Palladium-Catalyzed Polydeuteration of (Hetero)arenes in Heavy Water Using Indazole–Pyridone Ligands

We report a Pd(II)-catalyzed C-H polydeuteration enabled by a newly designed indazole-pyridone ligand class. These ligands promote (hetero)aromatic sp² C-H perdeuteration using inexpensive D₂O as the deuterium source. Systematic studies revealed a beneficial effect of halogen substituents in the reaction system, suggesting the possible role of noncovalent interactions under aqueous conditions. The method is applicable to a range of (hetero)arenes and enables late-stage deuteration of pharmaceutically relevant molecules with high levels of deuterium incorporation.