Protodeboronation of Heteroaromatic, Vinyl, and Cyclopropyl Boronic Acids: pH-Rate Profiles, Autocatalysis, and Disproportionation

摘要

pH-rate profiles for aqueous-organic protodeboronation of 18 boronic acids, many widely viewed as unstable, have been studied by NMR and DFT. Rates were pH-dependent, and varied substantially between the boronic acids, with rate maxima that varied over 6 orders of magnitude. A mechanistic model containing five general pathways (k_1-k_5) has been developed, and together with input of [B]_(tot), K_W, K_a, and K_(aH), the protodeboronation kinetics can be correlated as a function of pH (1-13) for all 18 species. Cyclopropyl and vinyl boronic acids undergo very slow protodeboronation, as do 3- and 4-pyridyl boronic acids (t_(0.5) ＞ 1 week, pH 12, 70 ℃). In contrast, 2-pyridyl and 5-thiazolyl boronic acids undergo rapid protodeboronation (t_(0.5) ≈ 25-50 s, pH 7, 70 ℃), via fragmentation of zwitterionic intermediates. Lewis acid additives (e.g., Cu, Zn salts) can attenuate (2-pyridyl) or accelerate (5-thiazolyl and 5-pyrazolyl) fragmentation. Two additional processes compete when the boronic acid and the boronate are present in sufficient proportions (pH = pK_a ± 1.6): (ⅰ) self-/autocatalysis and (ⅱ) sequential disproportionations of boronic acid to borinic acid and borane.