Hydroxylation of Aromatics with the Help of a Non‐Haem FeOOH: A Mechanistic Study under Single‐Turnover and Catalytic Conditions

Abstract

Ferric-hydroperoxo complexes have been identified as intermediates in the catalytic cycle of biological oxidants, but their role as key oxidants is still a matter of debate. Among the numerous synthetic low-spin Fe(III)(OOH) complexes characterized to date, [(L(5)(2))Fe(OOH)](2+) is the only one that has been isolated in the solid state at low temperature, which has provided a unique opportunity for inspecting its oxidizing properties under single-turnover conditions. In this report we show that [(L(5)(2))Fe(OOH)](2+) decays in the presence of aromatic substrates, such as anisole and benzene in acetonitrile, with first-order kinetics. In addition, the phenol products are formed from the aromatic substrates with similar first-order rate constants. Combining the kinetic data obtained at different temperatures and under different single-turnover experimental conditions with experiments performed under catalytic conditions by using the substrate [1,3,5-D(3)]benzene, which showed normal kinetic isotope effects (KIE>1) and a notable hydride shift (NIH shift), has allowed us to clarify the role played by Fe(III)(OOH) in aromatic oxidation. Several lines of experimental evidence in support of the previously postulated mechanism for the formation of two caged Fe(IV)(O) and OH(·) species from the Fe(III)(OOH) complex have been obtained for the first time. After homolytic O-O cleavage, a caged pair of oxidants [Fe(IV)O+HO(·)] is generated that act in unison to hydroxylate the aromatic ring: HO(·) attacks the ring to give a hydroxycyclohexadienyl radical, which is further oxidized by Fe(IV)O to give a cationic intermediate that gives rise to a NIH shift upon ketonization before the final re-aromatization step. Spin-trapping experiments in the presence of 5,5-dimethyl-1-pyrroline N-oxide and GC-MS analyses of the intermediate products further support the proposed mechanism.

Arene activation by a nonheme iron(III)–hydroperoxo complex: pathways leading to phenol and ketone products

“…In analogous work, Banse and coworkers [20] reported aromatic hydroxylation reactions by an iron(III)-hydroperoxo species (complex 1 in Scheme 1) with the pentadentate L 5 2 ligand (N-methyl- [21,22] and found it to react with benzene and anisole substrates efficiently. Interestingly, the use of [1,3,5-D 3 ]-benzene as a substrate probe [20], evidenced the occurrence of an NIH-shift whereby a hydrogen atom from the ipso-carbon position moved to the adjacent carbon atom, with a kinetic isotope effect (KIE) of k H /k D = 1.53 ± 0.16.…”

“…Interestingly, the use of [1,3,5-D 3 ]-benzene as a substrate probe [20], evidenced the occurrence of an NIH-shift whereby a hydrogen atom from the ipso-carbon position moved to the adjacent carbon atom, with a kinetic isotope effect (KIE) of k H /k D = 1.53 ± 0.16. Using analogous oxidants with the same probe [23] similar results were obtained.…”

Molecular Iron-Based Oxidants and Their Stoichiometric Reactions

“…Thus, the iron-based oxidants need to be distinguished from each other and from hydroxyl radicals. In the following, we will discuss some studies that have been performed, either by using isolated powders [47,58] or by employing low temperatures in combination with stopped-flow techniques [45,62,73].…”

Biodegradation of Cosmetics Products: A Computational Study of Cytochrome P450 Metabolism of Phthalates

“…The sole oxidant of P450 enzymes is CpdI. A range of experimental and computational studies have ruled out Cpd0 as an oxidant [17][18][19] (i.e., iron(III)-hydroperoxo), although recent studies on biomimetic nonheme iron(III)-hydroperoxo models have shown reactivity with arenes and halides [20][21][22]. These differences were assigned as resulting from differences in the O-O bond cleavage patterns between heme and nonheme iron(III)-hydroperoxo systems, where the hemes give favorable heterolytic cleavage and the nonhemes homolytic cleavage.…”