Multifunctional Organoboron Compounds and Boralactonate Salts

Abstract

Organoboron compounds have gathered an important significance within the chemistry community on account of their wide range of applications in synthesis, catalysis, and medicinal chemistry. Even though the uses of boron compounds in drug discovery have been overlooked until the last several decades, boronic acid containing molecules have garnered increased attention due to the unique chemical properties of the boron center. Boron-functionalized 𝛼-aryl propionic acid non-steroidal anti-inflammatory drug derivatives (bora-NSAIDs) can be accessed via copper(I)-catalyzed alkene boracarboxylation, using CO2 and B2pin2. To explore and expand the current synthetic and future medicinal chemistry applications of these bora-NSAIDs, methods to derivatize the boron center need to be developed. Here, boron containing ibuprofen (bora-ibuprofen) synthesis via benchtop copper(I)-catalyzed alkene boracarboxylation was developed. Transesterification and transamination strategies have been employed to deprotect boron pinacol ester group in bora-ibuprofen, to synthesize additional bora-ibuprofen derivatives and subsequently isolate ibuprofen lactone boronic acid. Boracarboxylated products can be further functionalized by reacting them with potassium bifluoride under mild reaction conditions to afford air and moisture stable difluoroboralactonate salts. These Difluoroborolactonate salts exhibited remarkable stability under both acidic and basic hydrolytic conditions.