[61701-36-8] · C5H15Cu3Li2 · Dilithium Pentamethyltricuprate · (MW 279.69)
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.
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
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
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
Timothy J. Guzi & Timothy L. Macdonald
University of Virginia, Charlottesville, VA, USA