Mechanism Of Suzuki-Miyaura Coupling Revealed

Trifluoroborate reagents are widely used as higher-yielding alternatives to traditional boronic acids in Suzuki-Miyaura coupling reactions, the palladium-catalyzed union of organoboron compounds with organohalides. But the mechanism of the tri­fluo­roborate-based reactions (such as the one shown) has not been well understood. Now, Guy C. Lloyd-Jones of the University of Bristol, in England, and coworkers report using NMR, kinetics, isotopic labeling, and computation to investigate the mechanism (Angew. Chem. Int. Ed., DOI: 10.1002/anie.201001522). The study comes to a surprising conclusion—that trifluoroborates are hydrolyzed in the reactions to liberate the same boronic acids they were supposed to have replaced. Lloyd-Jones and colleagues show how several key mechanistic processes that result from trifluoroborate hydrolysis account for the reactions’ high efficiency, and they point out that these principles can now be used to optimize these and other reactions. For example, they note that boronic acid can couple with equally high efficiency as trifluoroborate if it is introduced into the reaction mixture in a slow and deliberate manner.