Electrophotocatalytic Oxygenation of Unactivated Aliphatic C–H Bonds Using Water as a Sustainable Oxygen Source

The oxygenation of aliphatic C–H bonds is a crucial transformation in synthetic chemistry, as it transforms ubiquitous alkane feedstocks into valuable ketones and alcohols. However, achieving this transformation selectively remains a formidable hurdle since the inherent inertness of C–H bonds hinders their activation, while the subtle differences in bond dissociation energies among various sites make achieving high regioselectivity difficult. Herein, we present an electrophotochemical δ-C(sp3)–H oxygenation of N-alkylsulfonamides enabled by an intramolecular guidance strategy using water as the oxygen source. This oxidant-free protocol accommodates primary, secondary, and tertiary C–H bonds across a diverse range of substrates with excellent functional group tolerance, enabling its successful application to gram-scale synthesis and the late-stage functionalization of natural products and drug derivatives. Mechanistic studies support a sequential oxidation pathway proceeding via an oxidative radical-polar crossover, wherein an initial hydroxylation event is followed by a rapid, subsequent oxidation to furnish the final ketone product.