Successive C–C bond cleavage, fluorination, trifluoromethylthio- and pentafluorophenylthiolation under metal-free conditions to provide compounds with dual fluoro-functionalization

The selective C–C bond cleavage and simultaneous formation of two C–F bonds and one C–S bond with DAST, CF3-DAST under metal-free/catalyst-free conditions is disclosed.

The resulting mixture was cooled to -20 °C, the diethylaminosulfurtrifluoride (0.15 mL, 1.0 mmol) was added slowly by syringe, stirred for 15 min at same temperature, then the trimethylsilyltrifluoromethane (0.16 mL, 1.0 mmol) was added slowly by syringe, and stirring for two hours under the same reaction temperature. After two hours, the solution was directly used for next step without purification. See below.
The solution was cooled to -10 °C and the 0.5M solution of CF 3 -DAST (0.2 mmol, 2.0 equiv, 0.45 mL taken from the solution above mentioned) or (0.4 mmol, 4.0 equiv, 0.9 mL taken from the solution above mentioned) in CH 2 Cl 2 was added slowly by syringe. Then the reaction mixture was stirred at -10 °C or room temperature for overnight, quenched by addition of water (10 mL), extracted with ethyl acetate (3 x 20 mL), dried over with Na 2 SO 4 and then concentrated in vacuo. The crude product was purified by flash column chromatography to provide the title compound 4a-4n and 4o.
Upon removal from the glove box, anhydrous THF (0.5 mL) was added via syringe under an atmosphere of argon and stirred at ambient temperature for 15 minutes.
The resulting mixture was cooled to -10 °C, the diethylaminosulfurtrifluoride (0.15 mL, 1.0 mmol) was added slowly by syringe, stirred for 15 min at same temperature, then the trimethyl(perfluorophenyl)silane (0.19 mL, 1.0 mmol) was added slowly by syringe, and stirring for two hours under the same reaction temperature, after two hours directly use for next step reactions without purifacation.

General procedure and product characterization data for 7b;
A flame-dried vessel was successively charged, under nitrogen, with β-keto esters 1b (19.0 mg, 0.1 mmol, 1.0 equiv) and anhydrous 1,4-dioxane (1.0 mL). The solution was cooled to -10 °C and the 0.5M solution of C 6 F 5 -DAST (0.2 mmol, 2.0 equiv, 0.46 mL) in CH 2 Cl 2 was added slowly by syringe. Then the reaction mixture was stirred at -10 °C or room temperature for overnight, quenched by addition of water (10 mL