Construction of Optically Active Quaternary Propargyl Amines by Highly Enantioselective Zinc/BINOL-Catalyzed Alkynylation of Ketoimines

A general and efficient method for the highly enantioselective alkynylation of ketoimines through a zinc/1,1-bi-2-naphthol (BINOL)-catalyzed process has been developed. A variety of ketoimines, including -fluoroalkyl -imine esters, -aryl -imine esters, and trifluoromethyl aryl ketoimines, are applicable and provide their corresponding quaternary propargyl amines in excellent yields with high ee values (up to 99%ee). Both the steric and electronic effects of substituents at the 3,3 positions of BINOL are critical for the reaction efficiency and enantioselectivity. To demonstrate the usefulness of the method, (R)--CF3 -proline has been prepared in a highly efficient manner. The notable features of this protocol are its broad substrate scope, high reaction efficiency (up to 99%) and enantioselectivity (up to 99%ee), low catalyst loading (5mol% of BINOL derivative), and mild reaction conditions.