Alkane Functionalization at Nonheme Iron Centers: Mechanistic Insights

Abstract

Biological catalysts capable of functionalizing alkanes include cytochrome P4501 (which contains a heme active site) and methane monooxygenase2 (MMO, which has a nonheme diiron active site). For cytochrome P450, an oxoiron(IV)(porphyrin cation radical) complex derived from the heterolysis of the O-O bond in an intermediate ferric peroxide is strongly implicated as the active species in the cytochrome P-450 mechanism.3 For MMO, an analogous mechanism (Figure 1) is proposed by substituting the heme center with a diiron active site.2 As has been found for cytochrome P450, Lipscomb et al. recently demonstrated that diferric MMO can hydroxylate alkanes with H2O2 via a peroxide shunt pathway, thus implicating a diferric peroxide complex in its mechanism of alkane hydroxylation.4 The peroxide intermediate is then proposed to decompose to a high valent iron-oxo species which is capable of abstracting hydrogen from alkanes. In our efforts to model the chemistry of MMO and other nonheme iron enzymes, we have explored the capabilities of a series of nonheme iron complexes to catalyze alkane functionalization chemistry and provide some mechanistic insight into this intriguing reaction.5 Modeling efforts towards this goal have entailed the combination of an iron complex with peroxide or O2/reductant.6–8 Most prominent of these are the systems developed by Barton et al.7 using iron salts collectively known as the “Gif” systems; an alkyl hydroperoxide has recently been identified to be the precursor of the alcohol and ketone products observed. This hydroperoxide is proposed to derive from O2 trapping of an alkyliron(V) species produced by the interaction of the alkane with a high valent iron-oxo species. We have been interested in the nature of the oxidizing species that is involved in alkane functionalization reactions by nonheme iron centers. In order to define more clearly the coordination environment of the metal center in such reactions, we have used iron complexes of tetradentate tripodal ligands as catalysts for the tert-butyl hydroperoxide-dependent oxidation of cyclohexane.