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

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
(k1–k5) has been developed, and together with input of [B]tot, KW, Ka,
and KaH, 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 (t0.5 > 1 week, pH 12, 70 °C). In contrast, 2-pyridyl and 5-thiazolyl
boronic acids undergo rapid protodeboronation (t0.5 ≈ 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
= pKa ± 1.6): (i) self-/autocatalysis
and (ii) sequential disproportionations of boronic acid to borinic
acid and borane.