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

Abstract

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.

Concerted aryl-sulfur reductive elimination from PNP pincer-supported Co(iii) and subsequent Co(i)/Co(iii) comproportionation

“…However, outside of aryl halide coupling reactions, there have in recent years appeared examples of homogeneous catalysis by pincer-supported Co complexes where two-electron OA/RE steps are either well understood or strongly suggested. [32][33][34][35][36][37][38][39][40][41][42] In 2018, we reported on the reactivity of (POCOP) Co(Ph)(SPh). 43 In contrast to (PNP)Rh(Ph)(SPh) 18 or (POCOP) Rh(Ph)(SPh), 19 it did not undergo C-S RE but instead a RE of the phenyl with the pincer aryl (Scheme 1).…”

Dinuclear tethered pyridine, diimine complexes

“…While this manuscript was completed, Chirik et al reported on an adventitious borylation step in a PNP Co-complex. 10 The unique feature of our organo-boron compounds is the wide range of accessible products gained through C-C bond formation.…”

Insights into Activation of Cobalt Pre‐Catalysts for C(sp2)−H Functionalization

“…A sequence involving oxidative addition of a B–H or B–B followed by H–H or H–B reductive elimination, possibly involving phosphine dissociation, [11] generates the intermediate responsible for activation of the C( sp 2 )–H bond of the substrate (Schemes 2a and 2b). [5a,8,9] …”

“…Modification of the 4‐position of the pincer preceded borylation of the substrate . A cobalt(I)‐boryl compound was also identified as the C( sp 2 )−H activating species during the borylation of 5‐membered heteroarenes with HBPin but competing borylation of the cobalt pincer complex was not observed . With these heteroarenes and boron source, the catalyst resting state is the cobalt(III) complex, trans ‐( iPr PNP)Co(H) 2 BPin.…”

“…The activation mode of [( iPr PNP)Co(I)] alkyl pre‐catalysts is well understood as stoichiometric experiments have established quantitative formation of ( iPr PNP)CoBPin ( 1‐BPin ) upon treatment with either HBPin or B 2 Pin 2 . A sequence involving oxidative addition of a B−H or B−B followed by H−H or H−B reductive elimination, possibly involving phosphine dissociation, generates the intermediate responsible for activation of the C( sp 2 )−H bond of the substrate (Schemes a and 2b) ,,…”