following general procedure has been used to prepare a variety of R2CuLi.P(n-Bu)3 reagents:6 a round-bottom flask equipped with magnetic stirring bar and rubber septum is charged with Copper(I) Iodide-Tributylphosphine.7 Under a nitrogen atmosphere, ether or THF is added. After cooling the resultant solution to -78 °C, 2.0 equiv of the appropriate RLi reagent is added dropwise. Formation of a colorless, pale pink, or yellow cuprate is immediate. Alternate preparations by addition of 1.0 equiv of Tri-n-butylphosphine to an ether or THF slurry of Copper(I) Iodide before addition of two equiv of RLi or by use of CuBr[(n-Bu)3P]28 may be possible.

Handling, Storage, and Precautions: best results are obtained with high purity CuI salts,9 dry, O2-free solvents, and alkyllithium solutions free of contaminating alkoxides or hydroxides.10 Like most alkyllithium reagents, Ethyllithium11 is pyrophoric;12 care must be exercised in its handling. Homocuprates are stabilized in the presence of stoichiometric quantities of (n-Bu)3P; there is no noticeable decomposition at -78 °C.6 Use in a fume hood.

General Discussion.

Phosphine-ligated homocuprates were introduced early in the development of organocopper chemistry.6,13 The (n-Bu)3P ligand solubilizes the homocuprate in ether solvents, increasing its reactivity, and also retards thermal decomposition. Generally, the presence of stoichiometric quantities of the ligand makes reaction workup unsatisfactory;6,13a,14 for this reason, various heterocuprates15 have found wider application in organic chemistry. Eq 1 provides a typical comparison.15

Lithium diethylcuprate-tributylphosphine has been essentially unused in organic synthesis. Phosphine-ligated organocopper reagents, however, have found recent applications in tandem vicinal dialkylation reactions leading to prostaglandins.16 Other reports suggest that the presence of a phosphine ligand during organocopper-mediated epoxide openings is important in promoting reductive metalation of substrate.4,8

Related Reagents.

Lithium Diethylcuprate; Lithium Dimethylcuprate; Lithium Divinylcuprate-Tributylphosphine.

1. (a) Lipshutz, B. H.; Sengupta, S. OR 1992, 41, 135. (b) Posner, G. H. An Introduction to Synthesis Using Organocopper Reagents; Wiley: New York, 1980.
2. (a) Perlmutter, P. Conjugate Addition Reactions in Organic Synthesis; Pergamon: New York, 1992. (b) Kozlowski, J. A. COS 1991, 4, 169. (c) Hulce, M.; Chapdelaine, M. J. COS 1991, 4, 237. (d) Chapdelaine, M. J.; Hulce, M. OR 1990, 38, 225. (e) Taylor, R. J. K. S 1985, 364. (f) Posner, G. H. OR 1972, 19, 1.
3. Posner, G. H. OR 1975, 22, 253.
4. Alexakis, A.; Marek, I.; Mangeney, P.; Normant, J. F. T 1991, 1677.
5. Bertz, S. H.; Dabbagh, G. CC 1982, 1030.
6. Whitesides, G. M.; Fischer, W. F., Jr.; San Filippo, J., Jr.; Bashe, R. W.; House, H. O. JACS 1969, 91, 4871.
7. Kaufman, G. B.; Teter, L. A. Inorg. Synth. 1963, 7, 9.
8. Mitani, M.; Matsumoto, H.; Gouda, N.; Koyama, K. JACS 1990, 112, 1286.
9. Purification methods for CuI: (a) Posner, G. H.; Sterling, J. J. JACS 1973, 95, 3076. (b) Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals, 3rd ed.; Pergamon: New York, 1988; p 322. (c) Lipshutz, B. H.; Whitney, S.; Kozlowski, J. A.; Breneman, C. M. TL 1986, 27, 4273.
10. Corey, E. J.; Naef, R.; Hannon, F. J. JACS 1986, 108, 7114.
11. (a) Brandsma, L.; Verkruijsse, H. D. Synthesis of Acetylenes, Allenes, and Cumulenes; Elsevier: New York, 1981; p 11. (b) Bryce-Smith, D.; Turner, E. E. JCS 1953, 861.
12. Wakefield, B. J. Organolithium Methods; Academic: New York, 1988; pp 11-15.
13. (a) House, H. O.; Fischer, W. F., Jr. JOC 1968, 33, 949. (b) House, H. O.; Respess, W. L.; Whitesides, G. M. JOC 1966, 31, 3128.
14. Johnson, C. R.; Dutra, G. A. JACS 1973, 95, 7777.
15. Posner, G. H.; Whitten, C. E.; Sterling, J. J. JACS 1973, 95, 7788.
16. Noyori, R.; Suzuki, M. Chemtracts-Org. Chem. 1990, 3, 173.

Martin Hulce

Creighton University, Omaha, NE, USA

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