Benzoxaborole and Beyond: The Emergence of Cyclic Hemiboronic Acids as a Versatile Chemotype in Medicine, Catalysis, and Materials

Cyclic hemiboronic acids are boron-containing heterocycles composed of one exocyclic boranol (B-OH) group, one endocyclic B-C bond, and one endocyclic B-heteroatom (O or N) bond. Compared to their open-form congeners, boronic acids, they are largely underexplored. Inspired by the recent success of the benzoxaborole ring system in drug discovery, highlighted by the approved products tavaborole and crisaborole, the last two decades have seen a continuous rise in interest toward other classes of nonaromatic and pseudoaromatic hemiboronic heterocycles. These boroheterocycles have been employed in various applications including organocatalysis, bioconjugation, drug discovery, as synthetic intermediates in natural product synthesis, and as components of new dynamic materials. This article brings together, using a structure-based organization, a comprehensive review of the current knowledge of these unique compounds. Preparative methods, structural characteristics, and important physical properties such as the open-closed equilibrium, acidity (p<i>K</i>_a), and molecular interactions are discussed and compared between different structural subtypes. Ring size and the nature of heteroatoms within the ring often exert dramatic differences in acidity, reactivity, and aromatic character of the heterocycle, which in turn enable their methodical application.