Synthesis and Applications of β-Aminoalkylboronic Acid Derivatives

alpha-Aminoalkylboronic acids display a distinct role in medicinal chemistry, and their utility has been demonstrated by the successful commercialization of three drugs: bortezomib, ixazomib, and vaborbactam. Just as alpha-aminoalkylboronic acids are a bioisostere of alpha-amino acids, beta-aminoalkylboronates are a bona fide bioisostere of beta-amino acids, thus they also hold promising potential in drug discovery. Moreover, beta-aminoalkylboronates are versatile synthetic intermediates that are amenable to many of the established C-B bond derivatization reactions of chiral optically enriched alkylboronates, leading to the stereocontrolled preparation of valued classes of products such as beta-amino alcohols, 1,2-diamines, and hemiboronic acid heterocycles. In addition, beta-aminoalkylboronates were shown to act as catalysts in certain organic reactions. This review presents an overview of the strengths and limitations of current preparative methods to access beta-aminoalkylboronic acid derivatives stereoselectively with various substitution patterns. Strategically, several disconnections can be exploited to establish both functional groups. Some of the key methods include the classical Matteson asymmetric homologation chemistry, transition metal-catalyzed aminoboration of alkenes and formal hydroboration of enamine derivatives, nucleophilic additions of boryl-substituted carbanions ontoN-functionalized imines, borylative ring openings of aziridines, and functionalization of alpha-boryl aldehydes.

Automated summary

This review highlights the significance of alpha-aminoalkylboronic acids and beta-aminoalkylboronates in medicinal chemistry, and explores their potential as bioisosteres of amino acids. It also discusses the versatile synthetic intermediates of beta-aminoalkylboronates and their role as catalysts in organic reactions.