A highly enantioselective cyanation of imines (up to >99 % ee) has been developed using well-designed C₂-symmetric hydrogen bonding catalysts. This catalytic system is distinguished by its low catalyst loading (S/C up to 1000), high efficiency, extremely broad substrate scope, scalability and mild reaction conditions.

Abstract

A highly enantioselective cyanation of imines (up to >99 % ee) has been developed using well-designed C₂-symmetric hydrogen bonding catalysts. The catalytic strategy was characterized with low catalyst loading (0.1–1 mol %), easily accessible catalysts with diverse functional groups, and catalytic base additives. A wide range of imines, including the challenging N-Boc and N-Cbz protected ketimines and aldimines, as well as fluoroalkylated ketimines, were investigated under mild conditions to afford the products with good to excellent yields (up to 99 % yield) and high enantioselectivity (up to >99 % ee). Control experiments revealed that the multiple hydrogen bonding catalysts enhanced the reactivity and enantioselectivity of the Strecker reaction initiated by the base.