5-溴戊-1-烯

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 2-butyl-5-(methoxymethoxy)-1-indanone (1.54 g, 6.2 mmol) in anhydrous N,N-dimethylformamide (DMF, 5 mL) was added to a suspension of sodium hydride (372 mg of a 60% dispersion in mineral oil, 9.3 mmol) in DMF (5 mL). The mixture was diluted with more DMF (2 mL, used to rinse in the indanone solution), placed under a nitrogen atmosphere, and stirred at room temperature for 25 minutes. 5-Bromo-1-pentene (1.47 mL, 12.4 mmol) was then added over 5 minutes, during which time the mixture clarified. After stirring at room temperature for an additional 5 hours, the mixture was quenched with saturated NH4Cl, dried over MgSO4, filtered through a pad of silica, and concentrated under vacuum to afford an oil. The crude product was purified by Biotage™ (Charlottesville, Va.) flash chromatography on a 40S (4.0×7.0 cm) silica gel column, eluting with 19:1 hexanes-EtOAc. The product-containing fractions were evaporated under vacuum to afford 2-butyl-5-(methoxymethoxy)-2-(4-pentenyl)-1-indanone as an oil. to rinse in the indanone solution), After stirring at room temperature for an additional 5 hours the mixture was quenched with saturated NH4Cl dried over MgSO4 filtered through a pad of silica concentrated under vacuum to afford an oil The crude product was purified by Biotage™ (Charlottesville, Va.) flash chromatography on a 40S (4.0×7.0 cm) silica gel column eluting with 19:1 hexanes-EtOAc The product-containing fractions were evaporated under vacuum

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 5-methoxy-1-indanone (2.5 g, 15.4 mmol) in DMF (20 mL) at rt was added NaH (1.8 g, 61% in oil, 46.2 mmol) and 5-bromo-1-pentene (5.48 mL, 46.2 mmol). After 6 h at rt, the solution was diluted with CH2Cl2 and quenched with saturated aqueous NH4Cl. The slurry was dried with MgSO4 and filtered through a plug of silica and rinsed with 10% EtOAc in hexanes. The filtrate was concentrated and provided crude 2,2-di(4-pentenyl)-5-methoxy-1-indanone. quenched with saturated aqueous NH4Cl The slurry was dried with MgSO4 filtered through a plug of silica rinsed with 10% EtOAc in hexanes The filtrate was concentrated

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirring solution of 5-bromo-pentene (6.0 g, 0.040 mol) in DMF (30 mL) was added K2CO3 (4.7 g, 0.034 mol) and potassium phthalimide (6.21 g, 0.033 mmol) and the reaction mixture was heated at 100° C. for 1 hr. The reaction mixture was cooled to room temperature, and water (50 mL) was added. The aqueous layer was then extracted with ethyl acetate (2×50 mL), and the combined organic layers were washed with 5% aq. NaHCO3 (2×20 mL), brine (30 mL) and dried over Na2SO4. Filtration and solvent evaporation gave an oil, which was purified by flash chromatography (silica gel/hexanes:ethyl acetate 0-35%) to yield the desired 2-(pent-4-enyl)-isoindoline-1,3-dione as a solid (6.36 g, 0.029 mmol, 72.5% yield): MS m/e [M+H]+ calcd 216.1, found 216.1; NMR (250 MHz, DMSO-d6) δ 7.79-7.95 (m, 4 H), 5.70-5.91 (m, 1 H), 4.90-5.11 (m, 2 H), 3.58 (t, 2 H), 1.98-2.10 (m, 2H), 1.59-1.78 (m, 2 H). The reaction mixture was cooled to room temperature The aqueous layer was then extracted with ethyl acetate (2×50 mL) the combined organic layers were washed with 5% aq. NaHCO3 (2×20 mL), brine (30 mL) dried over Na2SO4 Filtration and solvent evaporation gave an oil, which was purified by flash chromatography (silica gel/hexanes:ethyl acetate 0-35%)

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirring solution of 5-bromo-pentene (6.0 g, 0.040 mol) in DMF (30 mL) was added K2CO3 (4.7 g, 0.034 mol) and potassium phthalimide (6.21 g, 0.033 mmol) and the reaction mixture was heated at 100° C. for 1 hr. The reaction mixture was cooled to room temperature, and water (50 mL) was added. The aqueous layer was then extracted with ethyl acetate (2×50 mL), and the combined organic layers were washed with 5% aq. NaHCO3 (2×20 mL), brine (30 mL) and dried over Na2SO4. Filtration and solvent evaporation gave an oil, which was purified by flash chromatography (silica gel/hexanes:ethyl acetate 0-35%) to yield the desired 2-(pent-4-enyl)-isoindoline-1,3-dione as a solid (6.36 g, 0.029 mmol, 72.5% yield): MS m/e [M+H]+ calcd 216.1, found 216.1; NMR (250 MHz, DMSO-d6) δ 7.79-7.95 (m, 4 H), 5.70-5.91 (m, 1 H), 4.90-5.11 (m, 2 H), 3.58 (t, 2 H), 1.98-2.10 (m, 2 H), 1.59-1.78 (m, 2 H). The reaction mixture was cooled to room temperature The aqueous layer was then extracted with ethyl acetate (2×50 mL) the combined organic layers were washed with 5% aq. NaHCO3 (2×20 mL), brine (30 mL) dried over Na2SO4 Filtration and solvent evaporation gave an oil, which was purified by flash chromatography (silica gel/hexanes:ethyl acetate 0-35%)

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirring solution of 5-bromo-pentene (6.0 g, 0.040 mol) in DMF (30 mL) was added K2CO3 (4.7 g, 0.034 mol) and potassium phthalimide (6.21 g, 0.033 mmol) and the reaction mixture was heated at 100° C. for 1 hr. The reaction mixture was cooled to room temperature, and water (50 mL) was added. The aqueous layer was then extracted with ethyl acetate (2×50 mL), and the combined organic layers were washed with 5% aq. NaHCO3 (2×20 mL), brine (30 mL) and dried over Na2SO4. Filtration and solvent evaporation gave an oil, which was purified by flash chromatography (silica gel/hexanes:ethyl acetate 0-35%) to yield the desired 2-(pent-4-enyl)-isoindoline-1,3-dione as a solid (6.36 g, 0.029 mmol, 72.5% yield): MS m/e [M+H]+ calcd 216.1. found 216.1; NMR (250 MHz, DMSO-d6) δ 7.79-7.95 (m, 4H), 5.70-5.91 (m, 1H), 4.90-5.11 (m, 2H), 3.58 (t, 2H), 1.98-2.10 (m, 2H), 1.59-1.78 (m, 2H). The reaction mixture was cooled to room temperature The aqueous layer was then extracted with ethyl acetate (2×50 mL) the combined organic layers were washed with 5% aq. NaHCO3 (2×20 mL), brine (30 mL) dried over Na2SO4 Filtration and solvent evaporation gave an oil, which was purified by flash chromatography (silica gel/hexanes:ethyl acetate 0-35%)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: FIG. 5 illustrates the scheme for the synthesis of field-active (2S,7S)2,7-nonanediyl dibutyrate (14): S-propylene oxide (6) (Fluka Chemika-Biochemika, Buchs, Switzerland) was coupled at −20° C. with Grignard reagent 7 in the presence of 0.1 equivalents of a CuI catalyst. Resulting (2S)-8-octen-2-ol (8) was oxidized by m-chloroperoxybenzoic acid (Aldrich Chemical Co.) to the terminal epoxide 9. Hydrolytic kinetic resolution of 9 with Co(II) salen (Jacobsen's) catalyst (R,R)N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminoc (10) (Aldrich Chemical Co.) (24, 25) afforded 2(R),7(S)-1,2-epoxy-7-hydroxyoctane (11), which was separated from unwanted 1,2(S),7(S)-octanetriol (12) by silica flash chromatography [hexane: ether (1:1), then ether as eluents]. Ring opening of 11 with excess of methylmagnesium bromide (Aldrich Chemical Co.) and catalytic amounts of Cul yielded (2S,7S)-2,7-nonanediol (13) which was esterified to (2S,7S)-2,7-nonanediol dibutyrate [14; 77% enantiomeric excess (ee) as determined by chiral GC; 37% overall yield]. GC-MS and NMR data of 14 were consistent with those of 5 (FIG. 4). The remaining 3 stereoisomers of diester 5 were synthesized from (S)- or (R)-propylene oxide (Fluka Chemika-Biochemika) and 5-bromo-pentene (Aldrich Chemical Co.), again by hydrolytic kinetic resolution of terminal epoxide intermediates, with ee of end products ranging between 73-85%.