Alkene Borylation-Hydrogenation Enables Highly Active, Site-Selective Cobalt-Catalyzed Borylation

A method for promoting highly active and site-selective cobalt-catalyzed C(sp²)-H arene borylation is described. Addition of tert-butyl ethylene (TBE) increased the activity of the cobalt-catalyzed borylation of electron-rich arenes. With monosubstituted anisoles and anilines, synthetically useful site-selectivities favoring the meta-position of the ring were observed. Monitoring the catalytic reaction in situ by ¹H NMR spectroscopy established a borylation-hydrogenation sequence of tert-butyl ethylene as being responsible for the increased catalytic activity where borylation of the alkene preceded functionalization of the arene. Added or in situ generated trans-^tBuCH═CHBPin served as the active H₂ acceptor to overcome the inhibitory effect of HBPin and enabled both HBPin and B₂Pin₂ to be effective reagents for generating the active cobalt catalyst. Normal primary deuterium isotope effects of 5.0(1.2) and 6.0(2.0) in parallel and 3.1(1) and 3.7(3) in competition for meta and para borylation, respectively, were measured at 23 °C for the catalytic borylation of N-phenylmorpholine, supporting irreversible and rate-determining oxidative addition of the C(sp²)-H bond during the catalytic reaction. The combination of the kinetic isotope effects, in situ reaction monitoring, DFT studies, and stoichiometric experiments support the origin of meta selectivity as arising from irreversible oxidative addition of the meta-C(sp²)-H bond to cobalt(I).