4-iodobut-1-ene

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 500 mL round-bottomed flask (t=g) was added crude 4-iodobut-1-ene (11.51 g, 63.2 mmol) in Et2O (100 mL) to give a colorless solution. After cooling to −78° C. under nitrogen, tBuLi (80 mL, 136 mmol) was added dropwise via syringe. The mixture was slowly warmed up to room temperature while stirring for 2 hours. After 20 minutes at room temperature, the mixture was cooled to −78° C. and ethyl 2,3-difluorobenzoate (4.28 mL, 28.7 mmol) was added dropwise via syringe. The mixture was gradually warmed up to room temperature over 30 minutes. The reaction was quenched by water and the volatiles were evaporated. The residue was partitioned between water and EtOAc. The layers were separated and the organic layer was washed with brine, dried with Na2SO4 and concentrated to a light yellow oil. Purification up to 40% Et2O in hexane afforded the desired product as a colorless oil: (1.41 g, 19%). 1H NMR (400 MHz, CDCl3) δ 7.31-7.22 (m, 1H), 7.10-7.03 (m, 2H), 5.82-5.70 (m, 2H), 4.97-4.85 (m, 4H), 2.20-2.00 (m, 4H), 2.00-1.75 (m, 4H). to give a colorless solution The mixture was slowly warmed up to room temperature After 20 minutes at room temperature the mixture was cooled to −78° C. The mixture was gradually warmed up to room temperature over 30 minutes The reaction was quenched by water the volatiles were evaporated The residue was partitioned between water and EtOAc The layers were separated the organic layer was washed with brine dried with Na2SO4 concentrated to a light yellow oil Purification up to 40% Et2O in hexane

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 6-bromo-1-indanone (0.5330 g, 2.52 mmol) in dry THF (10 mL) was added NaH (0.3380 g, 60% in a mineral oil, 8.45 mmol) at 0° C. under nitrogen. After being stirred for 10 min, 4-iodobut-1-ene (1.3450 g, 7.39 mmol) was added and then the mixture was stirred at ambient temperature for 20 h. The reaction mixture was cooled to 0° C., quenched with 1 N HCl, extracted with ethyl acetate, and dried over Na2SO4. After the solvents were evaporated, the residue was purified by chromatography on silica gel eluted with hexanes/ethyl acetate to afford 0.1304 g of 6-bromo-2,2-di(but-3-en-1-yl)-2,3-dihydro-1H-inden-1-one. LC-MS tR=2.33 min in 3 min chromatography, m/z 319, 321 (MH+); 1H NMR (400 MHz, CDCl3) δ 7.84 (s, 1H), 7.67 (d, J=8 Hz, 1H), 7.33 (d, J=8 Hz, 1H), 5.76-5.66 (m, 2H), 4.94-4.87 (m, 4H), 2.98 (s, 2H), 1.98-1.63 (m, 8H); 13C NMR (100 MHz, CDCl3) δ 209.23, 151.43, 138.85, 137.85, 137.54, 127.94, 126.75, 121.55, 114.81, 52.87, 37.28, 36.58, 28.54. the mixture was stirred at ambient temperature for 20 h quenched with 1 N HCl extracted with ethyl acetate dried over Na2SO4 After the solvents were evaporated the residue was purified by chromatography on silica gel eluted with hexanes/ethyl acetate

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

Procedure: Into a 2 liter glass autoclave heated at the desidered temperature, toluene, 1-iodo-3-butene, V(acetylacetonate)3 and AlEt2I were introduced under nitrogen flow. A continuous constant ratio ethylene/propylene flow was then introduced. were introduced under nitrogen flow

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

Procedure: 0.41 g of {[5-(1-methyl-1-hydroxyethyl)isoxazol-3-yl]methyl}malononitrile and 0.63 g of 4-iodo-1-butene were dissolved in 6 ml of N,N-dimethylformamide, and 0.55 g of potassium carbonate was then added under ice-cooling. The mixture was stirred at room temperature overnight. After water was added, the reaction mixture was extracted with methyl-t-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 0.43 g of (3-butenyl){[5-(1-methyl-1-hydroxyethyl)isoxazol-3-yl]methyl}malononitrile represented by the following formula: cooling the reaction mixture was extracted with methyl-t-butyl ether The organic layer was washed with water dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure

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

Procedure: 0.41 g of {[5-(1-methyl-1-hydroxyethyl)isoxazol-3-yl]methyl}malononitrile and 0.63 g of 4-iodo-1-butene were dissolved in 6 ml of N,N-dimethylformamide, and 0.55 g of potassium carbonate was then added under ice-cooling. The mixture was stirred at room temperature overnight. After water was added, the reaction mixture was extracted with methyl-t-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 0.43 g of (3-butenyl){[5-(1-methyl-1-hydroxyethyl)isoxazol-3-yl]methyl}malononitrile represented by the following formula: cooling the reaction mixture was extracted with methyl-t-butyl ether The organic layer was washed with water dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure

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

Procedure: 0.41 g of {[5-(1-methyl-1-hydroxyethyl)isoxazol-3-yl]methyl}malononitrile and 0.63 g of 4-iodo-1-butene were dissolved in 6 ml of N,N-dimethylformamide, and 0.55 g of potassium carbonate was then added under ice-cooling. The mixture was stirred at room temperature overnight. After water was added, the reaction mixture was extracted with methyl-t-butyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 0.43 g of (3-butenyl){[5-(1-methyl-1-hydroxyethyl)isoxazol-3-yl]methyl}malononitrile represented by the following formula: cooling the reaction mixture was extracted with methyl-t-butyl ether The organic layer was washed with water dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 500 mL round-bottomed flask (t=g) was added crude 4-iodobut-1-ene (11.51 g, 63.2 mmol) in Et2O (100 mL) to give a colorless solution. After cooling to −78° C. under nitrogen, tBuLi (80 mL, 136 mmol) was added dropwise via syringe. The mixture was slowly warmed up to room temperature while stirring for 2 hours. After 20 minutes at room temperature, the mixture was cooled to −78° C. and ethyl 2,3-difluorobenzoate (4.28 mL, 28.7 mmol) was added dropwise via syringe. The mixture was gradually warmed up to room temperature over 30 minutes. The reaction was quenched by water and the volatiles were evaporated. The residue was partitioned between water and EtOAc. The layers were separated and the organic layer was washed with brine, dried with Na2SO4 and concentrated to a light yellow oil. Purification up to 40% Et2O in hexane afforded the desired product as a colorless oil: (1.41 g, 19%). 1H NMR (400 MHz, CDCl3) δ 7.31-7.22 (m, 1H), 7.10-7.03 (m, 2H), 5.82-5.70 (m, 2H), 4.97-4.85 (m, 4H), 2.20-2.00 (m, 4H), 2.00-1.75 (m, 4H). to give a colorless solution The mixture was slowly warmed up to room temperature After 20 minutes at room temperature the mixture was cooled to −78° C. The mixture was gradually warmed up to room temperature over 30 minutes The reaction was quenched by water the volatiles were evaporated The residue was partitioned between water and EtOAc The layers were separated the organic layer was washed with brine dried with Na2SO4 concentrated to a light yellow oil Purification up to 40% Et2O in hexane

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 6-bromo-1-indanone (0.5330 g, 2.52 mmol) in dry THF (10 mL) was added NaH (0.3380 g, 60% in a mineral oil, 8.45 mmol) at 0° C. under nitrogen. After being stirred for 10 min, 4-iodobut-1-ene (1.3450 g, 7.39 mmol) was added and then the mixture was stirred at ambient temperature for 20 h. The reaction mixture was cooled to 0° C., quenched with 1 N HCl, extracted with ethyl acetate, and dried over Na2SO4. After the solvents were evaporated, the residue was purified by chromatography on silica gel eluted with hexanes/ethyl acetate to afford 0.1304 g of 6-bromo-2,2-di(but-3-en-1-yl)-2,3-dihydro-1H-inden-1-one. LC-MS tR=2.33 min in 3 min chromatography, m/z 319, 321 (MH1); 1H NMR (400 MHz, CDCl3) δ 7.84 (s, 1H), 7.67 (d, J=8 Hz, 1H), 7.33 (d, J=8 Hz, 1H), 5.76-5.66 (m, 2H), 4.94-4.87 (m, 4H), 2.98 (s, 2H), 1.98-1.63 (m, 8H); 13C NMR (100 MHz, CDCl3) δ 209.23, 151.43, 138.85, 137.85, 137.54, 127.94, 126.75, 121.55, 114.81, 52.87, 37.28, 36.58, 28.54. the mixture was stirred at ambient temperature for 20 h quenched with 1 N HCl extracted with ethyl acetate dried over Na2SO4 After the solvents were evaporated the residue was purified by chromatography on silica gel eluted with hexanes/ethyl acetate

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 500 mL round-bottomed flask (t=g) was added crude 4-iodobut-1-ene (11.51 g, 63.2 mmol) in Et2O (100 mL) to give a colorless solution. After cooling to −78° C. under nitrogen, tBuLi (80 mL, 136 mmol) was added dropwise via syringe. The mixture was slowly warmed up to room temperature while stirring for 2 hours. After 20 minutes at room temperature, the mixture was cooled to −78° C. and ethyl 2,3-difluorobenzoate (4.28 mL, 28.7 mmol) was added dropwise via syringe. The mixture was gradually warmed up to room temperature over 30 minutes. The reaction was quenched by water and the volatiles were evaporated. The residue was partitioned between water and EtOAc. The layers were separated and the organic layer was washed with brine, dried with Na2SO4 and concentrated to a light yellow oil. Purification up to 40% Et2O in hexane afforded the desired product as a colorless oil: (1.41 g, 19%). 1H NMR (400 MHz, CDCl3) δ 7.31-7.22 (m, 1H), 7.10-7.03 (m, 2H), 5.82-5.70 (m, 2H), 4.97-4.85 (m, 4H), 2.20-2.00 (m, 4H), 2.00-1.75 (m, 4H). to give a colorless solution The mixture was slowly warmed up to room temperature After 20 minutes at room temperature the mixture was cooled to −78° C. The mixture was gradually warmed up to room temperature over 30 minutes The reaction was quenched by water the volatiles were evaporated The residue was partitioned between water and EtOAc The layers were separated the organic layer was washed with brine dried with Na2SO4 concentrated to a light yellow oil Purification up to 40% Et2O in hexane

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 6-bromo-1-indanone (0.5330 g, 2.52 mmol) in dry THF (10 mL) was added NaH (0.3380 g, 60% in a mineral oil, 8.45 mmol) at 0° C. under nitrogen. After being stirred for 10 min, 4-iodobut-1-ene (1.3450 g, 7.39 mmol) was added and then the mixture was stirred at ambient temperature for 20 h. The reaction mixture was cooled to 0° C., quenched with 1 N HCl, extracted with ethyl acetate, and dried over Na2SO4. After the solvents were evaporated, the residue was purified by chromatography on silica gel eluted with hexanes/ethyl acetate to afford 0.1304 g of 6-bromo-2,2-di(but-3-en-1-yl)-2,3-dihydro-1H-inden-1-one. LC-MS tR=2.33 min in 3 min chromatography, m/z 319, 321 (MH+); 1H NMR (400 MHz, CDCl3) δ 7.84 (s, 1H), 7.67 (d, J=8 Hz, 1H), 7.33 (d, J=8 Hz, 1H), 5.76-5.66 (m, 2H), 4.94-4.87 (m, 4H), 2.98 (s, 2H), 1.98-1.63 (m, 8H); 13C NMR (100 MHz, CDCl3) δ 209.23, 151.43, 138.85, 137.85, 137.54, 127.94, 126.75, 121.55, 114.81, 52.87, 37.28, 36.58, 28.54. the mixture was stirred at ambient temperature for 20 h quenched with 1 N HCl extracted with ethyl acetate dried over Na2SO4 After the solvents were evaporated the residue was purified by chromatography on silica gel eluted with hexanes/ethyl acetate