Cobalt-Catalyzed Enantioconvergent Decarboxylative N-Alkylation

Abstract

Introduction of alkyl substituents onto nucleophilic nitrogen atoms in amines is a central synthetic strategy for increasing molecular complexity and structural diversity in medicinal chemistry, organic synthesis, and materials science. Although the direct transfer of a stereogenic alkyl group onto a nitrogen atom by N-alkylation is one of the most efficient approaches to asymmetric C(sp³)-N bond formation, few methods are available for the enantioconvergent N-alkylation of amines with racemic alkyl transfer reagents. We report herein a previously unexplored enantioconvergent decarboxylative N-alkylation of aromatic amines with racemic carboxylic acids. The reaction is enabled by a merger of acridine photocatalysis with Co(salen)-catalyzed asymmetric radical-polar crossover (RPC). The study provides a simple synthetic segue to medicinally and synthetically valuable α-chiral benzylic amines and unravels the structural, electronic, and bonding effects that govern the stereocontrol imparted by the privileged Co(salen)-based asymmetric RPC catalytic system.