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

• Published in: Journal of the American Chemical Society Vol. 138; no. 29; pp. 9145 - 9157
• Main Authors: Cox, Paul A, Leach, Andrew G, Campbell, Andrew D, Lloyd-Jones, Guy C
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 27-07-2016
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.6b03283

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 °C). In contrast, 2-pyridyl and 5-thiazolyl boronic acids undergo rapid protodeboronation (t 0.5 ≈ 25–50 s, pH 7, 70 °C), 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.