11B NMR Spectroscopy: Structural Analysis of the Acidity and Reactivity of Phenyl Boronic Acid–Diol Condensations

Phenyl boronic acids are valuable for medical diagnostics and biochemistry studies due to their ability to readily bind with carbohydrates in water. Incorporated in carbohydrates are 1,2-diols, which react with boronic acids through a reversible covalent condensation pathway. A wide variety of boronic acids have been employed for diol binding with differing substitution of the phenyl ring, with the goals of simplifying their synthesis and altering their thermodynamics of complexation. One method for monitoring their p K a ’s and binding is 11 B NMR spectroscopy. Herein, we report a comprehensive study employing 11 B NMR spectroscopy to determine the p K a of the most commonly used phenyl boronic acids and their binding with catechol or d, l -hydrobenzoin as prototypical diols. The chemical shift of the boronic acid transforming into the boronate ester was monitored at pHs ranging from 2 to 10. With each boronic acid, the results confirm (1) the necessity to use pHs above their p K a ’s to induce complexation, (2) that the p K a ’s change in the presence of diols, and (3) that 11 B NMR spectroscopy is a particularly convenient tool for monitoring these interconnected acidity and binding phenomena.