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 (D₂, C₂H₅OD, C₆D₆), metal complexes, or hazardous conditions (≥ 120 ^oC / 20 bar H₂). Here we demonstrate a novel synthesis route for deuterated N-heteroarenes via single-atom photocatalysis (Pd₁/TiO₂) conducted in D₂O at room temperature under 410 nm irradiation and inert atmosphere. This protocol successfully afforded satisfactory deuteration of 46 N-heteroarenes. By recycling used photocatalysts/D₂O, up to 1.157 kg (11.93 mol) deuterated N-heteroarenes (≥ 90% D incorporation) were yielded using only 4.5 L D₂O (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 D₂O described herein will offer a feasible and effective path for developing novel deuterated small-molecule drugs or electronic materials.