Cobalt-Catalyzed Borylation Of Fluorinated Arenes: Thermodynamic Control Of C(Sp(2))-H Oxidative Addition Results In Ortho-To-Fluorine Selectivity

The mechanism of C(sp(2))-H borylation of fluorinated arenes with B(2)Pin(2) (Pin = pinacolato) catalyzed by bis(phosphino)pyridine ((PNP)-P-iPr) cobalt complexes was studied to understand the origins of the uniquely high ortho-to-fluorine regioselectivity observed in these reactions. Variable time normalization analysis (VTNA) of reaction time courses and deuterium kinetic isotope effect measurements established a kinetic regime wherein C(sp(2))-H oxidative addition is fast and reversible. Monitoring the reaction by in situ NMR spectroscopy revealed the intermediacy of a cobalt(I)-aryl complex that was generated with the same high ortho-to-fluorine regioselectivity associated with the overall catalytic transformation. Deuterium labeling experiments and stoichiometric studies established C(sp(2))-H oxidative addition of the fluorinated arene as the selectivity-determining step of the reaction. This step favors the formation of ortho-fluoroaryl cobalt intermediates due to the ortho fluorine effect, a phenomenon whereby ortho fluorine substituents stabilize transition metal-carbon bonds. Computational studies provided evidence that the cobalt-carbon bonds of the relevant intermediates in ((PNP)-P-iPr)Co-catalyzed borylation are strengthened with increasing ortho fluorine substitution. The atypical kinetic regime involving fast and reversible C(sp(2))-H oxidative addition in combination with the thermodynamic preference for forming cobalt-aryl bonds adjacent to fluorinated sites are the origin of the high regioselectivity in the catalytic borylation reaction.