Asymmetric Sulfoxidation by a Tyrosinase Biomimetic Dicopper Complex with a Benzimidazolyl Derivative of L-Phenylalanine

A challenge in mimicking tyrosinase activity with model compounds is to reproduce its enantioselectivity. Good enantioselection requires rigidity and a chiral center close to the active site. Here, the synthesis of the new chiral copper complex, [Cu2(mXPhI)]4+/2+, based on a m-xylyl-bis(imidazole)-bis(benzimidazole) ligand containing a stereocentre with a benzyl residue directly bound on the copper chelating ring, is reported. Binding experiments show that the cooperation between the two metal centers is weak, probably due to steric hindrance given by the benzyl group. The dicopper(II) complex [Cu2(mXPhI)]4+ has catalytic activity in the oxidations of enantiomeric couples of chiral catechols with an excellent discrimination capability for Dopa-OMe enantiomers and a different substrate dependence, hyperbolic or with substrate inhibition, for the L- or D- enantiomers, respectively. [Cu2(mXPhI)]4+ is active in a tyrosinase-like sulfoxidation of organic sulfides. The monooxygenase reaction requires a reducing co-substrate (NH2OH) and yields sulfoxide with significant e.e. Experiments with 18O2 and thioanisole yielded sulfoxide with 77% incorporation of 18O, indicating a reaction occurring mostly through direct oxygen transfer from the copper active intermediate to the sulfide. This mechanism and the presence of the chiral center of the ligand in the immediate copper coordination sphere are responsible of good enantioselectivity observed.