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Organoboron Reagent-Controlled Selective (Deutero)Hydrodefluorination |
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| Authors: | Zheng-Jia Shen Dr. Chen Zhu Xiao Zhang Prof. Dr. Chao Yang Prof. Dr. Magnus Rueping Prof. Dr. Lin Guo Prof. Dr. Wujiong Xia |
| Affiliation: | 1. State Key Lab of Urban Water Resource and Environment, School of Science, Harbin Institute of Technology (Shenzhen), Shenzhen, 518055 China These authors contributed equally to this work.;2. KAUST Catalysis Center (KCC), King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900 Saudi Arabia These authors contributed equally to this work.;3. State Key Lab of Urban Water Resource and Environment, School of Science, Harbin Institute of Technology (Shenzhen), Shenzhen, 518055 China;4. KAUST Catalysis Center (KCC), King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900 Saudi Arabia |
| 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. |
| Keywords: | C−F Bond Cleavage Electrolysis Hydrodefluorination Organoboron Trifluoroacetamide |