Dilithium Pentamethyltricuprate1

Li2Cu3Me5

[61701-36-8]  · C5H15Cu3Li2  · Dilithium Pentamethyltricuprate  · (MW 279.69)

(highly regiospecific organometallic methylating agent for conjugate addition to enones2 and enals,3,4 and for displacement of allylic acetates,5 carbamates,5 and lactones6)

Solubility: sol diethyl ether to -78 °C.

Analysis of Reagent Purity: low temperature NMR spectroscopy in ether indicates a reagent of discrete Me(5):Cu(3) stoichiometry as a structurally complex aggregate.7

Preparative Method: to Copper(I) Iodide (2.0 mmol) in 5.0 mL ether at -78 °C is added a 0.95 M solution of Methyllithium (3.3 mmol). Insoluble MeCu is initially produced with 1 equiv of MeLi:CuI; subsequent addition of MeLi dissolves most MeCu; a small amount of MeCu remains after complete addition.

Handling, Storage, and Precautions: use immediately following preparation, in a fume hood.

a,b-Unsaturated Ketones.

Li2Cu3Me5, formed as an aggregate in ether when the MeLi:MeCu ratio is at least 0.66:1, is a more highly regiospecific conjugate methylating agent for a,b-unsaturated ketones than Lithium Dimethylcuprate or Dilithium Trimethylcuprate. Rates of reaction for Li2Cu3Me5 with enones are comparable to LiCuMe2 and Li2CuMe3, even in hindered systems (eq 1).2

a,b-Unsaturated Aldehydes.

Li2Cu3Me5 is more effective than LiCuMe2 for the conjugate methylation of enals (eq 2). The use of ether-pentane as solvent was found to increase the ratio of 1,4-methylation to 1,2-methylation by Li2Cu3Me5 (eq 3).3,4

Allylic Acetates, Carbamates, and Lactones.

The addition of Li2Cu3Me5 to allylic carbamates results in exclusively syn,d-methylation, while LiCuMe2 exhibits depressed regio- and stereochemical control (eq 4). The methylation of allylic acetates occurs with similar regio- and stereospecificity using either LiCuMe2 or Li2Cu3Me5; however, the displacement of allylic acetates with Li2CuMe3 or LiCuMe2 generally proceeds with less regio- and stereospecificity than the displacement of the corresponding allylic carbamates (eq 4).5

A detailed study of the methylation of various gibberellin allylic lactones by Li2Cu3Me5, (LiCuMe2)2 and (LiCu2Me3)2 revealed the following trends (eq 5): (1) attack at the tertiary position C-10 is possible only by an SN2 pathway; (2) attack at the secondary carbon C-2 is the most favored reaction, whether by SN2 or SN2 attack; and (3) the usual SN2 anti displacement8 by organocuprates can be suppressed and SN2 syn attack at C-2 can be induced by increasing the steric bulk surrounding C-3. Under these steric constraints, SN2 syn attack at a secondary site is a more favorable reaction than SN2 displacement at the tertiary carbon C-10.6

Related Reagents.

Dilithium Trimethylcuprate; Lithium Dimethylcuprate.


1. Lipshutz, B. H.; Wilhelm, R. S.; Kozlowski, J. A. T 1984, 40, 5005.
2. Ashby, E. C.; Lin, J. J.; Watkins, J. J. JOC 1977, 42, 1099.
3. Clive, D. L. J.; Farina, V.; Beaulieu, P. CC 1981, 643.
4. Clive, D. L. J.; Farina, V.; Beaulieu, P. L. JOC 1982, 47, 2572.
5. Gallina, C. TL 1982, 23, 3093.
6. Beale, M. H. JCS(P1) 1985, 1151.
7. Lipshutz, B. H.; Kozlowski, J. A.; Breneman, C. M. JACS 1985, 107, 3197.
8. Corey, E. J.; Boaz, N. W. TL 1984, 25, 3063.

Timothy J. Guzi & Timothy L. Macdonald

University of Virginia, Charlottesville, VA, USA



Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.