Direct Boronic Acid Promoted Amidation of Carboxylic Acids with Poorly Nucleophilic Amines

Abstract Direct amidation of carboxylic acids with poorly nucleophilic amines such as anilines is a notorious challenge in organic chemistry. Previously reported methodologies for direct amidation tend to report none or just a few examples with simple anilines, which generally react at temperatures over 100 °C. To address this challenge and develop a mild and direct dehydrative anilide synthesis, herein a series of novel boronic acids with a biphenyl scaffold were prepared based on a design concept of bifunctional activation. The optimal thioether‐substituted biphenylboronic acid, 1e , exhibits good reactivity in promoting the amidation reaction of various anilines at 85 °C in fluorobenzene, including halogenated anilines, electron‐rich and electron‐deficient anilines, and the heterocyclic 6‐aminoquinoline. Variations of the aliphatic carboxylic acid are possible, affording the corresponding anilides in good yields. The efficiency and recyclability of boronic acid 1e were demonstrated on a gram‐scale amidation reaction.