A dinuclear biomimetic Cu complex derived from l-histidine: synthesis and stereoselective oxidations. Issue 12 (8th March 2017) - Perrone, Maria L.
Abstract : A new dicopper(ii ) complex with a histidine-derived N6 ligand performs a biomimetic stereoselective oxidation of catechols. Abstract : A dinuclear copper(ii ) complex derived from the chiral N6 ligand (2 S, 2′ S )- N, N ′-(ethane-1, 2-diyl)bis(2-((1-methyl-1 H -imidazol-4-ylmethyl)-amino)-3-(1-trityl-1 H -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 chirall /d biogenic catechols and the pair ofl /d -tyrosine methyl esters, in this case as their phenolate salts. The oxidation of β-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 [Cu2 EHI] 4+ complex. This behavior has been interpreted in terms of an equilibrium between a monomeric and a dimeric form of the catalyst. Binding studies ofl - andd -tyrosine were performed as a support for the interpretation of the stereoselectivity effects observed in the reactions. In general, [Cu2 EHI] 4+ exhibits a binding preference for thel - rather than thed -enantiomer of the substrates, but it appears that in the catecholase reaction the oxidation of thed -isomer occurs at a faster rate than for thel counterpart. The same type of enantio-discriminating behavior is observed in the oxidation ofl -/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 β-naphthol yields an additional product of the expected quinone but labeling experiments with 18-O2 show no oxygen incorporation into the product, confirming that the oxidation likely proceeds through a radical mechanism.