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General procedure: A suspension of an appropriate aromatic aldehyde (1 eq.), and ylide I or II (1.3-1.5 eq.) inwater (4-10 mL) was stirred at 90 C for 0.5-24 h. Next, the heterogeneous reaction mixturewas cooled to room temperature, and the aqueous phase was extracted with DCM (3 10 mL).The solvent was evaporated under diminished pressure. Column chromatography (hexane-ethylacetate, or chloroform-methanol) of the residue gave the E-alkene as the major product.
General procedure: All aldehydes were previously prepared or purchased. Aldehyde 1 (5.0 mmol) was dissolved in THF (20 mL), and 1-(triphenylphosphoranylidene)-2-propanone (1.60 g, 5.0 mmol) was added. The mixture was allowed to stir at room temperature for 12 h. Solvent was removed under vacuum, and the residue was purified by flash column chromatography to provide 2, which was used directly in the next step, in almost quantitative yield.Compound 2 (2.0 mmol) and diethyl malonate (2.0 mmol) were dissolved in EtOH (5 mL), and a NaOEt solution (21 wt percent in ethanol; 1.50 mL, 4.0 mmol) was added. After being stirred for 12 h, 3 N aq NaOH (20 mL) was added, and stirring was continued for another 12 h. Aqueous 3 N HCl was added until the solution turned cloudy. Ether was used to extract the cloudy mixture until the aqueous layer was clear. The combined organic portions were combined and allowed to stir for 4 h until decarboxylation was complete. Heating might be required in some cases when decarboxylation was not complete at room temperature. The solvent was evaporated, and the crude product was then purified by recrystallization or flash chromatography. The CHD product was typically a white solid, obtained in about an 80percent yield, and had an Rf = 0.6 (dichloromethane/methanol = 8:1).
A solution of 1-hexyne (0.8 g, 10.0 mmol) in dry THF (50 mL) was magnetically stirred and cooled to -78 °C under N2 atmosphere This was followed by the slow addition of n-BuLi (1.6 M in THF, 10.0 mmol).The resulting reaction mixture was stirred at -78 C for 30 min, and then methyl chloroformate (1.3 g,14.0 mmol) was added. The reaction was stirred at -78 C for 30 min more and a saturated aqueoussolution of NH4Cl (20 mL) was added. The aqueous layer was separated and extracted with ethyl acetate(3 x 20 mL), and the combined organic layers were dried over Na2SO4, filtered and concentrated underreduced pressure. The crude product was purified by silica gel chromatography (ethyl acetate/hexane =5/95) to afford 7 (1.1 g, 8.0 mmol, 80percent yield). This was then treated with Ph3P and PhOH (0.4 eq. each)in PhMe at 50 C under an argon atmosphere to perform the alkyne to diene isomerization. After 1H NMRanalysis indicated that the reaction was completed, the mixture was cooled to room temperature andconcentrated under reduced pressure. The resulting mixture was purified by silica gel chromatography(CH2Cl2/hexane = 10/90, then ethyl acetate/hexane = 10/90) to afford the corresponding dienoate (1.0 g,89percent yield). This was dissolved in dry CH2Cl2 (50 mL) and DIBAL-H (2.5 eq.) was added at 0 C under aN2 atmosphere. After 45 min the reaction was quenched using MeOH/CH2Cl2 solution (1 mL/5 mL), andthe resulting mixture was washed with 1N aqueous HCl (3 x 20 mL), water (3 x 10 mL), brine (3 x 10mL), dried over Na2SO4, filtered and concentrated under reduced pressure to afford the correspondingdienol. This was used without further purification and dissolved in CH2Cl2 (50 mL), and reacted withMnO2 (8.0 eq.) at room temperature under an argon atmosphere. After TLC analysis indicated that thereaction was completed, the reaction mixture was filtered, concentrated under reduced pressure to affordthe crude 8 (0.6 g, 75percent yield). This was dissolved CHCl3 (50 mL) and 9 (1.5 eq.) was added, and thereaction mixture was heated to reflux. After TLC analysis indicated that the reaction was completed, thereaction mixture was concentrated under reduced pressure and purified by silica gel chromatography(ethyl acetate/hexane = 10/90) to afford 2o (0.5 g, 32percent overall yield).
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