Catalytic Chemical Amide Synthesis at Room Temperature: One More Step Toward Peptide Synthesis

Abstract

An efficient method has been developed for direct amide bond synthesis between carboxylic acids and amines via (2-(thiophen-2-ylmethyl)phenyl)boronic acid as a highly active bench-stable catalyst. This catalyst was found to be very effective at room temperature for a large range of substrates with slightly higher temperatures required for challenging ones. This methodology can be applied to aliphatic, α-hydroxyl, aromatic, and heteroaromatic acids as well as primary, secondary, heterocyclic, and even functionalized amines. Notably, N-Boc-protected amino acids were successfully coupled in good yields with very little racemization. An example of catalytic dipeptide synthesis is reported.

Borinic acid catalysed peptide synthesis

“…8 This result was previously improved using our catalyst 5 (ee: 94%). 7 Interestingly, 9h afforded the desired amide 11 in 96% yield with the complete retention of enantiopurity (ee > 99%, Scheme 1). First attempts of coupling two protected α-amino acids at room temperature resulted in the total absence of conversion.…”

Avanços recentes na hidroaminação de compostos insaturados

“…Para a síntese dessa classe de compostos, diversas metodologias para formação de ligação C-N foram desenvolvidas, dentre essas destacam-se N-alquilação, 1,2 aminação redutiva com compostos carbonílicos, 3,4 N-acilação 5,6 e acoplamento cruzado C-N. 7,8 Entre os métodos modernos para construção de compostos nitrogenados complexos, a hidroaminação de compostos insaturados vem ganhando destaque e desperta interesse da comunidade científica. 9,10 Essa abordagem impacta na economia de átomos do processo, o que é benéfico do ponto de vista da química verde.…”

Chiral Integrated Catalysts Composed of Bifunctional Thiourea and Arylboronic Acid: Asymmetric Aza-Michael Addition of α,β-Unsaturated Carboxylic Acids

“…From the perspective of atom and step economy, achieving a direct Michael reaction of α,β-unsaturated carboxylic acids without the use of any activating templates is highly desirable. Despite strong synthetic utility, the direct Michael addition of α,β-unsaturated carboxylic acids has never been reported, except for an enzyme-catalyzed azaMichael addition 13,14) ; very few strategies have been exploited to catalytically activate the hydroxy group of carboxylic acids via transient covalent bond formation.By contrast, since the discovery by Yamamoto and Ishihara that electron-deficient arylboronic acids are efficient activators of carboxylic acids in direct amidation reactions, [15][16][17][18] 24,25) Hall reported that different types of arylboronic acids could be used for the cycloaddition of α,β-unsaturated carboxylic acids to dienes and 1,3-dipoles. 20,21) Recently, we also revealed that aminoarylboronic acid was the best catalyst for the intramolecular hetero-Michael addition of α,β-unsaturated carboxylic acids bearing sulfonamides or phenols.…”

“…By contrast, since the discovery by Yamamoto and Ishihara that electron-deficient arylboronic acids are efficient activators of carboxylic acids in direct amidation reactions, [15][16][17][18] 24,25) Hall reported that different types of arylboronic acids could be used for the cycloaddition of α,β-unsaturated carboxylic acids to dienes and 1,3-dipoles. 20,21) Recently, we also revealed that aminoarylboronic acid was the best catalyst for the intramolecular hetero-Michael addition of α,β-unsaturated carboxylic acids bearing sulfonamides or phenols.…”

“…By contrast, since the discovery by Yamamoto and Ishihara that electron-deficient arylboronic acids are efficient activators of carboxylic acids in direct amidation reactions, [15][16][17][18] a series of arylboronic acids have been developed for the activation of various functional groups, including α,β-unsaturated carboxylic acids, [19][20][21] alcohols, 22) carbonyl compounds, 23) and others. 24,25) Hall reported that different types of arylboronic acids could be used for the cycloaddition of α,β-unsaturated carboxylic acids to dienes and 1,3-dipoles.…”