Reactions of Enamines with Acrolein

A novel ring closure was discovered by Stork (6) in which the pyrrolidine enamine of a cycloalkanone reacts with acrolein. The scheme illustrates the sequence in the case of 1-pyrrolidino-l-cyclohexene, and the cyclopentane compound was found to undergo the reaction analogously. The procedure details the preparation of the bicyclo adduct and its cleavage to 4-cyclooctenecarboxylic acid. 

The procedure is the same as that described in Chapter 9, Section T for the preparation of the morpholine enamine of cyclohexanone. In place of morpholine, pyrrolidine (12.8 g, 0.18 mole) is used. The product is collected at 114-115715 mm, 1.5200. 

In a 500-ml three-necked flask equipped with a mechanical stirrer, a condenser, and a dropping funnel (drying tubes) is placed a solution of 15.1 g (0.01 mole) of 1-pyrrolo-dino-1-cyclohexene in 100 ml of dry dioxane. The solution is cooled to 0-5° in an ice bath, and acrolein (5.9 g, 0.0105 mole) is added with stirring over 20 minutes. The solution is then allowed to stir at room temperature overnight. Dioxane and excess acrolein are removed (rotary evaporator) and the residue is distilled at reduced pressure to give the product, bp 125-12770.5 mm, yield 75%. 

To a solution of 11.8 g of 2-A-pyrrolidylbicyclo[3.3.1]nonan-9-one in 25 ml of dry ether is added 25 g of methyl iodide in one portion. The solution is allowed to stand at room temperature for 2 hours, then filtered to remove the product. To the filtrate is added 5 g of methyl iodide and after 5 hours at room temperature, solid is again collected. A third crop is similarly obtained. The combined solids (approx. 17 g) are recrystallized from acetone-ethanol to give about 16 g of the methiodide, mp 220-222°. 

A mixture of 17 g of the methiodide and 32 ml of a 40 % aqueous potassium hydroxide solution is heated with stirring in a flask fitted with a condenser. The heating bath should be kept at 125-130°, and the heating should be continued for 5 hours. The cooled reaction mixture is then diluted with 30 ml of water and washed twice with 25-ml portions of ether. The aqueous layer is cautiously acidified in the cold with concentrated hydrochloric acid to a pH of about 2 and then extracted five times with 25-ml portions of ether. The combined extracts are washed twice with 10% sodium thiosulfate solution and are dried (magnesium sulfate). Removal of the solvent followed by distillation affords about 3 g of 4-cyclooctene-l-carboxylic acid, bp 125-12671-1 mm. The product may solidify and may be recrystallized by dissolution in a minimum amount of pentane followed by cooling in a Dry-Ice bath. After rapid filtration, the collected solid has mp 34-35°. 

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