Aromatic Hydroxylation at a Non‐Heme Iron Center: Observed Intermediates and Insights into the Nature of the Active Species

Abstract

Mechanism of substrate oxidations with hydrogen peroxide in the presence of a highly reactive, biomimetic, iron aminopyridine complex, [Fe(II)(bpmen)(CH(3)CN)(2)][ClO(4)](2) (1; bpmen=N,N'-dimethyl-N,N'-bis(2-pyridylmethyl)ethane-1,2-diamine), is elucidated. Complex 1 has been shown to be an excellent catalyst for epoxidation and functional-group-directed aromatic hydroxylation using H(2)O(2), although its mechanism of action remains largely unknown. Efficient intermolecular hydroxylation of unfunctionalized benzene and substituted benzenes with H(2)O(2) in the presence of 1 is found in the present work. Detailed mechanistic studies of the formation of iron(III)-phenolate products are reported. We have identified, generated in high yield, and experimentally characterized the key Fe(III)(OOH) intermediate (λ(max)=560 nm, rhombic EPR signal with g=2.21, 2.14, 1.96) formed by 1 and H(2)O(2). Stopped-flow kinetic studies showed that Fe(III)(OOH) does not directly hydroxylate the aromatic rings, but undergoes rate-limiting self-decomposition producing transient reactive oxidant. The formation of the reactive species is facilitated by acid-assisted cleavage of the O-O bond in the iron-hydroperoxide intermediate. Acid-assisted benzene hydroxylation with 1 and a mechanistic probe, 2-Methyl-1-phenyl-2-propyl hydroperoxide (MPPH), correlates with O-O bond heterolysis. Independently generated Fe(IV)=O species, which may originate from O-O bond homolysis in Fe(III)(OOH), proved to be inactive toward aromatic substrates. The reactive oxidant derived from 1 exchanges its oxygen atom with water and electrophilically attacks the aromatic ring (giving rise to an inverse H/D kinetic isotope effect of 0.8). These results have revealed a detailed experimental mechanistic picture of the oxidation reactions catalyzed by 1, based on direct characterization of the intermediates and products, and kinetic analysis of the individual reaction steps. Our detailed understanding of the mechanism of this reaction revealed both similarities and differences between synthetic and enzymatic aromatic hydroxylation reactions.

Equilibrating (L)FeIII–OOAc and (L)FeV(O) Species in Hydrocarbon Oxidations by Bio-Inspired Nonheme Iron Catalysts Using H2O2 and AcOH

“…The subsequent generation of the Fe III –OOH complex 2a* ( k 2 and k −2 ) requires an additional equivalent of H 2 O 2 . 22, 23, 25, 54, 75, 76 This step essentially entails substitution of an –OH for an–OOH ligand via an acid-base type of transformation and is significantly faster than the previous step.…”

Dataset for Modelling Reaction Mechanisms Using Density Functional Theory: Mechanism of ortho‐Hydroxylation by High‐Valent Iron‐Oxo Species

“…Iron catalyzed hydroxylations of organic compounds have been reported by several catalysts and studied by several experimentalists and theoreticians [3][4][5][6][7][8]. The Fe III -OOH, Fe IV =O, and Fe V =O species are reported to be involved in the hydroxylation of aromatic and aliphatic compounds [3,4]. At several instances, although the presence of Fe III -OOH species has been directly detected, high-valent iron-oxo species are invoked to explain the reactivity of many mononuclear heme/nonheme iron enzymes.…”

“…Particularly in the last decade the Fe IV =O species are very popular as they have been hypothesized as potential oxidants in several aliphatic/aromatic hydroxylation reactions [9][10][11][12][13]. Besides the Fe IV =O, the Fe V =O intermediates also captured attention very recently in the hydroxylation reactions [3,4] (Figure 2).…”

“…Of particular interest here is the recently reported ortho-hydroxylation of aromatic compounds by a putative iron(V)-oxo species [3,4]. In this dataset paper, we aim to list all the data which are collected over the years to underpin this reaction mechanism.…”

{1,1′-Bis[(pyridin-2-yl)methyl]-2,2′-bipiperidyl}(perchlorato)copper(II) perchlorate

“…1. The Fe and Mn complexes ISSN 2056-9890 Figure 1 Common examples of linear tetradentate aminopyridine ligands.bearing this type of ligand show good catalytic activity for olefin epoxidation (Lyakin et al, 2012;Mikhalyova et al, 2012), as well as aromatic (Makhlynets & Rybak-Akimova, 2010) and aliphatic (Ottenbacher et al, 2015) C-H activation. Related copper(II) complexes with aminopyridine ligands have also been synthesized and characterized (Singh et al, 2017;Kani et al, 2000;Liebov et al, 2011).…”