Clickable coupling of carboxylic acids and amines at room temperature mediated by SO2F2: a significant breakthrough for the construction of amides and peptide linkages?

Organic & Biomolecular Chemistry Pub Date: 2019-03-28 DOI: 10.1039/C9OB00699K

Abstract

The construction of amide bonds and peptide linkages is one of the most fundamental transformations in all life processes and organic synthesis. The synthesis of structurally ubiquitous amide motifs is essential in the assembly of numerous important molecules such as peptides, proteins, alkaloids, pharmaceutical agents, polymers, ligands and agrochemicals. A method of SO2F2-mediated direct clickable coupling of carboxylic acids with amines was developed for the synthesis of a broad scope of amides in a simple, mild, highly efficient, robust and practical manner (>110 examples, >90% yields in most cases). The direct click reactions of acids and amines on a gram scale are also demonstrated using an extremely easy work-up and purification process of washing with 1 M aqueous HCl to provide the desired amides in greater than 99% purity and excellent yields.

Graphical abstract: Clickable coupling of carboxylic acids and amines at room temperature mediated by SO2F2: a significant breakthrough for the construction of amides and peptide linkages
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