Mild and Chemoselective Carboxylic Acid Reduction Promoted by Borane Catalysis

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, ole-fins, 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.

Automated summary

Although challenges still exist, we have developed a simple and mild protocol that selectively reduces starting materials containing both more nucleophilic and more electrophilic groups at room temperature. This protocol is able to preserve the integrity of other functional groups.