Cobalt-Catalyzed C(sp²)‑H Borylation: Mechanistic Insights Inspire Catalyst Design

A comprehensive study into the mechanism of bis­(phosphino)­pyridine (PNP) cobalt-catalyzed C–H borylation of 2,6-lutidine using B₂Pin₂ (Pin = pinacolate) has been conducted. The experimentally observed rate law, deuterium kinetic isotope effects, and identification of the catalyst resting state support turnover limiting C–H activation from a fully characterized cobalt­(I) boryl intermediate. Monitoring the catalytic reaction as a function of time revealed that borylation of the 4-position of the pincer in the cobalt catalyst was faster than arene borylation. Cyclic voltammetry established the electron withdrawing influence of 4-BPin, which slows the rate of C–H oxidative addition and hence overall catalytic turnover. This mechanistic insight inspired the next generation of 4-substituted PNP cobalt catalysts with electron donating and sterically blocking methyl and pyrrolidinyl substituents that exhibited increased activity for the C–H borylation of unactivated arenes. The rationally designed catalysts promote effective turnover with stoichiometric quantities of arene substrate and B₂Pin₂. Kinetic studies on the improved catalyst, 4-(H)₂BPin, established a change in turnover limiting step from C–H oxidative addition to C–B reductive elimination. The iridium congener of the optimized cobalt catalyst, 6-(H)₂BPin, was prepared and crystallographically characterized and proved inactive for C–H borylation, a result of the high kinetic barrier for reductive elimination from octahedral Ir­(III) complexes.