Mechanistic Studies of Cobalt-Catalyzed C(sp²)-H Borylation of Five-Membered Heteroarenes with Pinacolborane

Studies into the mechanism of cobalt-catalyzed C(sp²)-H borylation of five-membered heteroarenes with pinacolborane (HBPin) as the boron source established the catalyst resting state as the trans-cobalt(III) dihydride boryl, (^iPrPNP)Co(H)₂(BPin) (^iPrPNP = 2,6-(ⁱPr₂PCH₂)₂(C₅H₃N)), at both low and high substrate conversions. The overall first-order rate law and observation of a normal deuterium kinetic isotope effect on the borylation of benzofuran versus benzofuran-2-d₁ support H₂ reductive elimination from the cobalt(III) dihydride boryl as the turnover-limiting step. These findings stand in contrast to that established previously for the borylation of 2,6-lutidine with the same cobalt precatalyst, where borylation of the 4-position of the pincer occurred faster than the substrate turnover and arene C-H activation by a cobalt(I) boryl is turnover-limiting. Evaluation of the catalytic activity of different cobalt precursors in the C-H borylation of benzofuran with HBPin established that the ligand design principles for C-H borylation depend on the identities of both the arene and the boron reagent used: electron-donating groups improve catalytic activity of the borylation of pyridines and arenes with B₂Pin₂, whereas electron-withdrawing groups improve catalytic activity of the borylation of five-membered heteroarenes with HBPin. Catalyst deactivation by P-C bond cleavage from a cobalt(I) hydride was observed in the C-H borylation of arene substrates with C-H bonds that are less acidic than those of five-membered heteroarenes using HBPin and explains the requirement of B₂Pin₂ to achieve synthetically useful yields with these arene substrates.