Mechanism and Origins of Regioselectivity of Copper-Catalyzed Borocyanation of 2-Aryl-Substituted 1,3-Dienes: A Computational Study.

Density functional theory calculations were performed to investigate the copper-catalyzed borocyanation of 2-aryl-substituted 1,3-dienes. The computations show that the regioselectivity of the overall reaction is governed by the combination of the inherent regioselectivity of the borocupration and electrophilic cyanation steps. The π-conjugation effect of the 1,3-diene makes the terminal carbon atoms more electrophilic compared with the internal carbon atoms, which coupled with the steric effect results in the 4,3- and 1,2-borocupration being intrinsically more favorable than the other possibilities. The steric repulsion around the breaking Cu-C bond was found to be the key factor in determining the regioselectivity of the electrophilic cyanation. The origins of the experimentally observed ligand-controlled regioselectivity were ascribed to the electronic and steric effects. For the bulky XantPhos ligand, the 4,3-borocupration was found to be more favorable than the 1,2-borocupration due to the steric repulsion around the forming Cu-C bond, resulting in the formation of the 4,3-borocyantion product. On the other hand, the reversed regioselectivity with a small PCy ligand is mainly caused by the electronic effect that the π-electron-withdrawing aryl group at the C atom makes the C atom more electrophilic than the C atom, enabling the 1,2-borocupration to be more favorable than the 4,3-borocupration.