3.5- Hexadienoic acid Diels-Alder reactions

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. 

Much effort has been directed at developing aqueous Diels-Alder reactions toward the syntheses of a variety of complex natural products. Grieco employed micellar catalysis and pure water as the solvent for the Diels-Alder reaction of dienecarboxylate with a variety of dienophiles. For example, when the Diels-Alder reaction in Scheme 12.3 was carried out in water, a higher reaction rate and reversal of the selectivity were observed, compared with the same reaction in a hydrocarbon solvent (Scheme 12.3).81 Similarly, the reaction of 2,6-dimethylbenzoquinone with sodium ( )-3,5-hexadienoate (generated in situ by the addition of 0.95 equiv sodium bicarbonate to a suspension of the precursor acid in water) proceeded for 1 hour to give a 77% yield of the adduct... 

The alkylation procedure can be used to prepare a wide variety of 2-substituted-2,4-cyclohexadienones, 2,3 5i 6 which are useful starting materials. The compounds can serve either as dienes or dienophiles7 in the Diels-Alder reaction and can be opened photochemically to yield substituted A3,5-hexadienoic acids.8... 

In an early application, the aqueous Diels-Alder reaction of diene carboxy-lates was used to effect a very concise synthesis of the vemolepin precursor 5.2 [60]. This compound had previously been prepared by Schlessinger via another route in 11 steps from ethyl crotonate [61]. Reaction of the substituted methacrolein 5.3 with sodium ( )-3,5-hexadienoate (5.4) in water proceeded at 50 C to give the Diels-Alder endo adduct 5.5 along with a minor amount of the exo adduct (not shown) quantitatively in a ratio of 10/1 (Scheme 1.4). Sodium borohydride was added directly to this reaction mixture to produce the 6-hydroxycarboxylate 5.6, which lactonized spontaneously upon acidic workup. This one-pot operation resulted in the isolation of vemolepin AB-ring... 

Under analogous aqueous reaction conditions, the sodium salts of ( )-3,S-hexadienoic, ( , )-6-meth-oxy-3,5-hexadienoic and ( )-4,6-heptadienoic acid underwent high-yielding [4 + 2] cycloadditions to a variety of dienophiles, e.g. to the Ca-substituted enal (248) (Scheme 58). The crude Diels-Alder... 

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