Nickel(0)-Catalyzed Denitrogenative Transannulation of Benzotriazinones with Alkynes: Mechanistic Insights of Chemical Reactivity and Regio- and Enantioselectivity from Density Functional Theory and Experiment

Abstract

The mechanism of Ni(0)-catalyzed denitrogenative transannulation of 1,2,3-benzotriazin-4(3H)-ones with alkynes to access isoquinolones has been comprehensively studied by a density functional theory (DFT) calculation and control experimental investigation. The results indicate that the transformations proceed via a sequential nitrogen extrusion, carbometalation, Ni–C bond insertion, and reductive elimination process. A frontier molecular orbital (FMO) theory and natural bond orbital (NBO) analysis reveals that the advantages of substituents on chemical reactivity and regioselectivity exist for multiple reasons: (1) Phenyl groups on the N atom of benzotriazinone and/or unsymmetrical alkynes mainly account for the high reactivity and regioselectivity via its electronic effect. (2) The π···π interaction between the phenyl substituent on the alkyne and triazole ring might partially contribute to the high regioselectivity when unsymmetrical alkynes were employed as the substrates. Furthermore, DFT calculations...