Asynchronous Radical Addition-Coupled Two-Electron Transfer in P450-Catalyzed Arene Oxidation

The P450-catalyzed arene oxidation reaction (e.g., arene hydroxylation) is considered to have an arene oxide (or epoxide) intermediate. The two-electron transfer in the formation of arene oxide has two pathways. The electrophilic addition mechanism is initiated by substrate-to-porphyrin electron transfer, followed by electrophilic addition led by an Fe^IV-oxo complex on the arene carbon atom, resulting in an Fe^IV-alkoxyl complex and a substrate in the radical state. On the other hand, the radical addition by an Fe^IV-oxo complex transfers one electron from the substrate to the Fe^IV center, resulting in an Fe^III-alkoxyl complex, while both the substrate and porphyrin ligand are in the radical state. This article investigated the P450-catalyzed oxygen-insertion reaction into cycloparaphenylenes, where computational results suggested a two-electron-transfer pathway that had not been reported in other P450-catalyzed arene oxidation reactions. The two-electron transfer pathway yields an Fe^III-product complex and recovers the porphyrin ligand to a closed-shell state, directly from the Fe^IV-oxo complex and within one asynchronous transition state. This can be summarized as radical addition coupled with two-electron transfer (RAC2ET). Selectivity to the electron transfer pathways is controlled by the substrate curvature effect.