MECHANISTIC STUDY OF THE OXIDATIVE N-DEALKYLATION REACTIONS OF BIS(MU-OXO)DICOPPER COMPLEXES

摘要

The results of experiments designed to probe the mechanism by which the bis(mu-oxo)dicopper complexes [(LCu)(2)(mu-O)(2))](ClO4)(2) (L = 1,4,7-tribenzyl-, 1,4,7-triisopropyl-, and 1,4-diisopropyl-7-benzyl-1,4,7-triazacyclononane ligands; L(Bn3), L(iPr3), and L(iPr2Bn), respectively) decompose to products arising from macrocyclic ligand N-dealkylation are described. After removal of copper from the decomposed solutions, analysis of the organic products revealed N-dealkylated ligands and aldehyde or ketone, the oxygen atoms in the latter being derived from the bis(mu-oxo)dicopper core as shown by O-18-isotope labeling experiments. Thus, the overall N-dealkylation is akin to monooxygenase reactions carried out by various metalloenzymes such as cytochrome P450, dopamine beta-monooxygenase, and peptidyl glycine alpha-amidating monooxygenase. Direct, intramolecular attack of the bis(mu-oxo)dicopper core at a ligand substituent C-H bond during the rate-determining step was indicated by the observed first-order kinetics, the results of H/D- and O-16/O-18-isotope and double labeling experiments, large primary kinetic deuterium isotope effects (KIEs), and Eyring activation parameters. Tunneling was implicated in the C-H bond cleavage step by the temperature dependence of the KIEs. A Hammett study of the decay of suitably functionalized derivatives of L(Bn3) revealed a rho value of -0.8, consistent with the diamagnetic bis(mu-oxo)dicopper core behaving as an electrophile during C-H bond scission like the active oxidant in cytochrome P450. Subsequent hydroxyl ''rebound'' or a concerted mechanism is then proposed to generate a carbinolamine intermediate that decomposes to secondary amine and ketone or aldehyde final products.