Cu-Catalyzed Direct C–H Alkylation of Polyfluoroarenes via Remote C(sp<sup>3</sup>)–H Functionalization in Carboxamides
Hongchao Liu, Yuke Li, Xiao-Ping Gong, Zhi‐Jie Niu, Yu‐Zhao Wang, Ming Li, Wei‐Yu Shi, Zhe Zhang, Yong‐Min Liang
Abstract
A novel dehydrogenative coupling reaction of N-fluorocarboxamides with polyfluoroarenes forming C(sp2)–C(sp3) bonds enabled by copper catalysis has been accomplished. N-Fluorocarboxamides are postulated to undergo copper-mediated dehydrogenative cross-coupling reaction with electron-deficient polyfluoroarenes via a radical pathway. Benzylic C–H bonds and aliphatic C–H bonds in N-fluorocarboxamides could proceed smoothly and demonstrated excellent regioselectivity. The detailed mechanism presented is supported by control experiments and density functional theory calculations.
Topics & Concepts
ChemistryRegioselectivityCatalysisSurface modificationAlkylationDensity functional theoryCombinatorial chemistryCopperMedicinal chemistryComputational chemistryStereochemistryOrganic chemistryPhysical chemistryCatalytic C–H Functionalization MethodsFluorine in Organic ChemistryRadical Photochemical Reactions