Computational Study on a Copper‐Catalyzed Atroposelective Dehydro‐Diels–Alder Reaction of Ynamide via Vinyl Cation: Mechanistic Investigations and Chiral Induction Model

Abstract Dehydro‐Diels–Alder (DDA) reaction serves as one of the most prominent methods for the synthesis of aromatic compounds. Herein, our study elucidates the mechanism and origin of atroposelectivity of Cu(I)‐catalyzed DDA reactions of aryl‐substituted 1,6‐diyne substrate via density functional theory calculations. The intramolecular nucleophilic cyclization is identified as the rate‐ and stereo‐determining step, with a 2.3 kcal/mol free energy difference between the two atropo‐determining transition states. Chiral induction arises from a global–local synergy: the chiral ligand's bulky side arms shape the topological portrait of the catalytic pocket, restricting substrate orientation, while local π‐π interactions stabilize the transition state leading to the major product. Absence of the bulky side arms diminishes the atropo‐selectivity ( G ‡ = 0.1 kcal/mol), thus validating our chiral induction model. This work highlights the critical role of microenvironments within catalytic pocket in asymmetric catalysis and provides insights for designing new catalysts.