The Suzuki-Miyaura Coupling (SMC) reaction is a powerful method for forming carbon-carbon bonds in organic synthesis. Recent advancements in SMC reactions have introduced first-row transition metal catalysts, with zinc garnering significant interest due to its cost-effective and eco-friendly nature. Despite progress in experimental protocols, the mechanistic details of zinc-catalyzed SMC reactions are limited. This study explores the mechanism of Zn-catalyzed SMC reactions between alkynyl halides and aryl boronic acids using density functional theory. A four-coordinated DMEDA ligated Zn(II) complex is identified as the active catalyst. Unlike Pd-catalyzed SMC, the mechanism proceeds via an initial transmetalation process forming aryl zincates. Further, the activation of organic halide occurs through a redox-neutral pathway involving a concerted nucleophilic substitution-reductive elimination process, eliminating the cross-coupled product while regenerating the active catalyst. The energy span (27.2kcal/mol) for the process concords with the temperature requirements (80oC) in the experiment. The activation of organic halide is identified as the turnover-limiting step. The unconventional redox-neutral mechanism could be rationalized by the stable d10 configuration at the Zn(II) center and the ease of bond-formation between the coupling partners. This computational study thereby provides new mechanistic insights into Suzuki cross-coupling reactions, aiding the synthesis of novel functional scaffolds using eco-friendly methods.

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