54. Mechanistic insights into the Chemo- and Regio-selective B(C6F5)3 Catalyzed C-H Functionalization of Phenols with Diazoesters

Zhang, Q.; Zhang, X.; Li, M.; Li, C.; Liu, J.-Q.;* Jiang, Y.-Y.;* Ji, X.; Liu, L.; Wu, Y.-C.  J. Org. Chem. 2019, 84, 14508-14519. Download Link

Abstract: 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, ratedetermining 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−π stacking between the benzene rings of phenol and diazoester concerted contribute to the chemo-selective C−H alkylation.