Enantioselective Mannich Reaction of Ketone Enolates with Imines through Cooperative B/Cu Catalysis

Abstract

The nucleophilic activation of ketones containing a tethered hydroxyl group by borinic acid, through the formation of an unprecedented tetracoordinated boron enolate complex, is presented. The in situ-generated boron enolates are captured by electrophilic isatin imines, which are activated by chiral copper-based catalysts. This reaction accommodates a wide range of substrates, producing a series of 3-substituted 3-amino-2-oxindoles with a C3-tetrasubstituted stereogenic center, all in excellent yields and enantioselectivities. A plausible model for chiral induction in this reaction is proposed. The method's utility is further demonstrated by a gram-scale reaction and subsequent elaboration of the Mannich adducts.