Organotrifluoroborate Hydrolysis: Boronic Acid Release Mechanism and an Acid鈥揃ase Paradox in Cross-Coupling
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- 作者：Alastair J. J. Lennox ; Guy C. Lloyd-Jones
- 刊名：The Journal of the American Chemical Society
- 出版年：2012
- 出版时间：May 2, 2012
- 年：2012
- 卷：134
- 期：17
- 页码：7431-7441
- 全文大小：645K
- 年卷期：v.134,no.17(May 2, 2012)
- ISSN：1520-5126
文摘
The hydrolysis of potassium organotrifluoroborate (RBF3K) reagents to the corresponding boronic acids (RB(OH)2) has been studied in the context of their application in Suzuki鈥揗iyaura coupling. The 鈥渟low release鈥?strategy in such SM couplings is only viable if there is an appropriate gearing of the hydrolysis rate of the RBF3K reagent with the rate of catalytic turnover. In such cases, the boronic acid RB(OH)2 does not substantially accumulate, thereby minimizing side reactions such as oxidative homocoupling and protodeboronation. The study reveals that the hydrolysis rates (THF, H2O, Cs2CO3, 55 掳C) depend on a number of variables, resulting in complex solvolytic profiles with some RBF3K reagents. For example, those based on p-F-phenyl, naphthyl, furyl, and benzyl moieties are found to require acid catalysis for efficient hydrolysis. This acid鈥揵ase paradox assures their slow hydrolysis under basic Suzuki鈥揗iyaura coupling conditions. However, partial phase-splitting of the THF/H2O induced by the Cs2CO3, resulting in a lower pH in the bulk medium, causes the reaction vessel shape, material, size, and stirring rate to have a profound impact on the hydrolysis profile. In contrast, reagents bearing, for example, isopropyl, 尾-styryl, and anisyl moieties undergo efficient 鈥渄irect鈥?hydrolysis, resulting in fast release of the boronic acid while reagents bearing, for example, alkynyl or nitrophenyl moieties, hydrolyze extremely slowly. Analysis of B鈥揊 bond lengths (DFT) in the intermediate difluoroborane, or the Swain鈥揕upton resonance parameter () of the R group in RBF3K, allows an a priori evaluation of whether an RBF3K reagent will likely engender 鈥渇ast鈥? 鈥渟low鈥? or 鈥渧ery slow鈥?hydrolysis. An exception to this correlation was found with vinyl-BF3K, this reagent being sufficiently hydrophilic to partition substantially into the predominantly aqueous minor biphase, where it is rapidly hydrolyzed.