The Fe^III(H₂O₂) complex as a highly efficient oxidant in sulfoxidation reactions: Revival of an underrated oxidant in cytochrome P450

This work demonstrates that the Fe^III(H₂O ₂) complex, which has been considered as an unlikely oxidant in P450, is actually very efficient in sulfoxidation reactions. Thus, Fe ^III(H₂O₂) undergoes a low-barrier nucleophilic attack by sulfur on the distal oxygen, resulting in heterolytic O-O cleavage coupled to proton transfer. We further show that Fe^III(H ₂O₂) is an efficient sulfoxidation catalyst in synthetic iron porphyrin and iron corrolazine compounds. In all cases, Fe ^III(H₂O₂) performs the oxidation much faster than it converts to Cpd I and will therefore bypass Cpd I in the presence of a thioether. Thus, this paper not only suggests a plausible resolution of a longstanding issue in P450 chemistry regarding the "second oxidant" but also highlights a new mechanistic pathway for sulfoxidation reactions in P450s and their multitude of synthetic analogues. These findings have far-reaching implications for transition metal compounds, where H ₂O₂ is used as the terminal oxidant.