康 · 学术 | Reaction of the Day No. 1764

Catalytic Amidation of Carboxylic Acids Using ortho-Aminophenylboronic Acids

Veera K. Bruce-Salmenkivi, Mikko Passiniemi, and Petri M. Pihko*

Department of Chemistry and NanoScience Center, University of Jyv?skyl?, Jyv?skyl? FI-40014, Finland;

—ACS Org. Inorg. Au, 2026, 6, 422–429.

Recommended by Qifei Hu _ SC

KEY WORDS: C(=O)-N (成键类型),Carboxylic acids, Amines (原料), Amide (产物), Amidation (反应类型), ortho-Aminophenylboronic Acids,2-PPBA (其他)

ABSTRACT: Ortho-Substituted boronic acids have demonstrated significant potential as catalysts for direct amidation reactions, providing a sustainable alternative to conventional coupling reagents. We report the screening of ortho-functionalized arylboronic acids, including four literature benchmarks, as catalysts for the direct condensation of amines and carboxylic acids. The commercially available ortho-aminophenylboronic acids, specifically (2-(piperidin-1-yl)phenyl)boronic acid (2-PPBA), emerge as the optimal catalyst, providing amides from a range of carboxylic acids and amines.

Substrate Scope

Amidation of Protected Amino Acids

Summary and Comments

Recently, Prof. Petri M. Pihko and his group presented a structurally simple and readily accessible catalyst, 2-PPBA, for the direct amidation of carboxylic acids with amines. The catalytic protocol obviates the use of halogenated solvents and additional drying agents, enabling amidation reactions in a more atom-economical, sustainable, and operationally straightforward manner. Racemization of the product was generally not significant under the reaction conditions with α-chiral carboxylic acids; however, in the synthesis of dipeptides, the amine donor components were often partially epimerized. Nevertheless, given the simplicity of the catalyst (only a single boronic acid functionality) and the high activity of the catalyst in benchmark experiments, this study offers an attractive alternative to classical amide coupling methods for a wide variety of substrates.