Scalable reductive deuteration of (Hetero)Aryl chlorides with D2O

Deuterated compounds serve as powerful tools for investigating reaction mechanisms, tracing molecular pathways, as well as enhancing properties in medicinal and materials science. Herein, we report a nickel-catalyzed deutero-dehalogenation of abundant yet inert aryl chlorides, enabling direct access to deuterated (hetero)arenes using D2O as the exclusive, economical deuterium source. This reductive cross-coupling strategy overcomes traditional limitations of aryl chlorides and operates under mild conditions. This protocol delivers products with a high degree of deuterium incorporation across a broad range of (hetero)aryl substrates. It also exhibits excellent functional group tolerance and tolerates various sensitive functional groups including anilines, phenols, and organoboron derivatives. A variety of deuterated products have been efficiently prepared via site-selective chlorination intermediates. Moreover, the method is readily scalable to the kilogram level. Extensive mechanistic studies have been carried out to provide insights into the non-radical NiI/NIII catalytic cycle. The simplicity, cost-effectiveness, and scalability of this approach make it highly attractive for applications in drug discovery, mechanistic studies, and metabolic research. Deuterated compounds serve as powerful tools for investigating reaction mechanisms, tracing molecular pathways, as well as enhancing properties in medicinal and materials science. Herein, the authors report a nickel-catalyzed deutero-dehalogenation of abundant yet inert aryl chlorides, enabling direct access to deuterated (hetero)arenes using D2O as the deuterium source.