Mechanistic studies of aliphatic ligand hydroxylation of a copper complex by dioxygen: A model reaction for copper monooxygenases

Shinobu Itoh, Hajime Nakao, Lisa M. Berreau, Toshihiko Kondo, Mitsuo Komatsu, Shunichi Fukuzumi

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Mechanistic studies on the aliphatic ligand hydroxylation in a copper complex of tridentate ligand la {N,N-bis[2-(2-pyridyl)ethyl]-2- phenylethylamine} by O2 have been performed in order to shed light on the structure and reactivity of the active oxygen species of our functional model for copper monooxygenases (Itoh, S.; et al. J. Am. Chem. Soc. 1995, 117, 4714). When the copper complex [Cu(II)(1a)(ClO4)2] was treated with an equimolar amount of benzoin and triethylamine in CH2Cl2 under O2 atmosphere, efficient hydroxylation occurred selectively at the benzylic position of the ligand to provide oxygenated product 2a {N,N-bis[2- (2pyridyl)ethyl]-2-phenyl-2-hydroxyethylamine} quantitatively. An isotope labeling experiment using 18O2 confirms that the oxygen atom of the OH group in 2a originates from molecular oxygen. Spectroscopic analyses using UV-vis, resonance Raman, and ESR on the reaction of [Cu(I)(la)]+ and O2 at low temperature show that a μ-η22-peroxodicopper(II) complex is an initially formed intermediate. Kinetic analysis on the peroxo complex formation indicates that the reaction of the Cu(I) complex and the monomeric superoxocopper(II) species is rate-determining for the formation of the μ- η22-peroxodicopper(II) intermediate. When ligand 1a is replaced by 1,1,2,2-tetradeuterated phenethylamine derivative 1a-d4, a relatively small kinetic deuterium isotope effect (k(H)/k(D) = 1.8 at -40 °C) is observed for the ligand hydroxylation step. The rate of the hydroxylation step is rather insensitive to the p-substituent of the ligand [(PyCH2CH2)2NCH2CH2Ar, 1a Ar = C6H5; 1b Ar = p-CH3C6H4, 1c Ar = p-ClC6H4, and 1d Ar = p- NO2C6H4)], but it varies depending on the solvent (THF > acetone > CH3OH > CH2Cl2). The p-substituent, the solvent, and the kinetic deuterium isotope effects suggest that O-O bond homolysis of the μ-η22- peroxodicopper(II) intermediate is involved as a rate-determining step in the aliphatic ligand hydroxylation process. Based on the results of the kinetics and the crossover experiments, we propose a mechanism involving intramolecular C-H bond activation in a bis-μ-oxodicopper(III) type intermediate for the ligand hydroxylation reaction.

Original languageEnglish
Pages (from-to)2890-2899
Number of pages10
JournalJournal of the American Chemical Society
Issue number12
StatePublished - 1 Apr 1998


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