Unveiling the origin of the chemoselectivity of bismacycle-mediated C–H arylation of phenols: from mechanism concept to new coupling design

Abstract

Recently, a bismacycle-mediated functionalization was presented by Ball and co-workers as an elegant strategy to perform the C–H arylation of phenols. Through density functional theory calculations, we have performed a thorough study on the mechanism, selectivity, and electronic nature. Firstly, the reaction was initiated by the oxidative addition (OA) of aryl bismacycle by mCPBA, which occurs through a stepwise mechanism, in which a rate-determining oxo-transfer is followed by the barrierless addition of mCBA. The resulting hexacoordinated Bi(V) intermediate subsequently undergoes a rapid ligand exchange (LE) with phenol, followed by a fast reductive elimination (RE) to give the C–C bond formation product. Secondly, by exploring the chemoselectivity for C–O versus C–C arylation, we showed that the C–O bond RE leading to diphenylether exhibited a significantly higher barrier than the o-arylated RE by 4.3 kcal mol⁻¹, in sharp contrast to the unselective coupling with BiPh₃Cl₂ previously reported by Barton. The difference in chemoselectivity originates from a switch in the RE mechanism according to whether a LE with phenol occurs prior to the Bi(V)/Bi(III) RE step. Under Ball's conditions, the stronger basicity of the hydroxide ligand ensures a fast LE to give the hexacoordinated Bi–OAr intermediate that strongly favours the C–C bond formation, whereas in Barton's work LE could not occur and RE had to follow a concerted intramolecular proton-transfer mechanism for which the chemoselectivity was low (0.8 kcal mol⁻¹). Thirdly, the effect of substitute groups and then the nature of RE are studied using Hammett analysis, atomic charge analysis, and designed reaction modes, which all revealed that C–C RE from Bi(V) is polar. Finally, new Bi(III)/Bi(V) cross-coupling modes such as aryl–enolate and alkene–enolate couplings were designed and have shown substantially reduced RE barriers for C–C bond formation and remarkably increased chemoselective preference.