Key mechanistic features of Ni-catalyzed C-H/C-O biaryl coupling of azoles and naphthalen-2-yl pivalates

The mechanism of the Ni-dcype-catalyzed C-H/C-O coupling of benzoxazole and naphthalen-2-yl pivalate was studied. Special attention was devoted to the base effect in the C-O oxidative addition and C-H activation steps as well as the C-H substrate effect in the C-H activation step. No base effect in the C(aryl)-O oxidative addition to Ni-dcype was found, but the nature of the base and C-H substrate plays a crucial role in the following C-H activation. In the absence of base, the azole C-H activation initiated by the C-O oxidative addition product Ni(dcype)(Naph)(PivO), 1B, proceeds via ΔG = 34.7 kcal/mol barrier. Addition of Cs₂CO₃ base to the reaction mixture forms the Ni(dcype)(Naph)[PivOCs·CsCO₃], 3-Cs-clus, cluster complex rather than undergoing PivO^- → CsCO₃^- ligand exchange. Coordination of azole to the resulting 3-Cs-clus complex forms intermediate with a weak Cs-heteroatom(azole) bond, the existence of which increases acidity of the activated C-H bond and reduces C-H activation barrier. This conclusion from computation is consistent with experiments showing that the addition of Cs₂CO₃ to the reaction mixture of 1B and benzoxazole increases yield of C-H/C-O coupling from 32% to 67% and makes the reaction faster by 3-fold. This emerging mechanistic knowledge was validated by further exploring base and C-H substrate effects via replacing Cs₂CO₃ with K₂CO₃ and benzoxazole (1a) with 1H-benzo[d]imidazole (1b) or quinazoline (1c). We proposed the modified catalytic cycle for the Ni(cod)(dcype)-catalyzed C-H/C-O coupling of benzoxazole and naphthalen-2-yl pivalate. (Chemical Equation Presented)