Biomimetic O-demethylation at a copper(ii) center with imine ligand: a structural and computational study

Abstract

The catalytic cleavage of C–O bonds is a fundamental transformation in organic synthesis and biomimetic chemistry, with particular relevance to enzymatic O-demethylation. Inspired by oxidative O-demethylase enzymes, we investigated Cu(II)-mediated O-demethylation as a selective and environmentally friendly approach to breaking C–O–C bonds under mild conditions. To probe the electronic effects governing this transformation, we synthesized and characterized a series of Cu(II) complexes based on three imine ligands with varying methoxy substituent patterns. Structural and reaction studies identified key factors influencing the demethylation process, enabling a strategy for controlled O-demethylation at the Cu(II) center. Notably, exposure of complex C1 to a weakly coordinating perchlorate anion, visible light, oxygen and water induced selective demethylation of ligand L1, yielding complexes C2 and C3. X-ray crystallography confirmed the demethylated products, while spectroscopic and electrochemical analyses provided mechanistic insights. Additionally, DFT calculations elucidated the regioselectivity, demonstrating why only the methoxy group closest to the metal center undergoes cleavage. This study represents the first example of Cu(II)-mediated O-demethylation, revealing the critical interplay of electronic and geometric factors. These findings offer new perspectives for catalytic demethylation strategies and may have broader implications in sustainable lignin valorization, materials science, and environmental chemistry, showing the catalytic potential of Cu(II) ions in this reaction.