Highly regioselective oxidation of C-H bonds in water using hydrogen peroxide by a cytochrome P450 mimicking iron complex

Cytochrome P450, one of nature's oxidative workhorses, catalyzes the oxidation of C-H bonds in complex biological settings. Extensive research has been conducted over the past five decades to develop a fully functional mimic that activates O2 or H2O2 in water to oxidize strong C-H bonds. We report the first example of a synthetic iron complex that functionally mimics cytochrome P450 in 100% water using H2O2 as the oxidant. This iron complex, in which one methyl group is replaced with a phenyl group in either wing of the macrocycle, oxidized unactivated C-H bonds in small organic molecules with very high selectivity in water (pH 8.5). Several substrates (34 examples) that contained arenes, heteroaromatics, and polar functional groups were oxidized with predictable selectivity and stereoretention with moderate to high yields (50-90%), low catalyst loadings (1-4 mol%) and a small excess of H2O2 (2-3 equiv.) in water. Mechanistic studies indicated the oxoiron(v) to be the active intermediate in water and displayed unprecedented selectivity towards 3 degrees C-H bonds. Under single-turnover conditions, the reactivity of this oxoiron(v) intermediate in water was found to be around 300 fold higher than that in CH3CN, thus implying the role water plays in enzymatic systems. Development of a molecular iron complex, which via oxoiron(v) formation, catalyzes highly efficient and regioselective oxidation of C-H bonds in water using hydrogen peroxide, and thereby acts as a functional model of cytochrome P450.

Automated summary

This study reports a synthetic iron complex that mimics cytochrome P450 in water using H2O2 as the oxidant. It shows high selectivity in oxidizing unactivated C-H bonds in small organic molecules, with predictable stereoretention and moderate to high yields. The reactivity of this iron complex in water is about 300 times higher than in organic solvents.