2-Pyridone-enabled manganese-catalyzed ortho-selective deuteration of aromatic amides with D2O

Abstract

We present a highly efficient and regioselective methodology for the synthesis of ortho-deuterated aromatic amides, utilizing Mn(CO)₅Br as the catalyst, 2-pyridone as the CMD base, and D₂O as the deuterium source. This approach exhibits a broad substrate scope and exceptional functional group tolerance, enabling the late-stage deuteration of complex molecules with high yields and substantial deuterium incorporation. Mechanistic investigations suggest that 2-pyridone plays a critical role in the success of the reaction, acting as an endogenous base that facilitates reversible C–H activation and subsequent hydrogen–deuterium exchange.