Synthesis of aminoboronic acids and their applications in bifunctional catalysis.

Amino acids have been known to catalyze organic reactions for many years, but their boronic acid counterparts are much less well-studied. Although there are a number of useful general approaches to the synthesis of protected aminoboronic acids, many practical challenges remain in the isolation and purification of free aminoboronic acids. Despite these issues, now several different chiral and achiral aminoboronic acids show promise as bifunctional organic catalysts. In this Account, we describe both advances in the synthesis of these aminoboronic acids and some of their underdeveloped potential in catalysis. The first aminoboronic acids that demonstrated catalytic properties, such as 8-quinoline boronic acid, enabled the hydrolysis and etherification of chlorohydrins. More recently, aminoboronic acids have effectively catalyzed direct amide formation. In addition, these catalysts can enable the kinetic resolution of racemic amines during the acylation process. Aminoboronic acids can also function as aldol catalysts, acting through in situ boronate enolate formation in water, and have facilitated tunable asymmetric aldol reactions, acting through the formation of an enamine. On the basis of these examples, we expect that these molecules can catalyze an even wider range of reactions. We anticipate many further discoveries in this area.