Lithium Binaphtholate-Catalyzed Asymmetric Michael Reaction of Acrylamides.

Abstract

Chiral lithium binaphtholates prepared from the corresponding binaphthols and lithium tert-butoxide effectively catalyze the asymmetric Michael additions of ketones to poorly reactive acrylamides. The lithium binaphtholate catalyst mediates ketone deprotonation and enantioselective carbon-carbon bond formation to the acrylamide to deliver the Michael adduct in good yield and enantioselectivity. A small excess of lithium tert-butoxide relative to the binaphthol successfully enolizes the ketone in the initial stage of the reaction to promote the Michael reaction. Computational analysis of the transition state suggested that the 3- and 3'-phenyl groups of the binaphtholate catalyst regulate the orientation of the lithium enolate and the subsequent approach of the acrylamide, leading to superior enantioselectivity.