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Role of the Base and Control of Selectivity in the Suzuki–Miyaura Cross‐Coupling Reaction
Author(s) -
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.
Publication year - 2014
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201301080
Subject(s) - boronic acid , chemistry , transmetalation , selectivity , reactivity (psychology) , boric acid , catalysis , coupling reaction , suzuki reaction , phenylboronic acid , base (topology) , combinatorial chemistry , organic chemistry , medicinal chemistry , palladium , medicine , alternative medicine , pathology , mathematical analysis , mathematics
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 p K a (stronger acid). The dependence of the reaction selectivity on base stoichiometry was found to increase with the increase in the difference in the p K a 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 RB(OH) 3 − instead of the neutral boronic acid RB(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.