* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference:
[1] Chemical Communications, 2007, # 48, p. 5149 - 5151
2
[ 80351-58-2 ]
[ 1535-65-5 ]
Yield
Reaction Conditions
Operation in experiment
71%
With n-butyllithium; chloro-trimethyl-silane In tetrahydrofuran at -78℃; for 6 h;
To a solution of bromodifluoromethyl phenyl sulfone 9 (0.54 g, 2.00 mmol) and TMSCl (0.38 mL, 3.00 mmol) in dry THF cooled to -78 °C was added dropwise n-BuLi (1.6 M, 2.25 mL, 3.60 mmol). Reaction was stirred for 6 h at -78 °C. Saturated aqueous NH4Cl 15mL) was then added at -78 °C, the residue was brought to room temperature and extracted with Et2O (3 15 mL). The combined organic layers were washed with brine, water, then dried (Na2SO4) and concentrated under reduced pressure.The crude product was purified by silica gel column chromatography using CH2Cl2 and hexane as eluents (3:2). Rf = 0.38 (CH2Cl2/hexane,3:2).Yield: 0.27 g, 1.4 mmol, 71percent.
Reference:
[1] European Journal of Organic Chemistry, 2012, # 30, p. 5943 - 5952,10
[2] European Journal of Organic Chemistry, 2012, # 30, p. 5943 - 5952
[3] Journal of Fluorine Chemistry, 2015, vol. 179, p. 175 - 178
[4] Tetrahedron Letters, 2005, vol. 46, # 48, p. 8273 - 8277
3
[ 1073-67-2 ]
[ 80351-58-2 ]
[ 1535-65-5 ]
[ 1421521-00-7 ]
Reference:
[1] European Journal of Organic Chemistry, 2012, # 30, p. 5943 - 5952,10
[2] European Journal of Organic Chemistry, 2012, # 30, p. 5943 - 5952
2,2-difluoro-1-(3-iodophenyl)-2-(phenylsulfonyl)ethan-1-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
General procedure: In the glove box, zinc powder (206.0 mg, 3.15 mmol) was added into a Schlenk tube. Anhydrous DMF (10.5 mL) was added and the mixture was stirred at room temperature. Chlorotrimethylsilane (66.5 muL, 0.52 mmol) was then added into the mixture to activate zinc powder. Five minutes later, PhSO2CF2Br (2) (2.1 mmol) was added into the suspension. The reaction proceeded smoothly in 15 min to give (phenylsulfonyl)difluoromethylzinc reagent (?XZnCF2SO2Ph?, 3). The mixture was kept at room temperature to precipitate the remaining zinc powder, and the solution was directly used for next step. In the glove box, 2-naphthaldehyde (156.2 mg, 1.0 mmol) was added into another Schlenk tube. Anhydrous DMF (5 mL) was added and the mixture was stirred at room temperature. The DMF solution of ?XZnCF2SO2Ph? (3) (10 mL, corresponding to the reaction of ca. 2.0 mmol of PhSO2CF2Br and ca. 3.0 mmol of zinc powder) was added to the solution of 2-naphthaldehyde dropwise. The mixture was stirred at room temperature for 5 h, and aqueous HCl (2 M, 10 mL) was added to quench the reaction. After extraction with ethyl acetate for three times, the organic phase was washed with brine, and then dried over anhydrous Na2SO4. After the solution was filtered and evaporated under vacuum, the residue was subjected to silica gel column chromatography (eluting with petroleum ether/ethyl acetate) to give the corresponding difluoromethylated carbinol 4a as a white solid (307.5 mg, 88%).
2,2-difluoro-1-mesityl-2-(phenylsulfonyl)ethan-1-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
93%
Stage #1: [(bromodifluoromethyl)sulfonyl]benzene With chloro-trimethyl-silane; zinc In N,N-dimethyl-formamide at 20℃; for 0.25h; Glovebox; Schlenk technique;
Stage #2: mesytaldehyde With lithium chloride In N,N-dimethyl-formamide at 20℃; for 5h; Glovebox; Schlenk technique;
4.3.1 Typical procedures for nucleophilic difluoromethylation of aldehydes with (phenylsulfonyl)difluoromethylzinc reagent (Method A)
General procedure: In the glove box, zinc powder (206.0 mg, 3.15 mmol) was added into a Schlenk tube. Anhydrous DMF (10.5 mL) was added and the mixture was stirred at room temperature. Chlorotrimethylsilane (66.5 μL, 0.52 mmol) was then added into the mixture to activate zinc powder. Five minutes later, PhSO2CF2Br (2) (2.1 mmol) was added into the suspension. The reaction proceeded smoothly in 15 min to give (phenylsulfonyl)difluoromethylzinc reagent (“XZnCF2SO2Ph”, 3). The mixture was kept at room temperature to precipitate the remaining zinc powder, and the solution was directly used for next step. In the glove box, 2-naphthaldehyde (156.2 mg, 1.0 mmol) was added into another Schlenk tube. Anhydrous DMF (5 mL) was added and the mixture was stirred at room temperature. The DMF solution of “XZnCF2SO2Ph” (3) (10 mL, corresponding to the reaction of ca. 2.0 mmol of PhSO2CF2Br and ca. 3.0 mmol of zinc powder) was added to the solution of 2-naphthaldehyde dropwise. The mixture was stirred at room temperature for 5 h, and aqueous HCl (2 M, 10 mL) was added to quench the reaction. After extraction with ethyl acetate for three times, the organic phase was washed with brine, and then dried over anhydrous Na2SO4. After the solution was filtered and evaporated under vacuum, the residue was subjected to silica gel column chromatography (eluting with petroleum ether/ethyl acetate) to give the corresponding difluoromethylated carbinol 4a as a white solid (307.5 mg, 88%).