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.