Synthesis and synthetic applications of ( 4-hydroxyphenyl ) perfluoroalkyl-methanols

Development of the convenient method for the synthesis of (hydroxyphenyl)perfluoroalkylmethanols was achieved by the Meerwein-Ponndorf-Verley (MPV) type reduction of the in situ-generated perfluoroalkylated ketones as the key step, and the benzylic OH group of the resultant alcohols was converted to H or Rf(CH2)nO by way of the corresponding chlorides whose transformation was not easy by any other methods.


General information
Most of reactions where an organic solvent was employed were performed under argon with magnetic stirring using flame-dried glassware. Unless otherwise noted, materials were obtained from commercial suppliers including anhydrous THF, Et2O, and CH2Cl2, and were used without further purification. Analytical thin-layer chromatography (TLC) was routinely used for monitoring reactions by generally using a mixture of hexane and ethyl acetate. Spherical neutral silica gel (63-210 nm) was employed for usual column chromatography.
1 H (300.40 MHz), 13 C (75.45 Hz), and 19 F (282.65 Hz) NMR spectra were recorded in CDCl3 unless otherwise noted, and chemical shifts were reported in parts per million (ppm), downfield from internal tetramethylsilane (Me4Si: d 0.00, for 1 H and 13 C) or hexafluorobenzene (C6F6: d -163.00 for 19 F). Data were tabulated in the following order: number of protons, multiplicity (s, singlet; d, doublet; t, triplet; q, quartet; quint, quintet; sex, sextet; m, multiplet; br, broad peak), coupling constants in Hertz. In the case of 13 C NMR for the compounds with C3F7 and C6F13 groups, because multiple coupling of fluorine-possessing carbon atoms made their observation difficult even after long data acquisition time, these data are not shown. Infrared (IR) spectra were reported in wave numbers (cm -1 ). High resolution mass spectrometry was performed by the positive ionization mode.

General procedure for the deprotection of the THP group (General procedure 4)
To a 50 mL round-bottomed flask were added 4fb (1.8814 g, 5.0000 mmol), MeOH (15 mL) and p-TsOH•H2O (0.0978 g, 0.514 mmol, 10 mol%) and the mixture was stirred at r.t. for 1 h. Then, sat. NaHCO3 aq. was added to the mixture and MeOH was removed in vacuo.
The residue was extracted with Et2O three times and the Et2O layer was dried over anhydrous  [8] Following to the "General procedure 3" using 4aa (0.1447 g, 0.3077 mmol), 0.0415 g (0.216 mmol) of 2aa was obtained in 72% yield as a white solid.

4-(1-Chloro-2,2,3,3,4,4,4-heptafluorobutyl)phenol (7b)
To a 30 mL two-necked round-bottomed flask equipped with reflux condenser were added 2ab (0.5843 g, 2.000 mmol) and THF (6 mL), where a solution containing SOCl2 (0.20 mL, 2.4 mmol) and pyridine (0.18 ml, 2.2 mmol) in THF (2.0 mL) was introduced slowly at -10 °C, and the mixture was stirred for 1 h at the same temperature. Then, DMF (0.0143 g, 0.196 mmol) in THF (1 mL) was added and the reaction mixture was stirred at 80 °C for 1 h. The reaction mixture was quenched with H2O and the mixture was extracted with Et2O three times, and the usual workup afforded a crude product 7b which was used in the next reaction without further purification. Because this chlorinated product was gradually decomposed, it must be used for the next reaction as soon as possible.  Chloro-2,2,3,3,4,4