• A detailed description of the reaction mechanism of AgOTf-catalyzed synthesis of 2-(3-cyclopropylisoquinolin-1-yl)-1,1-diphenylhexen-3-one using DFT calculations. • Parr function analysis showed that the generation of Ag-π complexes could influence the electrophilicity of reaction species. • During intramolecular dehydration, AgOTf acts as a dehydration medium. Lewis acid metal-catalyzed cyclizations to construct quinoline ring compounds have made breakthroughs in the more recent years. Understanding the specific mechanism of this kind of reactions remains a challenging issue in this field. In this work, the mechanism of the silver(I)-catalyzed cyclization of o-alkynylbenzaldoxime with propargyl alcohol to construct 2-(3-cyclopropylisoquinolin-1-yl)-1,1-diphenylhex-1-en-3-one was investigated using density functional theory (DFT). The calculated results indicated that the 1,3-dipole cycloaddition process is the rate-determined step of the whole reaction process. The Ag-π complex formed by AgOTf with o-alkynylbenzaldehyde oxime increased the electrophilicity of the γ-C of the alkyne group prompting the intramolecular 6-endo cyclization. In addition, the Ag-π complex formed by AgOTf with alkynyl alcohol enhances the nucleophilicity of α-C atom and the electrophilicity of β-C atom of o-alkynylbenzaldehyde oxime, thus promoting the 1,3-dipole cycloaddition reaction with isoquinoline-N-oxide. The revealed mechanism will provide valuable a clue for the design of the Ag-based novel catalyst. Abstract