(Z)-hex-4-en-3-one

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

Procedure: This compound was prepared from the condensation of Compound 793 (Structure 159 of Scheme XXXIII) and 2-hexen-4-one as yellow solid. 1H NMR (500 MHz, DMSO-d6) 12.1 (bs, 1H), 7.41 (dd, J=8.8, 2.4, 1H), 7.34 (d, J=8.8, 1H), 7.21 (bs, 1H), 6.92 (s, 1H), 4.37-4.28 (m, 1H), 3.12 (dd, J=17.1, 10.2, 1H), 2.53 (dd, J=17.1, 4.9, 1H), 2.37 (q, J=7.3, 2H), 1.12 (t, J=7.3, 3H), 1.12 (d, J=5.9, 3H).

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

Procedure: To a solution of sodium methoxide (162 grams, 3 moles) in 400 mls of anhydrous methanol is added, dropwise, 276 grams (3.2 moles) of methylcyanoacetate over a period of 1 hour at 60° C. with stirring. The resulting slurry is stirred at 60° C. for 10 minutes, whereupon 288 grams (3.0 moles) of 2-hexen-4-one is added over a 20 minute period. The resulting reaction mixture is stirred and heated at reflux for six hours, whereupon a distillation take-off condenser is affixed to the reaction flask and 240 mls of methanol are removed under reduced pressure (65 mm Hg). The reaction mixture is then cooled to room temperature and poured into 2 liters of water. Toluene (500 ml) is added and the mixture is transferred to a separatory funnel. The aqueous layer is removed and again extracted with toluene (500 mls). To the aqueous solution, 500 mls of 18% HCl are added with external cooling at 25° C., whereupon a solid material precipitates. The solid is filtered, dried and recrystallized from aqueous methanol to afford colorless needles of 3,6-dimethyl-2,4-dioxocyclohexanecarbonitrile (338 grams, 68.3% yield based on 2-hexen-4-one); m.p. 178°-179° C. The resulting product is represented by the following equilibrium mixture: ##STR21## is added over a 20 minute period The resulting reaction mixture heated at reflux for six hours, whereupon a distillation take-off condenser are removed under reduced pressure (65 mm Hg) poured into 2 liters of water Toluene (500 ml) is added the mixture is transferred to a separatory funnel The aqueous layer is removed again extracted with toluene (500 mls) To the aqueous solution, 500 mls of 18% HCl are added with external cooling at 25° C., whereupon a solid material precipitates The solid is filtered dried recrystallized from aqueous methanol

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

Procedure: To a solution of sodium methoxide (162 grams, 3 moles) in 400 mls of anhydrous methanol is added, dropwise, 276 grams (3.2 moles) of methylcyanoacetate over a period of 1 hour at 60° C. with stirring. The resulting slurry is stirred at 60° C. for 10 minutes, whereupon 288 grams (3.0 moles) of 2-hexen-4-one is added over a 20 minute period. The resulting reaction mixture is stirred and heated at reflux for six hours, whereupon a distillation take-off condenser is affixed to the reaction flask and 240 mls of methanol are removed under reduced pressure (65 mm Hg). The reaction mixture is then cooled to room temperature and poured into 2 liters of water. Toluene (500 ml) is added and the mixture is transferred to a separatory funnel. The aqueous layer is removed and again extracted with toluene (500 mls). To the aqueous solution, 500 mls of 18% HCl are added with external cooling at 25° C., whereupon a solid material precipitates. The solid is filtered, dried and recrystallized from aqueous methanol to afford colorless needles of 3,6-dimethyl-2,4-dioxocyclohexanecarbonitrile (338 grams, 68.3% yield based on 2-hexen-4-one); m.p. 178°-179° C. The resulting product is represented by the following equilibrium mixture: ##STR21## is added over a 20 minute period The resulting reaction mixture heated at reflux for six hours, whereupon a distillation take-off condenser are removed under reduced pressure (65 mm Hg) poured into 2 liters of water Toluene (500 ml) is added the mixture is transferred to a separatory funnel The aqueous layer is removed again extracted with toluene (500 mls) To the aqueous solution, 500 mls of 18% HCl are added with external cooling at 25° C., whereupon a solid material precipitates The solid is filtered dried recrystallized from aqueous methanol

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

Procedure: This compound was prepared from the condensation of Compound 793 (Structure 159 of Scheme XXXIII) and 2-hexen-4-one as yellow solid. 1H NMR (500 MHz, DMSO-d6) 12.1 (bs, 1H), 7.41 (dd, J=8.8, 2.4, 1H), 7.34 (d, J=8.8, 1H), 7.21 (bs, 1H), 6.92 (s, 1H), 4.37-4.28 (m, 1H), 3.12 (dd, J=17.1, 10.2, 1H), 2.53 (dd, J=17.1, 4.9, 1H), 2.37 (q, J=7.3, 2H), 1.12 (t, J=7.3, 3H), 1.12 (d, J=5.9, 3H).

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

Procedure: Prepared according to general procedure A from 4-hexen-3-one (70 μL, 0.61 mmol), cyclopentadiene (75 μL, 0.91 mmol), 70% aqueous perchloric acid (10.5 μL, 0.12 mmol) and (2S, 5S)-5-Benzyl-3-methyl-2-(5-methyl-furan-2-yl)-imidazolidin-4-one (30.7 mg, 0.12 mmol) in water (203 μL) for 22 hours at 0° C. Purification by silica gel chromatography (9:1 pentane:ether) provided the title compound as a colorless oil in 89% yield (88.7 mg, 0.54 mmol); 25:1 endo:exo, endo 90% ee. Product ratios were determined by GLC analysis (150° C., 23 psi); (1R, 2R, 3S, 4R) endo isomer tr=3.7 min, and (1S, 2S, 3R, 4S) endo isomer tr=3.6 min, exo isomers tr=3.4, 3.5 min. H NMR, 13C NMR, and IR data 1 were consistent with previously reported values (Zhu et al. (1997) J. Am. Chem. Soc. 119:3507-3512; Ahrendt et al. (2000) J. Am. Chem. Soc. 122:4243-4244). [α]D=+101.7 (c=1.0, CHCl3). Prepared Purification by silica gel chromatography (9:1 pentane:ether)

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

Procedure: Prepared according to general procedure A from 4-hexen-3-one (70 μL, 0.61 mmol), cyclopentadiene (75 μL, 0.91 mmol), 70% aqueous perchloric acid (10.5 μL, 0.12 mmol) and (2S, 5S)-5-Benzyl-3-methyl-2-(5-methyl-furan-2-yl)-imidazolidin-4-one (30.7 mg, 0.12 mmol) in water (203 μL) for 22 hours at 0° C. Purification by silica gel chromatography (9:1 pentane:ether) provided the title compound as a colorless oil in 89% yield (88.7 mg, 0.54 mmol); 25:1 endo:exo, endo 90% ee. Product ratios were determined by GLC analysis (150° C., 23 psi); (1R, 2R, 3S, 4R) endo isomer tr=3.7 min, and (1S, 2S, 3R, 4S) endo isomer tr=3.6 min, exo isomers tr=3.4, 3.5 min. H NMR, 13C NMR, and IR data 1 were consistent with previously reported values (Zhu et al. (1997) J. Am. Chem. Soc. 119:3507-3512; Ahrendt et al. (2000) J. Am. Chem. Soc. 122:4243-4244). [α]D=+101.7 (c=1.0, CHCl3). Prepared Purification by silica gel chromatography (9:1 pentane:ether)

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

Procedure: This compound was prepared from the condensation of Compound 793 (Structure 159 of Scheme XXXIII) and 2-hexen-4-one as yellow solid. 1H NMR (500 MHz, DMSO-d6) 12.1 (bs, 1H), 7.41 (dd, J=8.8, 2.4, 1H), 7.34 (d, J=8.8, 1H), 7.21 (bs, 1H), 6.92 (s, 1H), 4.37-4.28 (m, 1H), 3.12 (dd, J=17.1, 10.2, 1H), 2.53 (dd, J=17.1, 4.9, 1H), 2.37 (q, J=7.3, 2H), 1.12 (t, J=7.3, 3H), 1.12 (d, J=5.9, 3H).

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

Procedure: This compound was prepared from the condensation of Compound 793 (Structure 159 of Scheme XXXIII) and 2-hexen-4-one as yellow solid. 1H NMR (500 MHz, DMSO-d6) 12.1 (bs, 1H), 7.41 (dd, J=8.8, 2.4, 1H), 7.34 (d, J=8.8, 1H), 7.21 (bs, 1H), 6.92 (s, 1H), 4.37-4.28 (m, 1H), 3.12 (dd, J=17.1, 10.2, 1H), 2.53 (dd, J=17.1, 4.9, 1H), 2.37 (q, J=7.3, 2H), 1.12 (t, J=7.3, 3H), 1.12 (d, J=5.9, 3H).

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

Procedure: This compound was prepared from the condensation of Compound 793 (Structure 159 of Scheme XXXIII) and 2-hexen-4-one as yellow solid. 1H NMR (500 MHz, DMSO-d6) 12.1 (bs, 1H), 7.41 (dd, J=8.8, 2.4, 1H), 7.34 (d, J=8.8, 1H), 7.21 (bs, 1H), 6.92 (s, 1H), 4.37-4.28 (m, 1H), 3.12 (dd, J=17.1, 10.2, 1H), 2.53 (dd, J=17.1, 4.9, 1H), 2.37 (q, J=7.3, 2H), 1.12 (t, J=7.3, 3H), 1.12 (d, J=5.9, 3H).

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

Procedure: This compound was prepared from the condensation of Compound 793 (Structure 159 of Scheme XXXIII) and 2-hexen-4-one as yellow solid. 1H NMR (500 MHz, DMSO-d6) 12.1 (bs, 1H), 7.41 (dd, J=8.8, 2.4, 1H), 7.34 (d, J=8.8, 1H), 7.21 (bs, 1H), 6.92 (s, 1H), 4.37-4.28 (m, 1H), 3.12 (dd, J=17.1, 10.2, 1H), 2.53 (dd, J=17.1, 4.9, 1H), 2.37 (q, J=7.3, 2H), 1.12 (t, J=7.3, 3H), 1.12 (d, J=5.9, 3H).

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

Procedure: To a solution of sodium methoxide (162 grams, 3 moles) in 400 mls of anhydrous methanol is added, dropwise, 276 grams (3.2 moles) of methylcyanoacetate over a period of 1 hour at 60° C. with stirring. The resulting slurry is stirred at 60° C. for 10 minutes, whereupon 288 grams (3.0 moles) of 2-hexen-4-one is added over a 20 minute period. The resulting reaction mixture is stirred and heated at reflux for six hours, whereupon a distillation take-off condenser is affixed to the reaction flask and 240 mls of methanol are removed under reduced pressure (65 mm Hg). The reaction mixture is then cooled to room temperature and poured into 2 liters of water. Toluene (500 ml) is added and the mixture is transferred to a separatory funnel. The aqueous layer is removed and again extracted with toluene (500 mls). To the aqueous solution, 500 mls of 18% HCl are added with external cooling at 25° C., whereupon a solid material precipitates. The solid is filtered, dried and recrystallized from aqueous methanol to afford colorless needles of 3,6-dimethyl-2,4-dioxocyclohexanecarbonitrile (338 grams, 68.3% yield based on 2-hexen-4-one); m.p. 178°-179° C. The resulting product is represented by the following equilibrium mixture: ##STR21## is added over a 20 minute period The resulting reaction mixture heated at reflux for six hours, whereupon a distillation take-off condenser are removed under reduced pressure (65 mm Hg) poured into 2 liters of water Toluene (500 ml) is added the mixture is transferred to a separatory funnel The aqueous layer is removed again extracted with toluene (500 mls) To the aqueous solution, 500 mls of 18% HCl are added with external cooling at 25° C., whereupon a solid material precipitates The solid is filtered dried recrystallized from aqueous methanol

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

Procedure: To a solution of sodium methoxide (162 grams, 3 moles) in 400 mls of anhydrous methanol is added, dropwise, 276 grams (3.2 moles) of methylcyanoacetate over a period of 1 hour at 60° C. with stirring. The resulting slurry is stirred at 60° C. for 10 minutes, whereupon 288 grams (3.0 moles) of 2-hexen-4-one is added over a 20 minute period. The resulting reaction mixture is stirred and heated at reflux for six hours, whereupon a distillation take-off condenser is affixed to the reaction flask and 240 mls of methanol are removed under reduced pressure (65 mm Hg). The reaction mixture is then cooled to room temperature and poured into 2 liters of water. Toluene (500 ml) is added and the mixture is transferred to a separatory funnel. The aqueous layer is removed and again extracted with toluene (500 mls). To the aqueous solution, 500 mls of 18% HCl are added with external cooling at 25° C., whereupon a solid material precipitates. The solid is filtered, dried and recrystallized from aqueous methanol to afford colorless needles of 3,6-dimethyl-2,4-dioxocyclohexanecarbonitrile (338 grams, 68.3% yield based on 2-hexen-4-one); m.p. 178°-179° C. The resulting product is represented by the following equilibrium mixture: ##STR23## is added over a 20 minute period The resulting reaction mixture heated at reflux for six hours, whereupon a distillation take-off condenser are removed under reduced pressure (65 mm Hg) poured into 2 liters of water Toluene (500 ml) is added the mixture is transferred to a separatory funnel The aqueous layer is removed again extracted with toluene (500 mls) To the aqueous solution, 500 mls of 18% HCl are added with external cooling at 25° C., whereupon a solid material precipitates The solid is filtered dried recrystallized from aqueous methanol