Copper−Hydroperoxo-Mediated N-Debenzylation Chemistry Mimicking Aspects of Copper Monooxygenases

Abstract

A substantial oxidative N-debenzylation reaction along with PhCH═O formation occurs from a hydroperoxo−copper(II) complex that has a dibenzylamino substrate (—N(CH₂Ph)₂ appended as a substituent on one pyridyl group of its tripodal tetradentate TMPA (also TPA, (2-pyridylmethyl)amine)) ligand framework. During the course of the (L^{N(CH₂Ph)₂})Cu^II(⁻OOH) reactivity, the formation of a substrate and a ⁻OOH-derived (an oxygen atom) alkoxo Cu^II(⁻OR) complex occurs. The observation that the same Cu^II(⁻OR) species occurs from Cu^Ι/PhIO chemistry suggests the possibility that a copper−oxo (cupryl) reactive intermediate forms during the alkoxo species formation; new ESI-MS data provide further support for this high-valent intermediate. A net H atom abstraction chemistry is proposed on the basis of the kinetic isotope effect studies provided here and the previously published study for a closely related Cu^II(⁻OOH) species incorporating dimethylamine (—N(CH₃)₂) as the internal substrate;(27) the Cu^Ι/PhIO reactivity with similar isotope effect results provides further support. The reactivity of these chemical systems closely resembles the proposed oxidative N-dealkylation mechanisms that are effected by the copper monooxygenases, dopamine β-monooxygenase (DβM) and peptidylglycine-α-hydroxylating monooxygenase (PHM).