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

Abstract

Iron(III)-hydroperoxo complexes are found in various nonheme iron enzymes as catalytic cycle intermediates; however, little is known on their catalytic properties. Recent work of Banse and coworkers on a biomimetic nonheme iron(III)-hydroperoxo complex provided evidence of its involvement in reactivity with arenes. This contrasts the behavior of heme iron(III)-hydroperoxo complexes that are known to be sluggish oxidants. In order to gain insight into the reaction mechanism of the biomimetic iron(III)-hydroperoxo complex with arenes we performed a computational (density functional theory) study. The calculations show that iron(III)-hydroperoxo reacts with substrates via low free energies of activation that should be accessible at room temperature. Moreover, dominant ketone reaction product is observed as primary products rather than the thermodynamically more stable phenols. These product distributions are analyzed and the calculations show that charge interaction between the iron(III)-hydroxo group and the substrate in the intermediate state pushes the transferring proton to the metacarbon atom of substrate and guides the selectivity of ketone formation. These studies show that the relative ratio of ketone versus phenol as primary products can be affected by external interactions of the oxidant with substrate. Moreover, iron(III)-hydroperoxo complexes are shown to selectively give ketone products, whereas iron(IV)-oxo complexes will react with arenes to form phenols instead.

Hydroxylation of Aromatics by H2O2 Catalyzed by Mononuclear Non‐heme Iron Complexes: Role of Triazole Hemilability in Substrate‐Induced Bifurcation of the H2O2 Activation Mechanism

“…[52,53] Conversely,s imilarK IE values were reported for a series of complexes involving an {Fe IV (O);O H C}c aged pair. [13,54] The magnitude of the activatione nthalpy for [(mtL 4 2 )Fe III (OOH)] 2 + decay in the absence of substrate is relatively small, and its activation entropyv ery negative compared to most literature parameters. However,l iterature systems are not ideal references for the proposed side-on decay of the intermediate:h omolytic cleavage examples correspond to the cleavage of end-on species, and heterolytic ones involve the addition of acids, which alter the intrinsic decay of Fe III (OOH).…”

“…[17,52] In contrast, we found KIE > 1i nt he case of [(mtL 4 2 )Fe III (OOH)(MeCN)] 2 + whichh as been shown to be the signature of {Fe IV (O);O H C}f ormed from [(L 5 2 )Fe III (OOH)] 2 + and similar intermediates. [13,54]…”

A Comparative Review on the Catalytic Mechanism of Nonheme Iron Hydroxylases and Halogenases

“…Then, Glu 183 participates in the heterolytic cleavage of the peroxide O-O bond to form the reactive intermediate, Compound I (C) by protonation of the hydroperoxo intermediate, Fe(III)-OOH. The latter is termed Compound 0, and has been studied extensively using various computational models [22,[34][35][36][37][38][39][40]. Interestingly, mutation of the glutamic acid residue to a histidine greatly hampers its halogenation activity [41].…”

Pathways for Arene Oxidation in Non-Heme Diiron Enzymes: Lessons from Computational Studies on Benzoyl Coenzyme A Epoxidase

“…20 The resulting cationic intermediate (e2) preferentially undergoes hydride shift to form ketone products (e3). 21 Heme Fe(III)-OOH complexes in cytochrome P450 enzymes ( Figure 1F, f1), on the other hand, were shown to be rather sluggish oxidants, poised instead toward heterolytic O-O bond breakage to form OHand porphyryl radical-Fe(IV)=O species (f2). 20,22 These latter complexes, in turn, can easily effect oxidation of aromatic rings, via a mixed electrophilic-radical attack (f3).…”