Oxidase catalysis via aerobically generated hypervalent iodine intermediates

The development of sustainable oxidation chemistry demands strategies to harness O₂ as a terminal oxidant. Oxidase catalysis, in which O₂ serves as a chemical oxidant without necessitating incorporation of oxygen into reaction products, would allow diverse substrate functionalization chemistry to be coupled to O₂ reduction. Direct O₂ utilization suffers from 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. This is achieved by intercepting reactive intermediates of aldehyde autoxidation to aerobically generate hypervalent iodine reagents for a broad array of substrate oxidation reactions. The use of aryl iodides as mediators of aerobic oxidation underpins an oxidase catalysis platform that couples substrate oxidation directly to O₂ reduction. We anticipate that aerobically generated hypervalent iodine reagents will expand the scope of aerobic oxidation chemistry in chemical synthesis.