(bpy)Cu(CF3)3: tunable reactivity in fluoroalkylation and fluorination
Min Xu1, Shuolu Dai1, Shan Long1
1State Key Laboratory of Green Pesticide, Center for R&D of Fine Chemicals of Guizhou University, Guizhou University, Guiyang 550025, China. wxlv@gzu.edu.cn.
Abstract:
Organofluorine compounds play an indispensable role in modern pharmaceuticals, agrochemicals, and functional materials. Fluorine-containing groups such as trifluoromethyl (CF3) and difluoromethoxy (OCF2H) can significantly enhance lipophilicity, metabolic stability, hydrogen-bonding capability, and target-binding affinity, thereby serving as key structural units in drug design and activity optimization. Among various trifluoromethylation strategies, (bpy)Cu(CF3)3-an isolable and storable high-valent Cu-CF3 species-exhibits tunable reactivity that enables direct trifluoromethylation, defluorinative difluoromethylation, and P-F bond formation (fluorination). This review systematically summarizes recent advances in the application of (bpy)Cu(CF3)3 to fluorination and fluoroalkylation reactions and classifies these reactions into three mechanistic pathways: two-electron, single-electron radical, and difluorocarbene/fluoride pathways. The reaction mechanisms, structural characteristics, substrate scope, and synthetic applications are discussed in detail. Finally, current challenges and future opportunities in this field are discussed, aiming to provide guidance for the design of next-generation multifunctional fluorinating reagents and for the further development of organofluorine chemistry.
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