Oxidase Catalysis via Aerobically Generated Hypervalent Iodine Intermediates

Development of sustainable oxidation chemistry demands strategies to harness O₂ as a terminal oxidant. In particular, oxidase catalysis, in which O₂ serves as a chemical oxidant without necessitating oxygen incorporation into reaction products, would allow diverse substrate functionalization chemistry to be coupled to O₂ reduction. Direct O₂ utilization must overcome the intrinsic challenges imposed by the triplet ground state of O₂ and the disparate electron inventories of four-electron O₂ reduction and two-electron substrate oxidation. Here, we generate hypervalent iodine reagents, a broadly useful class of selective two-electron oxidants, from O₂. Synthesis of these oxidants is achieved by intercepting reactive intermediates of aldehyde autoxidation. The use of aryl iodides as mediators of aerobic oxidation underpins an oxidase catalysis platform that couples a broad array of substrate oxidations to O₂ reduction, including olefin functionalization chemistry, carbonyl a-oxidation, oxidative dearomatization, and aerobic C–H amination chemistry.