The FeIII(H2O2) Complex as a Highly Efficient Oxidant in Sulfoxidation Reactions: Revival of an Underrated Oxidant in Cytochronne 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, resulting in heterolytic O-O cleavage coupled to proton transfer. 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 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 H2O2 is used as the terminal oxidant.