TiF4-catalyzed direct amidation of carboxylic acids and amino acids with amines

Org Biomol Chem. 2024 Feb 28;22(9):1915-1919. doi: 10.1039/d3ob01943h.

Abstract

Unlike other metal fluorides, catalytic titanium tetrafluoride enhances the direct amidation of aromatic and aliphatic carboxylic acids and N-protected amino acids in refluxing toluene. While aromatic acids were converted to amides with 10 mol% of the catalyst within 24 h, aliphatic acids underwent a faster reaction (12 h), with lower catalyst loading (5 mol%). This protocol is equally efficient with alkyl and aryl amines providing a variety of carboxamides and peptides in 60-99% yields.