Stereospecific Alkane Hydroxylation by Non-Heme Iron Catalysts:  Mechanistic Evidence for an Fe^VO Active Species

High-valent iron−oxo species have frequently been invoked in the oxidation of hydrocarbons by both heme and non-heme enzymes. Although a formally Fe^VO species, that is, [(Por^•)Fe^IVO]⁺, has been widely accepted as the key oxidant in stereospecific alkane hydroxylation by heme systems, it is not established that such a high-valent state can be accessed by a non-heme ligand environment. Herein we report a systematic study on alkane oxidations with H₂O₂ catalyzed by a group of non-heme iron complexes, that is, [Fe^II(TPA)(CH₃CN)₂]²⁺ (1, TPA = tris(2-pyridylmethyl)amine) and its α- and β-substituted analogues. The reactivity patterns of this family of Fe^II(TPA) catalysts can be modulated by the electronic and steric properties of the ligand environment, which affects the spin states of a common Fe^III−OOH intermediate. Such an Fe^III−peroxo species is high-spin when the TPA ligand has two or three α-substituents and is proposed to be directly responsible for the selective C−H bond cleavage of the alkane substrate. The thus-generated alkyl radicals, however, have relatively long lifetimes and are susceptible to radical epimerization and trapping by O₂. On the other hand, 1 and the β-substituted Fe^II(TPA) complexes catalyze stereospecific alkane hydroxylation by a mechanism involving both a low-spin Fe^III−OOH intermediate and an Fe^VO species derived from O−O bond heterolysis. We propose that the heterolysis pathway is promoted by two factors:  (a) the low-spin iron(III) center which weakens the O−O bond and (b) the binding of an adjacent water ligand that can hydrogen bond to the terminal oxygen of the hydroperoxo group and facilitate the departure of the hydroxide. Evidence for the Fe^VO species comes from isotope-labeling studies showing incorporation of ¹⁸O from H₂¹⁸O into the alcohol products. ¹⁸O-incorporation occurs by H₂¹⁸O binding to the low-spin Fe^III−OOH intermediate, its conversion to a cis-H¹⁸O−Fe^VO species, and then oxo−hydroxo tautomerization. The relative contributions of the two pathways of this dual-oxidant mechanism are affected by both the electron donating ability of the TPA ligand and the strength of the C−H bond to be broken. These studies thus serve as a synthetic precedent for an Fe^VO species in the oxygen activation mechanisms postulated for non-heme iron enzymes such as methane monooxygenase and Rieske dioxygenases.