Copper-catalyzed synthesis of N-γ-lactam-substituted sulfoximines via radical cascade cyclization.

Abstract

Existing approaches to sulfoximine N-alkylation rely on N-nucleophilic substitution or direct radical trapping at nitrogen, which are hampered by harsh conditions or restricted reaction modes. Herein, we report a distinct strategy for radical N-alkylation through a copper-catalyzed radical cascade. The transformation proceeds via sequential amidyl radical generation, intramolecular 5-exo-trig cyclization, and intermolecular radical cross-coupling, enabling the formation of two C-N bonds in a single operation. The method shows broad substrate scope, accommodating both symmetrical and unsymmetrical sulfoximines, and good functional group tolerance, providing rapid access to diverse N-γ-lactam-substituted sulfoximines that combine two pharmaceutically privileged motifs.