Year: 2025
Type: article
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 reported 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 operate 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 could be efficiently prepared via site-selective chlorination intermediates. Moreover, the method is readily scalable to the kilogram level. Extensive mechinistic studies were 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.
Source: Nature Communications
Authors: Yu-Qiu Guan, Tian-Zhang Wang, Muhammad Bilal, Xin-Ru Tan, Lutz Ackermann, Yu-Feng Liang
Institutions: Shandong University, University of Göttingen
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: G7100509259, G8836716975
OpenAlex ID: W4416413230