Mechanistic Insights into the Copper-Cocatalyzed Sonogashira Cross-Coupling Reaction: Key Role of an Anion

The Sonogashira cross-coupling reaction is one of the most important and widely used sp2–sp carbon–carbon bond formation reactions in organic synthesis. Up to now, the exact mechanism of the palladium/copper-catalyzed Sonogashira reaction is far from being fully understood, mainly due to the difficulties in clarifying the combination behavior of the two metal catalysts. In this study, DFT calculations have been performed to elucidate the mechanism of the copper-cocatalyzed Sonogashira cross-coupling reaction, where bis­(triphenylphosphino)palladium was used as a catalyst and Cs2CO3 was applied as a base. In an agreement between theory and experiment, the Cu cycle could favorably generate an I–-coordinated copper acetylide as the catalytically active species rather than the generally considered neutral copper acetylide. In addition, the transmetalation is calculated to be the rate-determining step. The results reported herein are expected to have broad mechanistic implications for other bimetal-catalyzed reactions employing metal salts as additives.