Ethyl-4-methyl-3,5-hexadienoate

The synthesis of chaparrinone and other quassinoids (naturally occurring substances with antileukemic activity) is another striking example [16a-c]. The key step of synthesis was the Diels-Alder reaction between the a,/l-unsaturated ketoaldehyde 1 (Scheme 6.1) with ethyl 4-methyl-3,5-hexadienoate 2 (R = Et). In benzene, the exo adduct is prevalent but it does not have the desired stereochemistry at C-14. In water, the reaction rate nearly doubles and both the reaction yield and the endo adduct increase considerably. By using the diene acid 2 (R = H) the reaction in water is 10 times faster than in organic solvent and the diastereoselectivity and the yield are satisfactory. The best result was obtained with diene sodium carboxylate 2 (R = Na) when the reaction is conducted 2m in diene the reaction is complete in 5h and the endo adduct is 75% of the diaster-eoisomeric reaction mixture. 

Pineapple Allyl capruale, cyclohexylacetaie. cyclohexylbutyrate, cyclohexylptopionate. 2-nonylenate, phenoxyacetate Benzyl formate Bomyl acetate n-Bulyl acetate Butyl isobutyrate Cinnamyl acetate Decanal dimethyl acetal Ethyl butyrate, hexadienoate. phenoxyacetate Hexyl butyrate 2-Methylallyl capruale Methyl heia-methy Ipropionaie Methyl undecylate Propyl isobutyrate. 

Melon Cinnamaldehyde Ethyl hexadienoate Methyl amyl ketone Octyl butvrate. 

Hexadienoate Ethyl 3-Ethyl- 2786 Methyl- 3-Propyl- 2785 Octane... 

The oldest syntheses of chrysanthemates are those starting from 2,5-dimethyl-2,4-hexadiene (238). There have been more papers on the use of rhodium or antimony to catalyze the addition of diazoacetate and chiral copper complexes to create asymmetry during the addition (see Vol. 4, p. 482, Refs. 219-222). The problem with this route is to avoid the use of diazo compounds. An old synthesis of Corey and Jautelat used the ylide addition of a sulfurane to a suitable precursor (in this case a C3 unit was added to methyl 5-methyl-2,4-hexadienoate, 239), and a recent paper gives details about the addition of ethyl dimethylsulfuranylideneacetate to 2,5-dimethyl-4-hexen-3-one (240). This led exclusively to the tran -isomer 241, from which ethyl trans-chrysanthemate (185, R = Et) was made. Other ylide additions are mentioned below. 

M. P. S. Ishar, R. P. Gandhi. Tetrahedron 47, 2211 (1991) analogous results with ethyl 4-elhyl-2,3-hexadicnoate and ethyl 4-methyl-2,3-hexadienoate. 

Ethyl 3,4-pentadienoate, 203 - (S) Ethyl 3,4-hexadienoate, 204 - (0) 2,2-Dimethyl-3,4-pentadienal, 204 - (7) 3-Hethyl-l,2-butadienyl acetate (l-acetoxy-3-methyl-l,2-butadiene), 205... 

A solution of -butyllithium (19.57 mL, 2.5 M in tetrahydrofuran, 48.9 mmol) is added at 0 °C to a solution of diisopropylamine (6.85 mL, 48.9 mmol) in tetrahydrofuran (100 mL). After 10 min, the reaction is cooled to -78 °C followed by dropwise addition of tricarbonyl(methyl 3,5-hexadienoate)iron (12.39 g, 46.6 mmol) in tetrahydrofuran (5 mL). The reaction mixture is kept at this temperature for 20 min. After the addition of methyl iodide (10 mL, 22.7 g, 159.9 mmol), the mixture is allowed to warm to room temperature over 1 h and quenched with a saturated solution of ammonium chloride. The aqueous layer is extracted with ethyl acetate (3 x 50 mL). The combined organic layers are washed with 1 N phosphoric acid (2 x 40 mL) and saturated aqueous sodium hydrogen carbonate (1 X 40 mL), then dried with magnesium sulfate and concentrated. The resulting oil is purified by chromatography (hexane/ethyl acetate, 19 1) to afford the a-methylated (r -diene)iron complex as a yellow solid mp 43-44 °C Rf = 0.53 (hexane/ethyl acetate, 9 1) dr 94 4 9.46 g (72%). ... 

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