Anhydrous Tetramethylammonium Fluoride for Room-Temperature SNAr Fluorination

Sydonie D. Schimler, Sarah J. Ryan, Douglas C. Bland, John E. Anderson, Melanie S. Sanford

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

This paper describes the room-temperature SNAr fluorination of aryl halides and nitroarenes using anhydrous tetramethylammonium fluoride (NMe4F). This reagent effectively converts aryl-X (X = Cl, Br, I, NO2, OTf) to aryl-F under mild conditions (often room temperature). Substrates for this reaction include electron-deficient heteroaromatics (22 examples) and arenes (5 examples). The relative rates of the reactions vary with X as well as with the structure of the substrate. However, in general, substrates bearing X = NO2 or Br react fastest. In all cases examined, the yields of these reactions are comparable to or better than those obtained with CsF at elevated temperatures (i.e., more traditional halex fluorination conditions). The reactions also afford comparable yields on scales ranging from 100 mg to 10 g. A cost analysis is presented, which shows that fluorination with NMe4F is generally more cost-effective than fluorination with CsF.

Original languageEnglish (US)
Pages (from-to)12137-12145
Number of pages9
JournalJournal of Organic Chemistry
Volume80
Issue number24
DOIs
StatePublished - Dec 9 2015

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