Development of Diboronic Acid Anhydride-Catalyzed Dehydrative Amidations

Amide bonds are important chemical linkages constituting many natural products and pharmaceuticals. Although the dehydrative condensation of the carboxylic acids with amines is the most straightforward approach to construct amide bonds, the common methods require a stoichiometric amount of coupling reagents, which causes the problems associated with poor atom economy and practical operation. In contrast, the catalytic direct dehydrative amidation is an ideal approaches because water is the only byproduct. After the pioneering report by Yamamoto and Ishihara in 1996, the variety of organoboron-catalyzed dehydrative amidations have been developed for a quarter of a century. This article highlights our recent studies on diboronic acid anhydride (DBAA)-catalyzed dehydrative amidations. DBAA designed on the basis of a recent mechanism has been identified as a powerful catalyst for dehydrative amidations of beta- or alpha-hydroxy carboxylic acids. Under optimized conditions, the dehydrative condensation could be promoted with only 0.01 mol% of catalyst. Another noteworthy feature is that the catalysis did not require any dehydrative operations such as azeotropic reflux with a Dean-Stark apparatus or adding molecular sieves, showing excellent chemoselectivities for beta-hydroxy carboxylic acids over simple carboxylic acids. DBAA was also applicable to the catalytic synthesis of beta- or alpha-hydroxy carboxylic acid-derived Weinreb amides and catalytic peptide bond formations of beta-hydroxy-alpha-amino acids. The synthetic utility of the catalysis was demonstrated by the concise synthesis of pharmaceutical, chiral building block, and acyloin natural products.