Organoboron Reagent-Controlled Selective (Deutero)Hydrodefluorination

Zheng-Jia Shen, Chen Zhu, Xiao Zhang, Chao Yang, Magnus Rueping, Lin Guo, Wujiong Xia

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

(deuterium-labeled) CF2H- and CFH2-moieties are of high interest in drug discovery. The high demand for the incorporation of these fluoroalkyl moieties into molecular structures has witnessed significant synthetic progress, particularly in the (deutero)hydrodefluorination of CF3-containing compounds. However, the controllable replacement of fluorine atoms while maintaining high chemoselectivity remains challenging. Herein, we describe the development of a selective (deutero)hydrodefluorination reaction via electrolysis. The reaction exhibits a remarkable chemoselectivity control, which is enabled by the addition of different organoboron sources. The procedure is operationally simple and scalable, and provides access in one step to high-value building blocks for application in medicinal chemistry. Furthermore, density functional theory (DFT) calculations have been carried out to investigate the reaction mechanism and to rationalize the chemoselectivity observed.
Original languageEnglish (US)
JournalAngewandte Chemie International Edition
DOIs
StatePublished - Dec 16 2022

Bibliographical note

KAUST Repository Item: Exported on 2022-12-19
Acknowledgements: We are grateful for the financial support from the National Natural Science Foundation of China (No.22101066), the Science and Technology Plan of Shenzhen (No. JCYJ20210324133001004and JCYJ20210324132803009), the Natural Science Foundation of Guangdong (No. 2020A1515010564 and 2022A1515010863), and Guangdong Basic and Applied Basic Research Foundation (No. 2021A1515220069). W. X. is grateful for the Talent Plan of the Pearl River in Guangdong, Starting up fund from the Shenzhen Government, and the financial support from Guangdong Province Covid-19 Pandemic Control Research Fund (no. 2020KZDZX1218). C. Z. thanks the KAUST Supercomputing Laboratory for providing the computational resources of the Shaheen-II supercomputer. The project was also supported by State Key Laboratory of Urban Water Resource and Environment (Harbin Institute of Technology) (No.2022TS23), and the Open Research Fund of the School of Chemistry and Chemical Engineering, Henan Normal University.

ASJC Scopus subject areas

  • General Chemistry
  • Catalysis

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