An Atomically Dispersed Copper-Catalyst Lights the Way to Selective N-Demethylations.

N-demethylation is a key transformation in drug metabolism, medicinal chemistry, and late-stage amine diversification. Herein, we report a noble-metal-free, recyclable heterogeneous photocatalyst comprising atomically dispersed Cu sites on functionalized graphitic carbon nitride (Cu@f-gC3N4) for selective N-demethylation and N-dealkylation. Under 390 nm irradiation and an oxygen atmosphere, a broad range of tertiary amines, including pharmaceutically relevant substrates, are converted to secondary amines in high yields. The reaction is readily scalable to 10 mmol, and the catalyst retains its activity over more than ten reuse cycles. Atomically isolated Cu sites were confirmed by XPS, ssNMR, STEM, and EXAFS. Mechanistic studies, including radical trapping, isotope labeling, reactive oxygen species detection, kinetic analysis, in situ FTIR, and DFT calculations, support a photoredox pathway involving amine oxidation, superoxide formation, hydrogen abstraction, iminium generation, and hydrolysis, providing a structurally defined and mechanistically understood photocatalytic platform.