Enantioselective Organocatalyzed aza-Michael Addition Reaction of 2-Hydroxybenzophenone Imines to Nitroolefins under Batch and Flow Conditions

Abstract

Herein, an asymmetric organocatalytic aza-Michael addition reaction of ketimines to nitroolefins is presented. The use of 2-hydroxybenzophenone imine improves the enantioselective addition of N-centered nucleophiles to nitroalkenes by means of intramolecular hydrogen bond formation at the imine moiety. Moreover, the versatility of the process is demonstrated under both batch and flow conditions, showing the synthesis of a large variety of nitroamine derivatives with excellent yields and enantioselectivities. In addition, we applied this methodology to the formal synthesis of VNI, a drug-like scaffold for the treatment of Chagas disease. (Figure presented.).