Brønsted Acid and H-Bond Activation in Boronic Acid Catalysis.

Boronic acid catalysis has emerged as a mild method for promoting a wide variety of reactions. It has been proposed that the mode of catalysis involves Lewis acid or covalent activation of hydroxyl groups by boron, but limited mechanistic evidence exists. In this work, representative boronic acid catalyzed reactions of alcohols and oximes have been reinvestigated. A series of control experiments with boronic and Brønsted acids were interpreted along with correlations between their reactivity and their acidity measured by the Gutmann-Beckett method. Overall, it was concluded that the major modes of catalysis involve either dual H-bond catalysis or Brønsted acid catalysis. Strong Brønsted acids were shown to be generated in situ from covalent assembly of the boronic acids with hexafluoroisopropanol, explaining why the solvent had such a major impact on the reactivity. This new insight should guide the future development of boronic acid catalysis, where the diverse and solvent-specific nature of catalytic modes has been overlooked.