Role of the Base and Control of Selectivity in the Suzuki-Miyaura Cross-Coupling Reaction

• Published in: ChemCatChem 2014-05, Vol.6 (5), p.1291-1302
• Main Authors: Lima, Carlos F. R. A. C., Rodrigues, Ana S. M. C., Silva, Vera L. M., Silva, Artur M. S., Santos, Luís M. N. B. F.
• Format: Article
• Language: English
• Subjects: Acids; basicity; cross-coupling; CC coupling; organoborates; transmetalation
• ISSN: 1867-3880; 1867-3899
• DOI: 10.1002/cctc.201301080

The outcome of the Suzuki–Miyaura cross‐coupling for the direct competition reaction between two boronic acids was evaluated under routine synthesis conditions. The reaction selectivity was found to depend on the amount of the base used, with fewer bases favoring the reactivity of the boronic acid with lower pKa (stronger acid). The dependence of the reaction selectivity on base stoichiometry was found to increase with the increase in the difference in the pKa values of the competing boronic acids. These results confirm a relationship between acid–base chemistry and the Suzuki–Miyaura reaction catalytic cycle. Moreover, the results indicate that under these specific conditions, the most reactive organoboron species toward transmetalation is the borate anion RB(OH)3− instead of the neutral boronic acid RB(OH)2. Hence, the main role of the base in the reaction mechanism is to increase the reactivity of the boronic acid toward the Pd–halide complex by converting it into the respective organoborate. In addition, boric acid, an important reaction byproduct, affects the selectivity in the Suzuki reaction because its gradual formation in the reaction medium disturbs the acid–base equilibrium. Follow the organoborate road: Competition Suzuki–Miyaura reactions between two boronic acids with different pKa values reveal the link between acid–base chemistry and the reaction catalytic cycle. The results reveal that the borate path is the preferred route for transmetalation and thus confirm the role of the base in the reaction mechanism.