Theoretical Insights Into the Molecular Mechanism of Fe Catalysed Sonogashira Cross-Coupling Reaction

Abstract

The Sonogashira type cross-coupling reaction constitutes a pivotal method for constructing C(sp${}^2$)–C(sp) bonds, enabling the synthesis of structurally diverse aryl alkynes with broad applications in pharmaceuticals and materials science. In the present study, a comprehensive mechanistic investigation of the iron-catalysed Sonogashira-type coupling between phenylacetylene and 4-iodoacetophenone was performed employing density functional theory (DFT) calculations. The catalytic system, comprising FeCl${}_3·$6H${}_2$O and 1,10-phenanthroline in aqueous medium under aerobic conditions, was examined in detail. Our results elucidate a mechanistic pathway that proceeds via an initial formation of the pre-catalytic species through an interaction between the metal iron and the ligand phenanthroline, followed by base-assisted activation of the terminal alkyne to form the active catalytic species, culminating in C–C bond formation through a concerted nucleophilic substitution process. This study reveals a feasible redox-neutral mechanistic pathway where the iron centre remains in its +3 oxidation state throughout the reaction cycle and thereby provides valuable insights into the reactivity of the iron-catalysed Sonogashira coupling reaction.