A dinuclear biomimetic Cu complex derived from L-histidine: synthesis and stereoselective oxidations

A dinuclear copper(II) complex derived from the chiral N-6 ligand (2S, 2' S)-N, N'-(ethane-1,2-diyl) bis(2-((1methyl-1H-imidazol-4-ylmethyl)-amino)-3-(1-trityl-1H-imidazol-4-yl) propanamide) (EHI) was synthesized and studied as a catalyst in stereoselective oxidation reactions. The ligand contains two sets of tridentate binding units, each of them giving rise to a coordination set consisting of a pair of 5-and 6-membered chelate rings, connected by an ethanediamide linker. Stereoselectivity effects were studied in the oxidations of a series of chiral (L)/(D) biogenic catechols and the pair of (L)/(D)-tyrosine methyl esters, in this case as their phenolate salts. The oxidation of beta-naphthol has also been studied as a model monooxygenase reaction. The catechol oxidation was investigated in a range of substrate concentrations at slightly acidic pH and exhibited a marked dependence on the concentration of the [Cu2EHI](4+) complex. This behavior has been interpreted in terms of an equilibrium between a monomeric and a dimeric form of the catalyst. Binding studies of (L)-and (D)-tyrosine were performed as a support for the interpretation of the stereoselectivity effects observed in the reactions. In general, [Cu2EHI](4+) exhibits a binding preference for the (L)-rather than the (D)-enantiomer of the substrates, but it appears that in the catecholase reaction the oxidation of the (D)-isomer occurs at a faster rate than for the L counterpart. The same type of enantiodiscriminating behavior is observed in the oxidation of (L)-/(D)-tyrosine methyl esters. In this case the reaction produces a complex mixture of products; the main product consisting of a trimeric compound, likely formed by radical coupling reactions, has been isolated and characterized. The oxidation of beta-naphthol yields an additional product of the expected quinone but labeling experiments with 18-O-2 show no oxygen incorporation into the product, confirming that the oxidation likely proceeds through a radical mechanism.