Organotrifluoroborate Hydrolysis: Boronic Acid Release Mechanism and an Acid-Base Paradox in Cross-Coupling

Alastair J. J. Lennox, Guy C. Lloyd-Jones

Research output: Contribution to journalArticle (Academic Journal)peer-review

138 Citations (Scopus)

Abstract

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-Miyaura coupling. The "slow. release" 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 degrees 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-base paradox assures their slow hydrolysis under basic Suzuki-Miyaura 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, beta-styryl, and anisyl moieties undergo efficient "direct" hydrolysis, resulting in fast release. Of the boronic acid While reagents bearing, for example, alkynyl or nitrophenyl moieties, hydrolyze extremely. slowly. Analysis of B-F bond lengths.(DFT) in the intermediate difluoioborane, or the Swain-Lupton resonance parameter (R) of the R group RBF3K, allows an a priori evaluation of whether an RBF3K reagent will likely engender "fast", "slow", or "very slow" hydrolysis. An exception to this correlation was found with vinyb-BF3K, this reagent being sufficiently hydrophilic to partition substantially into the predominantly aqueous minor biphase, where it is rapidly hydrolyzed.

Original languageEnglish
Pages (from-to)7431-7441
Number of pages11
JournalJournal of the American Chemical Society
Volume134
Issue number17
DOIs
Publication statusPublished - 2 May 2012

Cite this