4-tert-butyl-1,1-difluorocyclohexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A reaction of 4-t-butylcyclohexanone (2 mmol) with diethylaminosulfur trifluoride (3.0 mmol) in CH2Cl2 (10 mL) containing TiCl4 (0.3 mmol) at room temperature gave a 99% conversion of starting material to products and a 67% yield of 1,1-difluoro-4-t-butylcyclohexane after 6 h. as determined by NMR (4-fluoroanisole as internal standard). gave a 99% conversion of starting material to products

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A reaction of 4-t-butylcyclohexanone (2 mmol) with diethylaminosulfur trifluoride (3.0 mmol) in CH2Cl2 (10 mL) containing Znl2 (0.3 mmol) at room temperature gave a 99% conversion of starting material to products and a 67% yield of 1,1-difluoro-4-t-butylcyclohexane after 6 h. as determined by NMR (4-fluoroanisole as internal standard). containing Znl2 (0.3 mmol) at room temperature gave a 99% conversion of starting material to products

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A reaction of 4-t-butylcyclohexanone (2 mmol) with diethylaminosulfur trifluoride (3.0 mmol) in CH2Cl2 (10 mL) containing BF3.OEt2 (0.3 mmol) at room temperature gave a 99% conversion of starting material to products and a 67% yield of 1,1-difluoro-4-t-butylcyclohexane after 6 h. as determined by NMR (4-fluoroanisole as internal standard). gave a 99% conversion of starting material to products

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A reaction of 4-t-butylcyclohexanone (2 mmol) with diethylaminosulfur trifluoride (3.0 mmol) in CH2Cl2 (10 mL) at room temperature gave a 99% conversion of starting material to products and a 67% yield of 1,1-difluoro-4-t-butylcyclohexane after 6 h. as determined by NMR (4-fluoroanisole as internal standard). gave a 99% conversion of starting material to products

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-t-butylcyclohexanone (308 mg, 2.0 mmol) in CH2Cl2 (10.0 mL) was added to N-ethyl-N-phenylaminosulfur trifluoride (627 mg, 3.0 mmol ) at room temperature under N2. BF3.OEt2 (100 mL) was added and the mixture was stirred for 6 h at room temperature. The mixture was washed with saturated NaHCO3, dried (Na2SO4), filtered and evaporated in vacuo. Proton and Fluorine NMR with 4-fluoroanisole (2 mmol) as internal standard showed that a 99% yield of 1,1-difluoro-4-t-butylcyclohexane was obtained. The mixture was washed with saturated NaHCO3 dried (Na2SO4) filtered evaporated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-t-butylcyclohexanone (308 mg, 2.0 mmol) in CH2Cl2 (10.0 mL) was added to diethylaminosulfur trifluoride (483 mg, 3.0 mmol ) at room temperature under N2. BF3.OEt2 (100 mL) was added and the mixture was stirred for 6 h at room temperature. The mixture was washed with saturated NaHCO3, dried (Na2SO4), filtered and evaporated in vacuo. Proton and Fluorine NMR with 4-fluoroanisole (2 mmol) as internal standard showed that a 67% yield of 1,1-difluoro-4-t-butylcyclohexane was obtained. The mixture was washed with saturated NaHCO3 dried (Na2SO4) filtered evaporated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Table 6 summarizes the results obtained on fluorination of 4-t-butyl cyclohexanone with the aminosulfur trifluorides. All of the compositions examined except N-naphthyl-N-phenylaminosulfur trifluoride converted the ketone to a mixture of 4-t-butyl-difluorocyclohexane and 4-t-butyl-1-fluorocyclohexene, with the former predominating. The fluorination of this ketone was much slower than observed for the fluorination of cyclooctanol. A complete conversion to the fluorinated products required several days at room temperature in CH2Cl2. However, addition of a catalytic amount of HF (generated in-situ from EtOH) accelerated the rate of reaction considerably. The reaction time was reduced from several days to ˜16 h when the diaryl, arylalkyl, and N-methoxyethyl-N-phenylaminosulfur trifluorides were reacted with 4-t-butylcyclohexanone in the presence of HF. The effect of HF on reaction rate was, however, less pronounced with the alkoxyalkyl aminosulfur trifluorides 37 and 41. A reasonable reaction time (40 h) for complete fluorination of the ketone with bis(methoxyethyl-aminosulfur trifluoride (41) was obtained when the reaction was carried out at 40° C. several days at room temperature the rate of reaction considerably The reaction time was reduced from several days to ˜16 h The effect of HF on reaction rate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-t-butylcyclohexanone (308 mg, 2.0 mmol) in CH2Cl2 (10.0 mL) was added to N-ethyl-N-phenylaminosulfur trifluoride (627 mg, 3.0 mmol ) at room temperature under N2. BF3.OEt2 (100 mL) was added and the mixture was stirred for 6 h at room temperature. The mixture was washed with saturated NaHCO3, dried (Na2SO4), filtered and evaporated in vacuo. Proton and Fluorine NMR with 4-fluoroanisole (2 mmol) as internal standard showed that a 99% yield of 1,1-difluoro-4-t-butylcyclohexane was obtained. The mixture was washed with saturated NaHCO3 dried (Na2SO4) filtered evaporated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-t-butylcyclohexanone (308 mg, 2.0 mmol) in CH2Cl2 (10.0 mL) was added to diethylaminosulfur trifluoride (483 mg, 3.0 mmol ) at room temperature under N2. BF3.OEt2 (100 mL) was added and the mixture was stirred for 6 h at room temperature. The mixture was washed with saturated NaHCO3, dried (Na2SO4), filtered and evaporated in vacuo. Proton and Fluorine NMR with 4-fluoroanisole (2 mmol) as internal standard showed that a 67% yield of 1,1-difluoro-4-t-butylcyclohexane was obtained. The mixture was washed with saturated NaHCO3 dried (Na2SO4) filtered evaporated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of diethylaminosulfinium tetrafluoroborate (344 mg, 1.5 mmol), triethylamine trihydrofluoride (326 μl, 2.0 mmol) and triethylamine (139 μl, 1.0 mmol) in dichloromethane (3.0 mL) at room temperature is added 4-tert-butylcyclohexanone (154 mg, 1.0 mmol). The reaction mixture is stirred for 22 hours, then an aqueous solution of sodium bicarbonate (5%) is added and stirring is continued for 15 minutes. The phases are separated and the aqueous layer is extracted twice using dichloromethane. The organic phases are combined and dried with magnesium sulphate. The solution is passed through a pad of silica gel with dichloromethane elution. Solvent are evaporated in vacuo to provide 4-t-butyl-1,1-difluorocyclohexane (160 mg, 91%) as a clear liquid, admixed with 0.8% of the corresponding vinyl fluoride. stirring is continued for 15 minutes The phases are separated the aqueous layer is extracted twice using dichloromethane dried with magnesium sulphate The solution is passed through a pad of silica gel with dichloromethane elution Solvent are evaporated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of diethylaminosulfinium tetrafluoroborate (593 mg, 2.6 mmol) in dichloromethane (10 mL) at room temperature is added 4-tert-butylcyclohexanone (200 mg, 1.3 mmol) and triethylamine trihydrofluoride (266 μl, 1.3 mmol). The reaction mixture is stirred for 4 hours, then an aqueous solution of sodium bicarbonate (5%) is added and stirring is continued for 30 minutes. The organic phase is isolated and dried with magnesium sulphate. The solution is diluted with pentane (10 mL) and the solution is passed through a pad of silica gel with pentane elution. Solvent are evaporated in vacuo to provide 4-t-butyl-1,1-difluorocyclohexane (120 mg, 53%) as a clear liquid, admixed with 3% of the corresponding vinyl fluoride. Major compound: 1H NMR (CDCl3) 2.09-1.95 (m, 2H), 1.76-1.67 (m, 2H), 1.65-1.51 (m, 2H), 1.30-1.15 (m, 2H), 1.02-0.97 (s, 1H), 0.80 (s, 9H); 19F NMR (CDCl3)-91.9 (d, J=232.6 Hz, 1F), −103.5 (dm, J=232.6 Hz, 1F). stirring is continued for 30 minutes The organic phase is isolated dried with magnesium sulphate The solution is diluted with pentane (10 mL) the solution is passed through a pad of silica gel with pentane elution Solvent are evaporated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A reaction of 4-t-butylcyclohexanone (2 mmol) with diethylaminosulfur trifluoride (3.0 mmol) in CH2Cl2 (10 mL) containing TiCl4 (0.3 mmol) at room temperature gave a 99% conversion of starting material to products and a 67% yield of 1,1-difluoro-4-t-butylcyclohexane after 6 h. as determined by NMR (4-fluoroanisole as internal standard). gave a 99% conversion of starting material to products