Mechanistic Insights into the Chemo- And Regio-Selective B(C₆F₅)₃ Catalyzed C-H Functionalization of Phenols with Diazoesters

The Lewis acidic B(C₆F₅)₃ was recently demonstrated to be effective for the C-H alkylation of phenols with diazoesters. The method avoids the general hydroxyl activation in transition-metal catalysis. Ortho-selective C-H alkylation occurs regardless of potential para-selective C-H alkylation and O-H alkylation. In the present study, a theoretical calculation was carried out to elucidate the reaction mechanism and the origin of chemo- and regio-selectivity. It is found that the previously proposed B(C₆F₅)₃/N or B(C₆F₅)₃/C bonding-involved mechanisms are not favorable, and a more favored one involves the B(C₆F₅)₃/C=O bonding, rate-determining N₂ elimination, selectivity-determining electrophilic attack, and proton transfer steps. Meanwhile, the new mechanism is consistent with KIE and competition experiments. The facility of the mechanism is attributed to two factors. First, the B(C₆F₅)₃/C=O bonding reduces the steric hindrance during electrophilic attack. Second, the bonding forms the conjugated system by which the LUMO energy is reduced via the electron-withdrawing B(C₆F₅)₃. The ortho-selectivity resulted from the greater ortho-C-C (than para-C-C) interaction and the O-H···O and O-H···F hydrogen-bond interaction during electrophilic attack. The greater C-C (than C-O) interaction and the π-πstacking between the benzene rings of phenol and diazoester concerted contribute to the chemo-selective C-H alkylation.