Development of Cobalt Catalysts for the <i>meta</i>-Selective C(sp²)–H Borylation of Fluorinated Arenes

Abstract

Cobalt precatalysts for the <i>meta</i>-selective borylation of fluorinated arenes are described. Initial screening and stoichiometric reactivity studies culminated in the preparation of a cobalt alkyl precatalyst supported by the sterically protected terpyridine (<b>5,5″-Me₂^<i>Ar</i>Tpy</b> = 4'-(4-<i>N,N'</i>-dimethylaminophenyl)-5,5″-dimethyl-2,2':6',2″-terpyridine). Under the optimized conditions, borylation with this precatalyst afforded up to 16 turnovers and near-exclusive <i>meta</i> regioselectivity with a range of substituted fluoroarenes in cyclopentyl methyl ether solvent at room temperature. Deuterium kinetic isotope effects of 2.9(2) at 23 °C support a turnover-limiting and selectivity-determining C(sp²)-H activation step, and stoichiometric C-H activation experiments provided insights into the identity of the C-H activating intermediate in catalysis. Analysis of the relevant Co-C and C-H bond thermodynamics support that the thermodynamics of C-H activation favor <i>ortho</i>-to-fluorine selectivity, providing additional, indirect support for kinetic control of C-H activation as the origin of <i>meta</i> selectivity.