Scalable reductive deuteration of (Hetero)Aryl chlorides with D(2)O

利用D(2)O对(杂)芳基氯化物进行可扩展的还原氘代反应

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Abstract

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 D(2)O 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 Ni(I)/N(III) 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.

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