Electrochemical Dehydroxymethylative Functionalization of Unactivated Alcohols via Criegee–Kolbe Radical Relay

Direct dehydroxymethylative functionalization of alcohols offers a streamlined platform for molecular diversification but remains underdeveloped. An electrochemical platform operating under mild, metal-free conditions leverages a hydrogen atom transfer (HAT)/O2-Criegee relay to convert various alcohols (such as aliphatic, benzylic, and allylic alcohols) into one-carbon-shortened radicals, enabling dehydroxymethylative nitration, fluorosulfonylation, azidation, and phosphinoylation with broad functional-group tolerance and gram-scale practicality. Pairing the anodic radical generation with a cathodic Ni cycle further delivers C(sp2)-C(sp3) coupling, including the one-step methylation of aryl halides using ethanol as a feedstock methyl source. Mechanistic experiments (control studies and electron paramagnetic resonance/high-resolution mass spectrometry/cyclic voltammetry) support a sequence of HAT, O2 trapping, Criegee assembly, Baeyer-Villiger oxygenation, anodic decarboxylation, and radical interception and indicate mediator-first anodic gating. The platform expands access to C-N, C-SO2F, C-P, and C-C bonds directly from simple alcohols, providing a general strategy for selective editing of inert C-C bonds and late-stage diversification of biorelevant molecules.