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

Abstract

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)Fe(II) 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 Fe(III)-OOH intermediate (EPR g(max) = 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 (18)O from H2(18)O, thereby excluding the possibility of a direct attack of the Fe(III)-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 Fe(V)(O)(OH) oxidant. This mechanism is supported by recent kinetic studies showing that the Fe(III)-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 Fe(V)(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 (κ(2)-acylperoxo)iron(III) species (EPR g(max) = 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 Fe(IV)(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 (κ(2)-acylperoxo)iron(III) intermediate undergoes O-O bond homolysis reversibly to form an Fe(IV)(O)((•)OC(O)R) species that decays to Fe(IV)(O) and RCO2(•) or isomerizes to its Fe(V)(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 g(max) = 2.07) may represent either of these postulated high-valent intermediates.

New Trends in Oxidative Functionalization of Carbon–Hydrogen Bonds: A Review

“…Heme and nonheme oxidation catalysts have been intensively used in oxidations of alkanes aromatics, as well as in epoxidations [171][172][173][174]. Metalloporphyrins [175][176][177][178] play a very important role in such studies; they are models of enzyme reaction centers.…”

Rapid Hydrogen and Oxygen Atom Transfer by a High-Valent Nickel–Oxygen Species

“…Interestingly, the yield significantly increased when the temperature was lowered down to -30ºC affording 44 ± 3 TON chlorocyclohexane and 9 ± 2 TON cyclohexanone, indicating that unproductive reaction pathways were occurring at higher temperatures (entry 3). Importantly, experiments in the absence of compound 1 or acetic acid afforded significantly lower yields (entries [4][5][6], indicating that all the reagents were necessary to efficiently catalyze this transformation. In order to evaluate the synthetic usefulness of this protocol, we carried out an experiment in which full conversion of the substrate could be achieved.…”

“…oxygenases) and synthetic oxidation catalysts. [1][2][3][4][5] Many examples of natural and synthetic terminal high-valent Fe-oxygen, and Mn-oxygen species have been reported in the last decade. 6,7 In sharp contrast, and despite some efforts, detection of terminal high-valent metal-oxygen species involved in the mode of action of highly efficient oxidation catalysts based on late-transition metals such as cobalt, nickel or copper are scarce.…”

Mono- and binuclear non-heme iron chemistry from a theoretical perspective

“…[7] Instead, we want to highlight current challenges in the theoretical treatment of NHFe(2) sites in biological systems -mostly metalloproteins -and correlate the enzymatic activity with the catalytic properties of the small NHFe (2) synthetic models. [8,9,10] From a theoretical perspective, the NHFe(2) systems are considered as one of the greatest challenges for contemporary computational chemistry. On top of usual problems encountered in modeling of metalloproteins, such as the construction of an appropriate model (e.g., full protein vs. cluster representing the active site), selection of the methodology [e.g., molecular dynamics (MD) sampling, combined quantum mechanical and molecular mechanical (QM/MM) techniques, free-energy perturbation, (FEP)], basis set considerations (large basis sets are required for many wave function techniques to obtain converged results), one may add the multitude of spin states available for the NHFe(2) systems [11,12] including spin-state crossings and potentially large self-interaction errors when it comes to the description at the density functional theory (DFT) level.…”