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.