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.