Scalable reductive deuteration of (Hetero)Aryl chlorides with D2O

Yu-Qiu Guan, Tian-Zhang Wang, Muhammad Bilal, Xin-Ru Tan, Lutz Ackermann () and Yu-Feng Liang ()
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Yu-Qiu Guan: Shandong University, School of Chemistry and Chemical Engineering
Tian-Zhang Wang: Shandong University, School of Chemistry and Chemical Engineering
Muhammad Bilal: Shandong University, School of Chemistry and Chemical Engineering
Xin-Ru Tan: Shandong University, School of Chemistry and Chemical Engineering
Lutz Ackermann: Georg-August-Universität-Göttingen, Institut für Organische und Biomolekulare Chemie
Yu-Feng Liang: Shandong University, School of Chemistry and Chemical Engineering

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: 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 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.

Date: 2025
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DOI: 10.1038/s41467-025-66569-z

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