Diene acid

Now consider strategy b. How would you make the diene acid B, what reagent would you use for the carbene synthon, and how do you rate the chances of this route ... 

The wM-diacetate 363 can be transformed into either enantiomer of the 4-substituted 2-cyclohexen-l-ol 364 via the enzymatic hydrolysis. By changing the relative reactivity of the allylic leaving groups (acetate and the more reactive carbonate), either enantiomer of 4-substituted cyclohexenyl acetate is accessible by choice. Then the enantioselective synthesis of (7 )- and (S)-5-substituted 1,3-cyclohexadienes 365 and 367 can be achieved. The Pd(II)-cat-alyzed acetoxylactonization of the diene acids affords the lactones 366 and 368 of different stereochemistry[310]. The tropane alkaloid skeletons 370 and 371 have been constructed based on this chemoselective Pd-catalyzed reactions of 6-benzyloxy-l,3-cycloheptadiene (369)[311]. 

A similar sequence of reactions has been shown to take place with the dienamine derived from isophorone and morpholine (77). Reaction of this enamine with trichloroacetic acid gave a trichloromethyl derivative which was not isolated but which undergoes rearrangement and hydrolysis with base to give the diene acid (210). 

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. 

Corey s retrosynthetic concept (Scheme 9) is based on two key transformations a cationic cyclization and an intramolecular Diels-Alder (IMDA) reaction. Thus, cationic cychzation of diene 50 would give a precursor 49 for epf-pseudo-pteroxazole (48), which could be converted into 49 via nitration and oxazole formation. Compound 50 would be obtained by deamination of compound 51 and subsequent Wittig chain elongation. A stereocontroUed IMDA reaction of quinone imide 52 would dehver the decaline core of 51. IMDA precursor 52 should be accessible by amide couphng of diene acid 54 and aminophenol 53 followed by oxidative generation of the quinone imide 52 [28]. 

The actual synthesis (Scheme 10) commenced with the couphng of diene acid 54 and aminophenol 53 to provide diene amide 55. In situ generation of quinone monoimide 52 under oxidative conditions and subsequent intramolecular Diels-Alder (IMDA) reaction furnished an 8 1 mixture of endo/exo... 

CHC13 CC14 acid diene acid carpane ... 

Irradiation of 6,6-dimethyl-2,4-cyclohexadienene (Formula 92) (R = It = Me) in aqueous ether gives the diene acid (Formula 93) (R = R = Me) (48), and in similar fashion 4-methyl-6,6-diacetoxy-2,4-cyclo-hexadienone (Formula 98) gives the acid (Formula 99) (48). Irradiation... 

The dienone (Formula 119) is cleaved to the diene acid (Formula 120) on irradiation in ether containing water (50). 

Dehydration of castor oil and of castor acids gives products enriched in diene acids, some with conjugated unsaturation. These products are valuable alternatives to drying oils such as tung oil. 

In a similar manner, the diacetates from cyclic dienes were enzymatically hydrolyzed and transformed to the enantiomers of diene acids 50 [71]. The diene acids from the seven-membered ring were subsequently used in intramolecular cis- and trans-1,4-acetoxylactonizations (cf. Scheme 8-14), leading to four different isomers of enantiomerically pure lactones. 

The first enantioselective formal total synthesis of paeonilactone A was reported by J.E. Backvall who used a palladium(ll)-catalyzed 1,4-oxylactonization of a conjugated diene as the key step. The lactonization precursor diene acid was obtained from an enantiopure dimethyl malonate derivative via sequential Krapcho decarboxylation and ester hydrolysis. 

Scheme 13 Ring-closing metathesis of diene acid 45...

The most convenient source of conjugated diene acids is via the dehydration of castor oil (Section 3.3.4) by heating ( 250°C) in the presence of an acidic catalyst. The product is complex and the dienes produced from ricinoleate are both conjugated (mainly A9,ll) and non-conjugated (mainly A9,12) in the proportion 1 3 or 4. Several configurational isomers are produced and double-bond migration complicates the product further. Alkaline isomerization of linoleic-rich oils also produces conjugated dienes (A9,ll and A10,12) but these processes have not proved to be of commercial value. 

C20 cyclic fatty acids of a slightly different type are produced by diene synthesis from a Cis conjugated diene acid and ethene. 

Monoene acids produce mainly acyclic (40%) and monocyclic (55%) dimers but diene acids furnish monocyclic (55%) and bicyclic (40%) dimers. Tall oil fatty acids, containing both oleic and linoleic acid, are frequently used to produce dimers on an industrial scale. A typical product contains 80% dimer acids and 20% trimer acids with only a trace of monomer. 

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