Unveiling the Novel Mechanistic Insights and Role of Base in Zn‐Catalyzed Csp–Csp² Cross‐Coupling Reaction

ABSTRACT A detailed mechanistic investigation of the Zn (II)‐catalyzed Csp–Csp 2 (Sonogashira‐type) cross‐coupling reaction is reported herein, using the Density Functional Theory method. The present study unveiled an unconventional non‐redox mechanism for Zn‐catalyzed cross‐coupling reaction, where the oxidation state of Zn remains intact throughout the catalytic cycle. Our study further revealed the significant role of the base in controlling the feasibility of cross‐coupling reactions that are catalyzed by electron‐deficient metal centers. Our study indicates that K 3 PO 4 acts as an ancillary ligand (Lewis base) for the electron‐deficient Zn (II) catalytic center rather than as a proton abstractor for the nucleophilic coupling partner (phenylacetylene) in this reaction. The active catalyst was identified to be a four‐coordinate bis‐DMEDA Zn (II) complex. The mechanism proceeds via the initial activation of the nucleophilic coupling partner (phenylacetylene), followed by the electrophilic coupling partner (organic halide) activation liberating the cross‐coupled product by a concerted nucleophilic substitution pathway. The turn‐over limiting step was identified to be the activation of the electrophilic coupling partner. The activation barrier obtained for the reaction, 31.0 kcal/mol concords well with experimental temperature requirements (125°C). The coordination by base is found to stabilize the rate‐determining intermediates and transition states involved in the reaction. The mechanistic insights gained from this study could aid in the rational design and development of sustainable cross‐coupling reactions using zinc as the catalyst.