Insights into the synthesis and structural properties of pro-chiral 2-acetyl-N-aryl-2-(prop-2-yn-1-yl)pent-4-ynamides/-2-allyl-4-enamide derivatives through kinetics and energy frameworks

Abstract

In this study, we successfully synthesized a series of pro-chiral 2-acetyl-N-aryl-2-(prop-2-yn-1-yl)pent-4-ynamide/-2-allyl-4-enamide derivatives 5(a–n) starting from 4-enamide-N-(prop-2-yn-1-yl)pent-4-ynamide/-N-allyl-4-enamide 4 through a bimolecular nucleophilic substitution (S_N2) reaction. We report, for the first time, a novel C–C bond formation between allyl and acetoacetanilide derivatives, supported by detailed mechanistic analysis involving alkyne interactions. The reaction mechanism, characterized by a nucleophilic attack at the substrate's carbon center leading to displacement of the leaving group, was validated through intrinsic reaction coordinate (IRC) analysis, providing deeper insights into its pathway and dynamics.