Visible-Light-Induced Deuteration of Benzylic C(sp³)─H Bonds in D₂O via Heterolytic Dissociation Mode

CD₃-containing molecules are promising as new drug candidates in the pharmaceutical industry. However, conventional synthetic routes via hydrogen isotope exchange (HIE) usually require expensive isotopic sources (D₂, DMSO-d₆, acetone-d₆), metal complex catalysts, or hazardous operations (e.g., ≥120 °C and 10 bar H₂). Here, we report a visible-light-induced deuteration strategy for benzylic C(sp³)-H bonds using a Pd/C₃N₄ photocatalyst in D₂O under 410 nm irradiation and 1 bar Ar at room temperature. The protocol enabled the late-stage benzylic deuteration of 54 alkyl(hetero)arenes (containing diverse electron-withdrawing or electron-donating groups) with excellent deuteration incorporation up to 99%, including highly functionalized natural products and pharmaceuticals. The successful gram-scale synthesis of a CD₃-containing drug (2.17 g, 10 mmol) also demonstrated the scalability and sustainability of our photo-induced approach. Mechanism studies revealed that active D species (Pd-D^δ- and N-D^δ+) from heterolytic dissociation at the interface between Pd nanoparticles and the C₃N₄ support could initiate deuteration of benzylic C(sp³)-H bonds in D₂O.