Photochromic Cu-TiO₂ Nanocatalysts for Visible-Light-Triggered C-Cl Activation and Selective Molecular Assembly

The efficient photoactivation of C-Cl bonds to selectively form C-C and C-O bonds via cross-coupling has emerged as a promising strategy for photosynthesizing pharmaceuticals. However, achieving selective cross-coupling of unactivated C-Cl bonds using visible light in a photoredox system remains a formidable challenge. Herein, we report a cooperative photoredox catalysis system that efficiently activates benzyl chloride (BnCl) in conjunction with photooxidation of hydroxyphenol, enabling the selective formation of C-C and C-O pharmaceuticals, such as 4-(benzyloxy)phenol (monobenzone) and benzylated 1,4-benzoquinone, over photochromic Cu-doped TiO₂ (Cu-TiO₂) nanoparticles. Mechanistic investigations and theoretical calculations reveal that the Cu doping enhances the BnCl coordination, and the photochromism-induced Cu^+/0 active sites efficiently promote the C-Cl bonds activation, resulting in homocoupling of bibenzyl with excellent yield (>96%), selectivity (>99%), and stability (>30 days). Moreover, C-C and C-O bond pharmaceuticals are selectively synthesized by cooperating the photoreduction of BnCl with the solvent-induced photooxidation of p-phenol, facilitated by photochromism-induced Cu^+/0 species and oxygen vacancies in Cu-TiO₂ nanoparticles. This work establishes a framework for the rational design of photochromic catalysts for the activation and functionalization of C/Cl bonds within a photoredox system.