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 CH amination chemistry.
