Scalable and selective deuteration of N-heteroarenes via single-atom photocatalysis

Deuterated N -heteroarenes offer vital applications in pharmaceutical and material fields (e.g., psychotropic drugs and deuterated OLEDs) ^1,2 . However, their synthesis from hydrogen isotope exchange (HIE) reactions always requires expensive isotopic reagents (D ₂ , C ₂ H ₅ OD, C ₆ D ₆ ), metal complexes, or hazardous conditions (≥ 120 ^o C / 20 bar H ₂ ). Here we demonstrate a novel synthesis route for deuterated N -heteroarenes via single-atom photocatalysis (Pd ₁ /TiO ₂ ) conducted in D ₂ O at room temperature under 410 nm irradiation and inert atmosphere. This protocol successfully afforded satisfactory deuteration of 46 N -heteroarenes. By recycling used photocatalysts/D ₂ O, up to 1.157 kg (11.93 mol) deuterated N -heteroarenes (≥ 90% D incorporation) were yielded using only 4.5 L D ₂ O (249 mol). Mechanism investigations revealed that partially reduced single-atom Pd species, in situ generated under light irradiation, were active sites for photocatalytic HIE. The scalable and selective deuteration of N -heteroarenes via SA photocatalysis under mild conditions in D ₂ O described herein will offer a feasible and effective path for developing novel deuterated small-molecule drugs or electronic materials.