Selective hydroxylation of aliphatic C–H bonds remains a challenging but broadly useful transformation. Nature has evolved systems that excel at this reaction, exemplified by cytochrome P450 enzymes which use an iron-oxo intermediate to activate aliphatic C–H bonds with k1 > 1400 s–1 at 4 °C. Many synthetic catalysts have been inspired by these enzymes and are similarly proposed to use transition metal-oxo intermediates. However, most examples of well-characterized transition metal-oxo species are not capable of reacting with strong, aliphatic C–H bonds, resulting in a lack of understanding of what factors facilitate this reactivity. Here, we report the isolation and characterization of a new terminal CoIII-oxo complex, PhB(AdIm)3CoIIIO. Upon oxidation a transient CoIV-oxo intermediate is generated that is capable of hydroxylating aliphatic C–H bonds with an extrapolated k1 for C–H activation >130 s–1 at 4 °C, comparable to values observed in cytochrome P450 enzymes. Experimental thermodynamic values and DFT analysis demonstrate that although the initial C–H activation step in this reaction is endergonic, the overall reaction is driven by an extremely exergonic radical rebound step, similar to what has been proposed in cytochrome P450 enzymes. The rapid C–H hydroxylation reactivity displayed in this well-defined system provides insight into how hydroxylation is accomplished by biological systems and similarly potent synthetic oxidants.
Selective Hydroxylation of Alkanes Catalyzed by Cytochrome P450 Enzymes
