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

The Sonogashira type cross‐coupling reaction constitutes a pivotal method for constructing C(sp)–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 FeCl6HO 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.