Cooperative silver–base catalysis for multi-deuteration of heterocyclic <i>N</i>-oxides with D₂O

To address the challenges associated with the direct deuteration of quinoline, a novel synthetic strategy utilizing quinoline-<i>N</i>-oxides as starting materials has been developed. This approach enables efficient multi-deuteration of quinoline-<i>N</i>-oxides under mild conditions, employing AgOAc and triphenylphosphine as catalytic components, with D₂O as the deuterium source. The reaction demonstrates broad functional group tolerance, facilitating the deuteration of a diverse range of quinoline-, isoquinoline-, and pyridine-<i>N</i>-oxide derivatives. Mechanistic studies exclude a radical pathway and highlight the critical role of nitrogen-oxygen bonds in stabilizing key intermediates. Notably, deuteration at the C2 position is exclusively driven by K₂CO₃ as the base, while deuteration at other positions requires the cooperative action of silver salts. Furthermore, a tentative two-stage deuteration mechanism involving aryl-silver intermediates is proposed to explain the selective deuteration at other positions.