Mechanistic Study of Chemoselectivity in Ni-Catalyzed Coupling Reactions between Azoles and Aryl Carboxylates

Itami et al. recently reported the C–O electrophile-controlled chemoselectivity of Ni-catalyzed coupling reactions between azoles and esters: the decarbonylative C–H coupling product was generated with the aryl ester substrates, while C–H/C–O coupling product was generated with the phenol derivative substrates (such as phenyl pivalate). With the aid of DFT calculations (M06L/6-311+G­(2d,p)-SDD//B3LYP/6-31G­(d)-LANL2DZ), the present study systematically investigated the mechanism of the aforementioned chemoselective reactions. The decarbonylative C–H coupling mechanism involves oxidative addition of C­(acyl)–O bond, base-promoted C–H activation of azole, CO migration, and reductive elimination steps (C–H/Decar mechanism). This mechanism is partially different from Itami’s previous proposal (Decar/C–H mechanism) because the C–H activation step is unlikely to occur after the CO migration step. Meanwhile, C–H/C–O coupling reaction proceeds through oxidative addition of C­(phenyl)–O bond, base-promoted C–H activation, and reductive elimination steps. It was found that the C–O electrophile significantly influences the overall energy demand of the decarbonylative C–H coupling mechanism, because the rate-determining step (i.e., CO migration) is sensitive to the steric effect of the acyl substituent. In contrast, in the C–H/C–O coupling mechanism, the release of the carboxylates occurs before the rate-determining step (i.e., base-promoted C–H activation), and thus the overall energy demand is almost independent of the acyl substituent. Accordingly, the decarbonylative C–H coupling product is favored for less-bulky group substituted C–O electrophiles (such as aryl ester), while C–H/C–O coupling product is predominant for bulky group substituted C–O electrophiles (such as phenyl pivalate)