Catalytic amide formation from non-activated carboxylic acids and amines

Abstract

The amide functionality is found in a wide variety of biological and synthetic structures such as proteins, polymers, pesticides and pharmaceuticals. Due to the fact that synthetic amides are still mainly produced by the aid of coupling reagents with poor atom-economy, the direct catalytic formation of amides from carboxylic acids and amines has become a field of emerging importance. A general, efficient and selective catalytic method for this transformation would meet well with the increasing criterias for green 10 chemistry. This review covers catalytic and synthetically relevant methods for direct condensation of carboxylic acids and amines. A comprehensive overview of homogeneous and heterogeneous catalytic methods is presented, covering biocatalysis, Lewis acid catalysts based on boron and metals as well an assortment of other types of catalysts.

Borinic acid catalysed peptide synthesis

“…Despite those great accomplishments, a catalyst that would be able to achieve similar efficiency is still to be discovered. Albeit the catalytic synthesis of amides from simple carboxylic acids and amines has been reviewed several times 3 , almost no information concerning the assembly of two α-amino acids derivatives is available. Compared to simple carboxylic acids and amines, protected α-amino acids are challenging substrates, due to their weaker nucleophilic character of the amine function and increased steric hindrance caused by the side chain.…”

Synthesis and Crystallographic Characterization of a Maleimide Derivative of Tryptamine

“…Indeed, thermal and uncatalyzed amide formation has been scarcely reported [10,11] especially when the nucleophile is conjugated amide.…”

Organocatalysis: Fundamentals and Comparisons to Metal and Enzyme Catalysis

“…Nature makes amides with enzymes as catalysts. In the laboratory mostly lipases (e.g., peptide amidase extracted from orange peel, Candida antartica lipase B, Candida cylindracea lipase, Novozym, porcine pancreas lipase) and microorganism (e.g., Bacillus cereus, Streptomyces halstedii, and Bacillus subtilis) have been used as biocatalysts for direct amidification of carboxylic acids [157]. Since the biocatalysts cannot accept any amines and carboxylic acids as reagents, chemical catalysts are highly desired.…”

“…The amine may also react with HATU and lead to 40 + 41 (Scheme 21). In terms of atomic economy [154,155], these reactions are poorly behaved and thus efficient catalysts permitting the direct amide formation (Scheme 20) under smooth conditions are most welcome [156,157]. Nature makes amides with enzymes as catalysts.…”