hex-5-enal

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: The first step in the sequence in the pyrolysis of 3-hydroxy-1,5-hexadiene to prepare 5-hexenal which is reacted with malonic acid to form 2,7-octadienoic acid. The foregoing acid is esterified by treatment with diazomethane and the resulting methyl ester is reacted with the sodium salt of ethyl acetoacetate under the influence of sodium methoxide in a methanol menstruum to yield the sodium salt of methyl 6-(4pentenyl)-β-dihydroresorcylate. The dihydroresorcylate sodium salt is then brominated at low temperature to form methyl 3 -bromo-6-(4 -pentenyl)-β-dihydroresorcylate which is de-hydrobrominated by treatment with sodium ethoxide in an anhydrous ethanol menstruum to prepare ethyl 6-(4-pentenyl)-β-resorcylate. The foregoing resorcylate is reacted with benzyl chloride to yield ethyl 6-(4-pentenyl)-β-resorcylate dibenzyl ether which is treated with the sodium alcoholate of 4-penten-2 -ol to produce 4 -penten-2-yl 6-(4-pentenyl)-β -resorcylate dibenzyl ether. The foregoing compound is treated successively with 2,3-dimethyl-2-butylborane, carbon monoxide, sodium acetate solution, and hydrogen peroxide to form zearalanone dibenzyl ether. On Hydrogenation zearalanone dibenzyl ether is converted to (R,S)-zearalanone.

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

Procedure: To a ice-bath cooled solution of hex-5-enal (500 mg, 4.331 mmol) and trimethyl(trifluoromethyl)silane (0.74 g, 5.13 mmol, 1.2 equiv.) in THF (10 mL) was added tetrabutylammonium hydrofluoride (10 mg, 0.04 mmol). The ice bath was removed and the reaction progress was monitored via GCMS and 1H NMR. Upon complete transformation of the starting material the reaction mixture was treated with 2M HCl and stirred for an additional 2 h. Then, 50 mL of Et2O was introduced and the layers were separated. The aqueous fraction was additionally extracted with Et2O and the combined organic phases were washed sequentially with a saturated aqueous NaHCO3 solution, water, and brine. After drying with MgSO4 and filtration the solvent was removed under reduced pressure and the resultant crude residue was purified by column chromatography (silica gel, pentane/Et2O, v/v=8/2). Fractions containing the pure compound were collected and concentrated in vacuo to give 1,1,1-trifluorohept-6-en-2-ol (225 mg, 31% yield) as a yellow oil. The ice bath was removed Upon complete transformation of the starting material the reaction mixture was treated with 2M HCl Then, 50 mL of Et2O was introduced the layers were separated The aqueous fraction was additionally extracted with Et2O the combined organic phases were washed sequentially with a saturated aqueous NaHCO3 solution, water, and brine After drying with MgSO4 and filtration the solvent was removed under reduced pressure the resultant crude residue was purified by column chromatography (silica gel, pentane/Et2O, v/v=8/2) Fractions containing the pure compound were collected concentrated in vacuo

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

Procedure: Hex-5-enal (step 1) (solution in DCM, 25 mmol) was treated with 2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazine (Intermediate B) (3.94 g, 12.5 mmol). After stirring at room temp under nitrogen for 30 mins, sodium triacetoxyborohydride (3.18 g, 15.00 mmol) was added and stirring continued at room temperature overnight. Water (100 ml) was added to the reaction mixture. Once effervescence had ceased the organic portion was separated and dried by passing through a phase separating column. The solvent was removed under reduced pressure and the resulting brown oil was purified by flash column chromatography on silica eluting with 0-100% EtOAc in iso-hexane on a 80 g silca cartridge. The combined fractions were allowed to stand at room temperature for 2 days. The resulting suspension was collected by filtration and dried in a vacuum oven. The crude material was purified by chromatography on silica eluting with 0-50% EtOAc in iso-hexane to afford the title compound; stirring continued at room temperature overnight was separated dried separating column The solvent was removed under reduced pressure the resulting brown oil was purified by flash column chromatography on silica eluting with 0-100% EtOAc in iso-hexane on a 80 g silca cartridge to stand at room temperature for 2 days The resulting suspension was collected by filtration dried in a vacuum oven The crude material was purified by chromatography on silica eluting with 0-50% EtOAc in iso-hexane

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

Procedure: Hex-5-enal (step 1) (solution in DCM, 25 mmol) was treated with 2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazine (Intermediate B) (3.94 g, 12.5 mmol). After stirring at room temp under nitrogen for 30 mins, sodium triacetoxyborohydride (3.18 g, 15.00 mmol) was added and stirring continued at room temperature overnight. Water (100 ml) was added to the reaction mixture. Once effervescence had ceased the organic portion was separated and dried by passing through a phase separating column. The solvent was removed under reduced pressure and the resulting brown oil was purified by flash column chromatography on silica eluting with 0-100% EtOAc in iso-hexane on a 80 g silca cartridge. The combined fractions were allowed to stand at room temperature for 2 days. The resulting suspension was collected by filtration and dried in a vacuum oven. The crude material was purified by chromatography on silica eluting with 0-50% EtOAc in iso-hexane to afford the title compound; stirring continued at room temperature overnight was separated dried separating column The solvent was removed under reduced pressure the resulting brown oil was purified by flash column chromatography on silica eluting with 0-100% EtOAc in iso-hexane on a 80 g silca cartridge to stand at room temperature for 2 days The resulting suspension was collected by filtration dried in a vacuum oven The crude material was purified by chromatography on silica eluting with 0-50% EtOAc in iso-hexane

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

Procedure: Hex-5-enal (step 1) (solution in DCM, 25 mmol) was treated with 2,3-di-p-tolyl-5,6,7,8-tetrahydropyrido[2,3-b]pyrazine (Intermediate B) (3.94 g, 12.5 mmol). After stirring at room temp under nitrogen for 30 mins, sodium triacetoxyborohydride (3.18 g, 15.00 mmol) was added and stirring continued at room temperature overnight. Water (100 ml) was added to the reaction mixture. Once effervescence had ceased the organic portion was separated and dried by passing through a phase separating column. The solvent was removed under reduced pressure and the resulting brown oil was purified by flash column chromatography on silica eluting with 0-100% EtOAc in iso-hexane on a 80 g silca cartridge. The combined fractions were allowed to stand at room temperature for 2 days. The resulting suspension was collected by filtration and dried in a vacuum oven. The crude material was purified by chromatography on silica eluting with 0-50% EtOAc in iso-hexane to afford the title compound; stirring continued at room temperature overnight was separated dried separating column The solvent was removed under reduced pressure the resulting brown oil was purified by flash column chromatography on silica eluting with 0-100% EtOAc in iso-hexane on a 80 g silca cartridge to stand at room temperature for 2 days The resulting suspension was collected by filtration dried in a vacuum oven The crude material was purified by chromatography on silica eluting with 0-50% EtOAc in iso-hexane

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

Procedure: A solution of (R)-1-(4-isopropyl-2-thioxothiazolidin-3-yl)ethanone (11.8 g, 58.1 mmol) in dichloromethane (380 mL) under an atmosphere of nitrogen was cooled to −78° C., titanium tetrachloride (6.37 mL, 58.1 mmol) was added, and the mixture was stirred for 10 min. Diisopropylethylamine (10.12 mL, 58.1 mmol) was added, and the mixture was stirred for 1 h at −78° C. A 1 M solution of hex-5-enal (58.1 mL, 58.1 mmol) in dichloromethane was added, and the mixture was stirred for 2 h at −78° C. The reaction was quenched by addition of half-saturated NH4Cl (30 mL) and warmed to room temperature. The mixture was extracted twice with dichloromethane, and the organic phase was dried and evaporated to provide a residue. Chromatography on silica gel afforded the title compound (12.92 g, 74%). This procedure has also been carried out using the (R)-1-(4-benzyl-2-thioxothiazolidin-3-yl)ethanone auxiliary, with a similar result. the mixture was stirred for 1 h at −78° C the mixture was stirred for 2 h at −78° C The reaction was quenched by addition of half-saturated NH4Cl (30 mL) The mixture was extracted twice with dichloromethane the organic phase was dried evaporated to provide a residue

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

Procedure: A solution of (R)-1-(4-isopropyl-2-thioxothiazolidin-3-yl)ethanone (11.8 g, 58.1 mmol) in dichloromethane (380 mL) under an atmosphere of nitrogen was cooled to −78° C., titanium tetrachloride (6.37 mL, 58.1 mmol) was added, and the mixture was stirred for 10 min. Diisopropylethylamine (10.12 mL, 58.1 mmol) was added, and the mixture was stirred for 1 h at −78° C. A 1 M solution of hex-5-enal (58.1 mL, 58.1 mmol) in dichloromethane was added, and the mixture was stirred for 2 h at −78° C. The reaction was quenched by addition of half-saturated NH4Cl (30 mL) and warmed to room temperature. The mixture was extracted twice with dichloromethane, and the organic phase was dried and evaporated to provide a residue. Chromatography on silica gel afforded the title compound (12.92 g, 74%). This procedure has also been carried out using the (R)-1-(4-benzyl-2-thioxothiazolidin-3-yl)ethanone auxiliary, with a similar result. the mixture was stirred for 1 h at −78° C the mixture was stirred for 2 h at −78° C The reaction was quenched by addition of half-saturated NH4Cl (30 mL) The mixture was extracted twice with dichloromethane the organic phase was dried evaporated to provide a residue

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

Procedure: A solution of (R)-1-(4-isopropyl-2-thioxothiazolidin-3-yl)ethanone (11.8 g, 58.1 mmol) in dichloromethane (380 mL) under an atmosphere of nitrogen was cooled to −78° C., titanium tetrachloride (6.37 mL, 58.1 mmol) was added, and the mixture was stirred for 10 min. Diisopropylethylamine (10.12 mL, 58.1 mmol) was added, and the mixture was stirred for 1 h at −78° C. A 1 M solution of hex-5-enal (58.1 mL, 58.1 mmol) in dichloromethane was added, and the mixture was stirred for 2 h at −78° C. The reaction was quenched by addition of half-saturated NH4Cl (30 mL) and warmed to room temperature. The mixture was extracted twice with dichloromethane, and the organic phase was dried and evaporated to provide a residue. Chromatography on silica gel afforded the title compound (12.92 g, 74%). This procedure has also been carried out using the (R)-1-(4-benzyl-2-thioxothiazolidin-3-yl)ethanone auxiliary, with a similar result. the mixture was stirred for 1 h at −78° C the mixture was stirred for 2 h at −78° C The reaction was quenched by addition of half-saturated NH4Cl (30 mL) The mixture was extracted twice with dichloromethane the organic phase was dried evaporated to provide a residue

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

Procedure: A solution of (R)-1-(4-isopropyl-2-thioxothiazolidin-3-yl)ethanone (11.8 g, 58.1 mmol) in dichloromethane (380 mL) under an atmosphere of nitrogen was cooled to −78° C., titanium tetrachloride (6.37 mL, 58.1 mmol) was added, and the mixture was stirred for 10 min. Diisopropylethylamine (10.12 mL, 58.1 mmol) was added, and the mixture was stirred for 1 h at −78° C. A 1 M solution of hex-5-enal (58.1 mL, 58.1 mmol) in dichloromethane was added, and the mixture was stirred for 2 h at −78° C. The reaction was quenched by addition of half-saturated NH4Cl (30 mL) and warmed to room temperature. The mixture was extracted twice with dichloromethane, and the organic phase was dried and evaporated to provide a residue. Chromatography on silica gel afforded the title compound (12.92 g, 74%). This procedure has also been carried out using the (R)-1-(4-benzyl-2-thioxothiazolidin-3-yl)ethanone auxiliary, with a similar result. the mixture was stirred for 1 h at −78° C the mixture was stirred for 2 h at −78° C The reaction was quenched by addition of half-saturated NH4Cl (30 mL) The mixture was extracted twice with dichloromethane the organic phase was dried evaporated to provide a residue

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

Procedure: The first step in the sequence in the pyrolysis of 3-hydroxy-1,5-hexadiene to prepare 5-hexenal which is reacted with malonic acid to form 2,7-octadienoic acid. The foregoing acid is esterified by treatment with diazomethane and the resulting methyl ester is reacted with the sodium salt of ethyl acetoacetate under the influence of sodium methoxide in a methanol menstruum to yield the sodium salt of methyl 6-(4pentenyl)-β-dihydroresorcylate. The dihydroresorcylate sodium salt is then brominated at low temperature to form methyl 3 -bromo-6-(4 -pentenyl)-β-dihydroresorcylate which is de-hydrobrominated by treatment with sodium ethoxide in an anhydrous ethanol menstruum to prepare ethyl 6-(4-pentenyl)-β-resorcylate. The foregoing resorcylate is reacted with benzyl chloride to yield ethyl 6-(4-pentenyl)-β-resorcylate dibenzyl ether which is treated with the sodium alcoholate of 4-penten-2 -ol to produce 4 -penten-2-yl 6-(4-pentenyl)-β -resorcylate dibenzyl ether. The foregoing compound is treated successively with 2,3-dimethyl-2-butylborane, carbon monoxide, sodium acetate solution, and hydrogen peroxide to form zearalanone dibenzyl ether. On Hydrogenation zearalanone dibenzyl ether is converted to (R,S)-zearalanone.

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

Procedure: To a ice-bath cooled solution of hex-5-enal (500 mg, 4.331 mmol) and trimethyl(trifluoromethyl)silane (0.74 g, 5.13 mmol, 1.2 equiv.) in THF (10 mL) was added tetrabutylammonium hydrofluoride (10 mg, 0.04 mmol). The ice bath was removed and the reaction progress was monitored via GCMS and 1H NMR. Upon complete transformation of the starting material the reaction mixture was treated with 2M HCl and stirred for an additional 2 h. Then, 50 mL of Et2O was introduced and the layers were separated. The aqueous fraction was additionally extracted with Et2O and the combined organic phases were washed sequentially with a saturated aqueous NaHCO3 solution, water, and brine. After drying with MgSO4 and filtration the solvent was removed under reduced pressure and the resultant crude residue was purified by column chromatography (silica gel, pentane/Et2O, v/v=8/2). Fractions containing the pure compound were collected and concentrated in vacuo to give 1,1,1-trifluorohept-6-en-2-ol (225 mg, 31% yield) as a yellow oil. The ice bath was removed Upon complete transformation of the starting material the reaction mixture was treated with 2M HCl Then, 50 mL of Et2O was introduced the layers were separated The aqueous fraction was additionally extracted with Et2O the combined organic phases were washed sequentially with a saturated aqueous NaHCO3 solution, water, and brine After drying with MgSO4 and filtration the solvent was removed under reduced pressure the resultant crude residue was purified by column chromatography (silica gel, pentane/Et2O, v/v=8/2) Fractions containing the pure compound were collected concentrated in vacuo