Nickel-Catalyzed Selective Defluorinative Deuteration of Polyfluoroarenes
Zhi Liu1, Xiaoyu Zhang1, Xiaoliang Yang1
1State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing Drum Tower Hospital, Jiangsu Key Laboratory of Advanced Organic Materials, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing 210023, China.
Journal of the American Chemical Society
|April 27, 2026
Summary
Researchers developed a new nickel-catalyzed method for precise deuterium labeling in organic synthesis. This technique allows controlled incorporation of deuterium into polyfluoroarenes, aiding drug discovery and ADME studies.
Area of Science:
- Organic Synthesis
- Medicinal Chemistry
- Catalysis
Background:
- Deuterium-labeled compounds are crucial for drug discovery and ADME studies.
- Achieving precise control over deuterium incorporation sites and levels in organic synthesis is difficult.
Purpose of the Study:
- To develop a novel method for selective and programmable deuterium labeling of polyfluoroarenes.
- To establish polyfluoroarenes as versatile precursors for synthesizing deuterium-enriched compounds.
Main Methods:
- Nickel-catalyzed defluorinative deuteration of polyfluoroarenes.
- Utilizing methanol-d (MeOD) as a deuterium source.
- Investigating the cooperative effects of lithium and zinc salts in C-F bond activation.
Main Results:
- Highly selective deuteration at carbon-fluorine (C-F) bond sites.
- Programmable installation of one to four deuterium atoms.
- Demonstrated cooperative effects of Li and Zn salts for improved reactivity and selectivity.
Conclusions:
- Established a new synthetic platform for selective synthesis of multideuterated compounds.
- Polyfluoroarenes are now versatile feedstocks for precision deuterium labeling.
- Facilitates the synthesis of deuterium-enriched fluoroarenes for drug development and metabolic research.
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