1、Claisen 重排
将烯丙基乙烯基醚类加热，则发生[3,3]重排，高立体选择性的得 γ,δ-不饱和醛。
Claisen 重排法合成醛反应示例：
A 50-ml., round-bottomed flask equipped with a magnetic stirring bar and a 20-ml. calibration mark is charged with 970 mg. (2.51 mmoles) of cholest-4-en-3β-ol. Ethyl vinyl ether is di{attr}2129{/attr}ed into the flask to the 20-ml. mark. The mixture is stirred to effect solution efore 820 mg. (2.55 mmoles) of mercury(II) acetate is added to the reaction mixture. The flask is fitted with a reflux condenser connected to a gas-inlet tube and flushed with argon. The reaction mixture is then stirred and heated at reflux under a positive argon pressure for 17 hours. After the solution has cooled to room temperature, 0.062 ml. (1.1 mmoles) of glacial acetic acid is added, and stirring is continued for 3 hours. The reaction mixture is poured into a preshaken mixture of 150 ml. of petroleum ether and 50 ml. of 5% aqueous potassium hydroxide. The aqueous phase is extracted with 50 ml. of petroleum ether, and the combined extracts are washed with three 50-ml. portions of a 20% aqueous sodium chloride, dried over anhydrous sodium carbonate, filtered and evaporated at reduced pressure, giving 1.11 g. of an oil wh{attr}2164{/attr}, upon filtration through 5 g. of silica gel with 200 ml. of petroleum ether, affords 0.81 g. of the cholestenyl vinyl ether as a clear, colorless oil. If desired, crystallization of this oil from 10 ml. of acetone will give 0.74 g. (71%) of the vinyl ether as colorless prisms, m.p.55–56.5°.
Alternatively, the crude vinyl ether (0.81 g.) is transferred with petroleum ether into a 50-ml., round-bottomed flask fitted with a long gas-inlet tube. After the petroleum ether is removed at reduced pressure, the flask is filled with argon and heated under a positive argon pressure at 220–225° for 5 hours; little or no bubbling should occur. After cooling, the oil is chromatographed on 75 g. of silica gel using 10% diethyl ether in petroleum ether as the elution solvent The first 175 ml. of eluant contains side products and is discarded; elution with another 175 ml. of the solvent gives 0.45–0.55 g. (50–53% overall yield from cholest-4-en-3β-ol) of 5β-cholest-3-ene-5-acetaldehyde as white prisms, m.p. 66.5–68°.
2、酸催化下环氧化物重排
将环氧化物用酸处理则在开环时而发生重排得羰基化合物。
酸催化下环氧化物重排合成醛酮示例 1
In a 1-l. separatory funnel is placed a solution of 39.2 g. (0.2 mole) of trans-stilbene oxide in 450 ml. of reagent benzene. To the solution is added 13.2 ml. (0.1 mole) of boron trifluoride etherate. The solution is swirled, allowed to stand for 1 minute, and then washed with two 300-ml. portions of water. The organic layer is separated, and the benzene is removed by distillation. The residual crude aldehyde is purified by distillation under reduced pressure. The product, collected at 115–117°/0.6 mm., amounts to 29–32 g. (74–82%), n D 25 1.5875–1.5877.
酸催化下环氧化物重排合成醛酮示例 2
In a 1-l. separatory funnel is placed a solution of 38.6 g. (0.25 mole) of isophorone oxide in 400 ml. of reagent grade benzene. To the solution is added 20 ml. (0.16 mole) of boron trifluoride etherate. The resulting solution is mixed by swirling, allowed to stand for 30 minutes, then diluted with 100 ml. of ether and washed with 100 ml. of water. The organic layer is shaken for 1–2 minutes with a solution of 40 g. (1.0 mole) of sodium hydroxide in 200 ml. of water and then washed with a second 100–ml. portion of water. The combined aqueous solutions are cooled briefly in running water and then extracted with two 50-ml. portions of ether. The ethereal extracts are added to the benzene-ether solution, and the combined solution, after drying over anhydrous magnesium sulfate, is concentrated by distillation through a Claisen head. When the temperature of the distillate reaches about 80°, the residual liquid is fractionally distilled under reduced pressure. The yield of 2,4,4-trimethylcyclopentanone, b.p. 61–62°/21 mm., n D 28 1.4278–1.4288, is 17.7–19.8 g.(56–63%).
3、氧化法
醚的α-位易接受游离基反应，所以可因过氧化物、四醋酸铅、NBS 等氧化开裂得醛。
Into a 500-mL, two-necked, round-bottomed flask fitted with a gas inlet and a drying tube containing calcium chloride are placed methyl (S)-2-phthalimido-4-methylthiobutanoate（15.45 g, 52.7 mmol) and carbon tetrachloride (CCl 4 ) (160 mL). The mixture is magnetically stirred under nitrogen at room temperature, N-chlorosuccinimide (7.04 g, 52.7 mmol) is added in one portion, and the reaction mixture is stirred for 2 hr at room temperature. The resulting mixture is filtered through a sintered glass funnel with suction into a 1-L, three-necked, round-bottomed flask, and the collected succinimide (5.2 g) is rinsed with 100 mL of carbon tetrachloride . The three-necked flask containing the filtrate and rinse is equipped with a gas inlet, a stopper, and a cold water condenser. The condenser is equipped with a gas outlet that in turn is connected to a 500-mL Erlenmeyer flask containing 200 mL of sodium hypochlorite solution (commercial bleach) to scavenge volatile sulfur-containing by-products. Water (320
mL) is added in one portion, and nitrogen is bubbled through the solution at a rate of 2.4-3.0mL/sec for a period of 20 hr at room temperature. The resulting phases are separated using a separatory funnel, and the acidic aqueous phase is extracted with dichloromethane (2 × 50mL). The combined organic phases are washed with saturated aqueous sodium bicarbonate (100 mL), and water (100 mL) and then dried over sodium sulfate. The solution is filtered, and the filtrate is concentrated at reduced pressure using a rotary evaporator to give 14.0 g of crude product as a pale yellow oil. Chromatography of this oil over silica gel gives a white solid that is triturated at −15°C (ice-salt bath) using 20 mL of diethyl ether to provide 7.50-9.19 g (54-67%) of analytically pure aldehyde as a white solid (mp 52-103°C).
4、水解法合成醛酮
水解法合成醛酮示例 1 ：
cis-3-azido-4-oxo-2-azetidineacetaldehyde; A mixture of 500 mg (2.5 mmole) of cis-3-azido-2-(2,2-dimethoxyethyl)-4-oxoazetidine in 10 ml of 5percent HCl and 10 ml of dioxane was stirred at 35.deg. for 1/2 hour..; The mixture was diluted with water and extracted with 50 ml of benzene..; The aqueous phase was saturated with brine and extracted 10 times with 50 ml of ethyl acetate..; The ethyl acetate extract was dried over magnesium sulfate and evaporated to dryness..; The residue was titurated with ether to give the desired aldehyde, 235
mg (60percent), mp 73.deg.-78.deg.
水解法合成醛酮示例 2 ：
5-[4-(3-Oxopropoxy)benzyl]thiazolidine-2,4-dione; A solution of 6.30 g of 5-{4-[2-(1,3-dioxolan-2-yl) ethoxy]benzyl}thiazolidine-2,4-dione (prepared as described in Preparation 106) in 50 ml of a 4:1 mixture of acetic acid and water was stirred at 60.deg. C. for 6 hours..; At the end of this time, the reaction mixture was freed from the solvent by distillation under reduced pressure.; The resulting residue was purified by column chromatography through silica gel, using a 1:1 by volume mixture of hexane and ethyl acetate as the eluent, to give 2.20 g of the title compound, melting at 48.deg.-51.deg. C.
水解法合成醛酮示例 3 ：
A solution of 10.5 g of p-[trans-4-(3-methoxy-2-propenyl)cyclohexyl]benzonitrile in 200 ml of tetrahydrofuran/2N hydrochloric acid (vol. 4:1) was heated to reflux for 45 minutes while stirring..; The mixture was then partitioned three times in diethyl ether/water..; The organic extracts were washed twice with water, dried over magnesium sulphate, filtered and vaporated.; Chromatographic separation of the white, crystalline residue (9.9 g) on silica gel with ethyl acetate/petroleum ether (vol. 10:90 and 30:70) finally gave 9.4 g (95percent) of 3-[trans-4-(p-cyanophenyl)cyclohexyl]propionaldehyde as white crystals.
