On the Reaction Mechanism of “Higher-Order Cuprate”, Alias “Lipshutz Cuprate”

Abstract

Abstract An organocuprate reagent of the R2Cu(CN)Li composition introduced by Lipshutz has been frequently used in organic synthesis because its reactivity in some reactions is higher than that of the standard Gilman reagent R2CuLi. The higher reactivity of the Lipshutz cuprate was once ascribed to a dianionic tri-coordinated copper(I) (“higher-order”) structure, but numerous structural studies over the last ten years have shown that the Lipshutz cuprate exists as a “cyano-Gilman” (R2CuLi·LiCN) cuprate. This conclusion notwithstanding, our recent theoretical study indicated that a minor and undetectable species such as R(CN)CuLi·LiR may play some roles in the substitution and the addition reactions of the Lipshutz cuprate. The high reactivity of the minor species originates from the anisotropic and multi-coordination capability of the cyanide ligand to metals. Our result accounts for the higher or anomalous reactivity of the Lipsthuz cuprate in some reactions, and further demonstrates the importance of computational study on poly-metallic reaction pathways, where experimental mechanistic information may be difficult to obtain.