Enantioselective CuII-Catalyzed Diels-Alder and Michael Addition Reactions in Water Using Bio-Inspired Triazacyclophane-Based Ligands

A triazacyclophane (TAC) scaffold decorated with three histidine amino acid residues was used as a tridentate ligand in asymmetric copper(II)-catalysed Diels-Alder and Michael addition reactions in water. Enantiomeric excesses up to 55% were obtained in Diels-Alder reactions using ligands in which the histidine residues were directly attached to the TAC scaffold. Additional amino acid residues on the N-termini of the histidine residues or positioned between the histidine residues and the TAC scaffold, resulted in almost complete loss of enantioselectivity. Modelling studies of the coordination complex of the most specific ligand indicated the presence of a substrate binding pocket in proximity to the catalytically active centre.