Co-Catalyzed Asymmetric Carbamoyl Radical Addition of Imines

Chiral amides are privileged motifs widely found in pharmaceuticals and natural products, spurring the development of robust synthetic methods. While carbamoyl chlorides are convenient and versatile electrophilic precursors, their application in the stereoselective synthesis of sterically hindered amides, particularly those bearing tetrasubstituted stereocenters, remains a formidable challenge. To address this, we have developed a cobalt-catalyzed asymmetric carbamoyl addition to imines, which enables efficient access to structurally demanding α,α-disubstituted α-amino amides under mild conditions with excellent enantioselectivity. Furthermore, this modular strategy facilitates a one-pot cascade to synthesize enantioenriched 2,5-diketopiperazines (DKPs), important scaffolds in medicinal chemistry. Mechanistic studies reveal stereoselective carbamoyl radical addition to forge the chiral C-C bond.