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Benzylic Fluorination Induced by a Charge-Transfer Complex with a Solvent-Dependent Selectivity Switch

Amiera Madani, Lucia Anghileri, Matthias Heydenreich, Heiko M. Möller and Bartholomäus Pieber*

*Department of Biomolecular Systems, Max-Planck-Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany, Email:

A. Madani, L. Anghileri, M. Heydenreich, H. M. Möller, B. Pieber, Org. Lett., 2022, 24, 5376-5380.

DOI: 10.1021/acs.orglett.2c02050

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A divergent strategy for the fluorination of phenylacetic acid derivatives is induced by a charge-transfer complex between Selectfluor and 4-(dimethylamino)pyridine. In the presence of water, decarboxylative fluorination through a single-electron oxidation is dominant. Non-aqueous conditions result in the clean formation of α-fluoro-α-arylcarboxylic acids.

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proposed mechanism

General experimental procedure for α-fluorination

An oven-dried vessel (19 x 100 mm) equipped with a stir bar was charged with substrate (1.8 mmol, 1 equiv, 0.2 mM), 4-dimethylaminopyridine (3.6 mmol, 2 equiv.) and Selectfluor (765.2 mg, 2.16 mmol, 1.2 equiv.). MeCN (9 mL) was added, the vessel was sealed and the mixture stirred at room temperature for one hour. HCl (10 mL, 1 M) was added and the mixture was extracted with diethylether (3 x 10 mL). The combined organic phases were dried over Na2SO4, filtered and concentrated. The product was purified by column chromatography (SiO2, Hexane/EtOAc or Hexane/MeOH) on a Grace™ Reveleris™ system.

Key Words

α-fluorination, Selectfluor

ID: J54-Y2022