Mild and Chemoselective Carboxylic Acid Reduction Promoted by Borane Catalysis

Abstract

Although considerable advances have been made in developing chemoselective transformations of ubiquitous carboxylic acid groups, many challenges still exist. For instance, their selective reduction is problematic if both more nucleophilic and more electrophilic groups are present in the starting material. Here, we address this problem with a simple and mild protocol using bench-stable reagents at ambient temperatures. This platform is able to tolerate a diverse range of functionality, leaving ketones, esters, nitro-groups, olefins, nitriles and amides untouched. A combination of experimental and computational mechanistic experiments demonstrate that this reaction proceeds via hidden borane catalysis with small quantities of in situ generated BH₃ playing a key role in the exquisite selectivity that is observed.

Keywords: Boron; Density-Functional Calculations; Hydroboration; Reduction; Selectivity.