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

Tharwat Mohy El Dine (1) , William Erb (1) , Yohann Berhault (1) , Jacques Rouden (1) , Jérôme Blanchet (1)

1 LCMT - Laboratoire de chimie moléculaire et thioorganique

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.

Domains: Chemical Sciences; Organic chemistry

Tharwat Mohy El Dine, William Erb, Yohann Berhault, Jacques Rouden, Jérôme Blanchet. Catalytic Chemical Amide Synthesis at Room Temperature: One More Step Toward Peptide Synthesis. Journal of Organic Chemistry, 2015, 80 (9), pp.4532 - 4544. ⟨10.1021/acs.joc.5b00378⟩. ⟨hal-01793141⟩