Computational study of regiodivergent pathways in the copper-catalyzed borocyanation of 1,3-dienes: Mechanism and origin of regioselectivity

Abstract Regioselective control in the Cu-catalyzed borylcyanation of nonsymmetrically substituted 1,3-dienes remains challenging. In this study, we used density functional theory calculations to elucidate the origins of ligand- and substrate-controlled regioselectivity. The mechanism rationalizes why ligand PCy3 favors 1,2-borocupration while ligand XantPhos favors 4,3-borocupration for 2-substituted 1,3-dienes, and why 1-substituted, 1,2-disubstituted, and 1,3-disubstituted 1,3-dienes afford 4,3-borocupration, irrespective of the presence of bidentate or monodentate ligands. Based on established experiments and stimulated by other relevant reactions, we attempted to enrich ligands and substrates computationally. The different regioselectivities for different substrates and ligands were attributed to different electronic and steric factors.