Cobalt-Catalyzed Enantioselective Radical Carbamoylation of Ketimines

Abstract

Chiral amides are key motifs in pharmaceuticals and natural products, driving the need for efficient synthetic methods. Among them, those bearing tetrasubstituted stereocenters are particularly valuable yet synthetically challenging. Herein, we report a cobalt-catalyzed asymmetric carbamoyl addition to imines, providing straightforward access to structurally demanding α,α-disubstituted α-amino amides under mild conditions with excellent enantioselectivity. This modular strategy also enables a one-pot cascade to enantioenriched 2,5-diketopiperazines (DKPs), valuable scaffolds in medicinal chemistry. Mechanistic studies suggest that a stereoselective carbamoyl radical addition is the key step in chiral C–C bond formation.