Fundamental Study on the Reactivity of 4-Pyridylboronic Acid Derivatives with Strong Acidities

The acid dissociation constants (K_a) of 4-pyridylboronic acid derivatives were determined spectrophotometrically, and the pK_aassignment was performed based on ¹¹B NMR spectroscopy. It was found that both of the boron centers in 4-pyridylboronic acid (4-PyB(OH₂) and the N-methylated derivative [4-(N-Me)Py⁺B(OH)₂] have strong acidities (pK_a^B= 4.00 and 3.96, respectively), indicating that the introduction of a methyl group into the nitrogen atom of the pyridine ring in 4-pyridylboronic acid has no influence on the acidity of the boron center. Kinetic studies on the complexation reactions of 4-(N-X)Py⁺B(OH)₂(X = H, Me) with hinokitiol (Hipt) were carried out under pseudo first-order conditions, where the total concentration of boronic acid was much larger than that of Hipt. Both 4-HPy⁺B(OH)₂and 4-(N-Me)Py⁺B(OH)₂reacted with Hipt much faster than their conjugate boronate ions (4-HPy⁺B(OH)₃^-and 4-(N-X)Py⁺B(OH)₃^-, respectively), which is consistent with our recent results. The rate constants (k₁) for the reactions of the boronic acids with Hipt increase with an increase of the acidity of boronic acid. The reactivity of 4-(N-Me)Py⁺B(OH)₂, having the strongest acidity (pK_a^B= 3.96), was still higher than the phenyl and pyridyl boronic acid derivatives having pK_a^B= /4.40 - 10.74, which we have examined so far.