Switchable electroreductive C3 or C3,C5 deuteration of imidazo[1,2-a]pyridines

Abstract

A practical and scalable electrochemical protocol has been developed for the regioselective deuteration of imidazo[1,2-a]pyridines using D₂O as the deuterium source. This transition-metal-free strategy enables selective C3 or C3,C5 deuteration under mild conditions, with the regioselectivity controlled by the choice of electrode materials and supporting electrolyte. The method demonstrates broad substrate scope, high deuterium incorporation, and excellent functional group tolerance. Notably, deuterated imidazopyridine-based pharmaceuticals, including zolimidine-d₂, necopidem-d₁, and saripidem-d₁ were selectively synthesized using this approach. A plausible reaction mechanism is proposed based on control experiments and cyclic voltammetry studies.