Deoxyfluorination of Carboxylic Acids via an In Situ Generated Trifluoromethoxide Salt

Org Lett. 2023 Dec 22;25(50):9025-9029. doi: 10.1021/acs.orglett.3c03706. Epub 2023 Dec 8.

Abstract

An in situ generated pyridinium trifluoromethoxide salt (PyOCF3) is a highly effective deoxyfluorination reagent for the synthesis of acid fluorides. PyOCF3 is formed at room temperature from the reaction of 2,4-dinitro(trifluoromethoxy)benzene with 4-dimethylaminopyridine. PyOCF3 undergoes slow release of fluorophosgene and fluoride, which serve as the electrophile and nucleophile, respectively, for deoxyfluorination. A wide substrate scope and high functional group tolerance are demonstrated. Furthermore, the acid fluorides can be purified by filtration and telescoped to various known reactions.