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(H₂O₂) 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, <i>resulting in heterolytic O–O cleavage coupled to proton transfer</i>. We further show that Fe^III(H₂O₂) is an efficient sulfoxidation catalyst in synthetic iron porphyrin and iron corrolazine compounds. In all cases, Fe^III(H₂O₂) performs the oxidation <i>much faster than it converts to Cpd I</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 H₂O₂ is used as the terminal oxidant