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, 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.