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Aromatic Hydroxylation at a Non‐Heme Iron Center: Observed Intermediates and Insights into the Nature of the Active Species
Author(s) -
Makhlynets Olga V.,
RybakAkimova Elena V.
Publication year - 2010
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201002577
Subject(s) - chemistry , hydroxylation , homolysis , heterolysis , reactive intermediate , bond cleavage , medicinal chemistry , stereochemistry , photochemistry , radical , catalysis , organic chemistry , enzyme
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.1, 2 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 OO 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 OO bond heterolysis. Independently generated Fe IV O species, which may originate from OO 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.