A dual strategy of direct C(sp3)-H sulfonamidation by cross-dehydrogenative coupling and oxidative hydroxylation-condensation

Abstract

Sulfonamides are an important class of structures, although their construction is a major challenge for the synthetic community. Herein, we report a dual strategy for direct C(sp3)-H sulfonamidation, namely, a combined cross-dehydrogenative coupling and oxidative hydroxylation/condensation. This strategy, catalyzed by n-tetrabutylammonium bromide, reduced oxidant loading to 1.0 equivalent. The reaction was mediated by MgSO4•2H2O, which improved sulfonamide yields. The practicability of this method was highlighted by its broad substrate scope, mildness, site-selectivity, gram-scalability, and capability for late-stage functionalization of drug molecules.