Fluorination of 4-alkyl-substituted phenols and aromatic ethers with fluoroxy and N-F reagents: Cesium fluoroxysulfate and N-fluoro-1,4-diazonia-bicyclo[2.2.2]octane dication salts case

•Fluorination of 4-alkyl-substituted phenols or aromatic ethers with cesium fluoroxysulfate, Selectfluor F-TEDA-BF4 or Accufluor NFTh gave three types of products.•Bulkiness of alkyl group on aromatic ring and at phenolic oxygen regulates the relative distribution of products.•Reactions performed with NFTh are more selective than those with F-TEDA-BF4 and in MeOH more selective than in MeCN.

4-Alkyl-substituted phenols and aromatic ethers were comparatively fluorinated with electrophilic fluorinating reagents such as cesium fluoroxysulfate (CFS), Selectfluor™ F-TEDA-BF4, and Accufluor™ NFTh in MeCN or MeOH. Reactions resulted in the formation of three types of products: 2-fluoro-4-alkyl-substituted corresponding compounds (5) as a result of ortho fluorination process, 4-alkyl-4-fluoro-cyclohexa-2,5-dienone compounds (6), resulting after an addition–elimination process, and 4-fluorosubstituted corresponding compounds (7) derived from ipso attack and release of the 4-alkyl group. The distribution of products depends on the bulkiness of alkyl groups at both positions and reaction media. The reaction in methanol proved more selective toward the formation of 2-fluoro derivatives. Tyramin and l-tyrozine were transformed with NFTh reagent in methanol to their fluorophenyl-substituted derivatives in good yield.

Graphical abstractFluorination of 4-alkyl-substituted phenols or corresponding alkyl ethers with cesium fluoroxysulfate, Selectfluor F-TEDA-BF4 or Accufluor NFTh resulted in the formation of three types of products: 2-fluoro-substituted derivatives, 4-fluoro-dealkylated products, and 4-alkyl-4-fluoro-cyclohexa-2,5-dienone derivatives.Figure optionsDownload full-size imageDownload as PowerPoint slide