Bioinspired Nonheme Iron Catalysts for C-H and C=C Bond Oxidation: Insights into the Nature of the Metal-Based Oxidants

Williamson N Oloo, Larry Que

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202 Scopus citations

Abstract

Conspectus Recent efforts to design synthetic iron catalysts for the selective and efficient oxidation of C-H and C=C bonds have been inspired by a versatile family of nonheme iron oxygenases. These bioinspired nonheme (N4)FeII catalysts use H2O2 to oxidize substrates with high regio- and stereoselectivity, unlike in Fenton chemistry where highly reactive but unselective hydroxyl radicals are produced. In this Account, we highlight our efforts to shed light on the nature of metastable peroxo intermediates, which we have trapped at -40 °C, in the reactions of the iron catalyst with H2O2 under various conditions and the high-valent species derived therefrom.Under the reaction conditions that originally led to the discovery of this family of catalysts, we have characterized spectroscopically an FeIII-OOH intermediate (EPR gmax = 2.19) that leads to the hydroxylation of substrate C-H bonds or the epoxidation and cis-dihydroxylation of C=C bonds. Surprisingly, these organic products show incorporation of 18O from H218O, thereby excluding the possibility of a direct attack of the FeIII-OOH intermediate on the substrate. Instead, a water-assisted mechanism is implicated in which water binding to the iron(III) center at a site adjacent to the hydroperoxo ligand promotes heterolytic cleavage of the O-O bond to generate an FeV(O)(OH) oxidant. This mechanism is supported by recent kinetic studies showing that the FeIII-OOH intermediate undergoes exponential decay at a rate enhanced by the addition of water and retarded by replacement of H2O with D2O, as well as mass spectral evidence for the FeV(O)(OH) species obtained by the Costas group.The nature of the peroxo intermediate changes significantly when the reactions are carried out in the presence of carboxylic acids. Under these conditions, spectroscopic studies support the formation of a (κ2-acylperoxo)iron(III) species (EPR gmax = 2.58) that decays at -40 °C in the absence of substrate to form an oxoiron(IV) byproduct, along with a carboxyl radical that readily loses CO2. The alkyl radical thus formed either reacts with O2 to form benzaldehyde (as in the case of PhCH2COOH) or rebounds with the incipient FeIV(O) moiety to form phenol (as in the case of C6F5COOH). Substrate addition leads to its 2-e- oxidation and inhibits these side reactions. The emerging mechanistic picture, supported by DFT calculations of Wang and Shaik, describes a rather flat reaction landscape in which the (κ2-acylperoxo)iron(III) intermediate undergoes O-O bond homolysis reversibly to form an FeIV(O)(OC(O)R) species that decays to FeIV(O) and RCO2 or isomerizes to its FeV(O)(O2CR) electromer, which effects substrate oxidation. Another short-lived S = 1/2 species just discovered by Talsi that has much less g-anisotropy (EPR gmax = 2.07) may represent either of these postulated high-valent intermediates.

Original languageEnglish (US)
Pages (from-to)2612-2621
Number of pages10
JournalAccounts of Chemical Research
Volume48
Issue number9
DOIs
StatePublished - Aug 17 2015

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