Heterolytic bond dissociation energy related to C−F activation in nickel-catalyzed cross-coupling of phenylmagnesium chloride with fluoroarenes

The activation of the C−F bond remains extremely challenging in organic synthesis due to its inherent inertness compared to other carbon-halogen bonds. Herein, a mechanistic study is described of the nickel-catalyzed cross-coupling of phenylmagnesium chloride with 4-fluoroanisole by the aid of density functional theory (DFT) calculations. The computations show that aryl C−F bond activation is assisted by the cooperative catalysis of nucleophilic nickel bridged by the deprotonated air-stable secondary phosphine oxide (SPO) ligand, along with Lewis acidic magnesium. Compared to the cleavage of C−O bond, this unusual chemoselective activation of C−F bond is controlled by heterolytic bond dissociation energy (HBDE). A linear free energy relationship (LFER) between fluoroarenes' HBDE and C−F activation energy barriers was established, further confirming that HBDE plays a significant role in the activation of aryl C−F bonds.