2,4-Pentadienoates

The intramolecular reaction oF allcenes with various O and N functional groups offers useful synthetic methods for heterocycles[13,14,166]. The reaction of unsaturated carboxylic acids affords lactones by either exo- or endo-cyclization depending on the positions of the double bond. The reaction of sodium salts of the 3-alkenoic acid 143 and 4-alkenoic acid 144 with Li2PdCl4 affords mostly five-membcrcd lactones in 30-40% yields[167]. Both 5-hexe-noic acid (145) and 4-hexenoic acid (146) are converted to five- or six-mem-bered lactones depending on the solvents and bases[168]. Conjugated 2,4-pentadienoic acid (147) is cyclized with Li2PdCl4 to give 2-pyrone (148) in water[i69]. 

Enamines have been observed to act both as dienophiles (46-48) and dienes (47,49) (dienamines in this case) in one-step, Diels-Alder type of 1,4 cycloadditions with acrylate esters and their vinylogs. This is illustrated by the reaction between l-(N-pyrrolidino)cyclohexene (34) and methyl t/-a i-2,4-pentadienoate (35), where the enamine acts as the dienophile to give the adduct 36 (47). In a competitive type of reaction, however, the... 

The value of a for the trans, tra s-5-substituted 2,4-pentadienoic acids suggests that the conformation in solution is the s-trans (between C and C ). Rough estimates give a value of a of about. 8 for the s-trans and of about 1.0 for... 

The Curtius rearrangement procedure described here is a modification of one reported by Winestock. The submitters have found this procedure to be considerably more reproducible when N,N-diisopropylethylamine is substituted for triethylamine. The procedure described for the preparation of trans-2,4-pentadienoic acid is a modification of an earlier one by Doebner. The submitters have found this method to give reproducibly higher yields, and to be more convenient, than other commonly used procedures for preparing this material. The use of dichloromethane as the extracting and crystallizing solvent greatly simplifies the isolation of polymer-free samples of the crystalline acid. 

Palladium catalyst, 59,160 Palladium(II) chloride, 59,161 Paraformaldehyde, 56,40 Pentachlorophenyllithium, 59, 72 frans-2,4-Pentadienoic acid, 59, 1 2,4-Pentadienoic acids, 59, 6... 

A complex naturally occurring amino acid 5-hydroxypiperazic acid (5HyPip) 100 was prepared by a multistep procedure that included Diels-Alder addition of 2,4-pentadienoic acid to phthalazinedione 83a as a first step (Scheme 24). Adduct 97 was esterified and oxidized with mercuric acetate to 98, which on hydrogenation over rhodium on alumina and subsequent hydrolysis provided a mixture of enantiomers from which the required enantiomer 99 was obtained by resolution with quinine. Its hydrazinolysis provided 100 [71JCS(C)514 77H119],... 

Yanovskaya and coworkers55 have reported rate constants for the alkaline hydrolysis of ethyl lruns,trans-4 -substi tuted 5-phenyl-2,4-pentadienoates in 60% aqueous dioxan giving the values X, log t, H, -2.60 Cl, -2.23 Br, -2.31 N02, -1.83 OMe, -2.61 NMe2, —3.00. Correlation with the CR equation gave as the best regression equation ... 

Structurally rather complicated target molecules can be synthesized with the aid of thi-olate 1,6-addition reactions to acceptor-substituted dienes as well. For example, a richly functionalized proline derivative with a 2,4-pentadienal side chain was converted into the corresponding 6-phenylthio-3-hexen-2-one derivative by 1,6-addition of phenylthiolate, treatment of the adduct with methyl lithium and oxidation (equation 46)127. The product was transformed into acromelic acid A, the toxic principle of clitocybe acromelalga ichimura. Similarly, the 1,6-addition reaction of cesium triphenylmethylthiolate to methyl 2,4-pentadienoate served for the construction of the disulfide bridge of the macrobicyclic antitumor depsipeptide FR-901,228128. 

Photolytic. The major photolysis and hydrolysis products identified in distilled water were pentachlorocyclopentenone and hexachlorocyclopentenone. In mineralized water, the products identified include cis- and /ra/3s-pentachlorobutadiene, tetrachlorobutenyne, and pentachloro-pentadienoic acid (Chou and Griffin, 1983). In a similar experiment, irradiation of hexachlorocyclopentadiene in water by mercury-vapor lamps resulted in the formation of 2,3,4,4,5-pentachloro-2-cyclopentenone. This compound hydrolyzed partially to hexachloroindenone (Butz et ah, 1982). Other photodegradation products identified include hexachloro-2-cyclopentenone and hexachloro-3-cyclopentenone as major products. Secondary photodegradation products reported include pentachloro-as-2,4-pentadienoic acid, Z- and A-pentachlorobutadiene, and tetrachloro-butyne (Chou et ah, 1987). In natural surface waters, direct photolysis of hexachlorobutadiene via sunlight results in a half-life of 10.7 min (Wolfe et al, 1982). 

The combination of cis-trans isomerism with iso-syndio and erythro-threo dispositions gives complex stractures as exemplified by the 1,4 polymers of 1-or 4-monosubstituted butadienes, such as 1,3-pentadiene (72, 73), and 2,4-pentadienoic acid (74, 75) and of 1,4-disubstituted butadienes, for example, sorbic acid (76). This last example is described in 32-35 (Scheme 6, rotated Fischer projection). Due to the presence of three elements of stereoisomerism for each monomer unit (two tertiary carbons and the double bond) these polymers have been classed as tritactic. Ignoring optical antipodes, eight stereoregular 1,4 structures are possible, four cis-tactic and four trans-tactic. In each series (cis, trans) we have two diisotactic and two disyndiotactic polymers characterized by the terms erythro and threo in accordance with the preceding explanation. It should be noted that here the erythro-threo relationship refers to adjacent substituents that belong to two successive monomer units. 

We have observed with the above catalyst system that both butadiene conversion and methyl 2, 4-pentadienoate selectivity increase when the catalyst is recycled. Over a series of seven recycle experiments, conversion increases from the low 20 s to 32.2 mole % and selectivity increases from the low 70 s to 83.2 mole % (See Table III.). Conversion and selectivity reach steady state after the third catalyst recycle. 

When methyl 5-amino-2,4-pentadienoates 496 were heated with an excess of acetaldehyde in a sealed tube, diastereomeric mixtures of 2,3-dihydro-67/-l,3-oxazine derivatives 497 and 498 were obtained instead of the expected [4- -2] cycloaddition products (Equation 58). Each condensation took place in a stereoselective way to give the /ra r-isomer 498 as the major product <1997CPB27>. 

Isosteric substitution of the C-2 hydrogen atom of valproic acid (12) with a fluorine atom affords 2-fluorovalproic acid (22), which causes significantly less hepatoxicity than valproic acid, although a reduction in anticonvulsant properties is also observed [59, 60]. The hepatoxicity of 12 involves hepatic cytochrome P450-mediated metabolism to its 4-ene metabolite (14), which undergoes further metabolism, specifically mitchondrial (3-oxidation, to provide ( )-2-propyl-2,4-pentadienoic add (23), a reactive electrophilic metabolite [59, 60]. 

Desaturation of alkyl groups. This novel reaction, which converts a saturated alkyl compound into a substituted alkene and is catalyzed by cytochromes P-450, has been described for the antiepileptic drug, valproic acid (VPA) (2-n-propyl-4-pentanoic acid) (Fig. 4.29). The mechanism proposed involves formation of a carbon-centered free radical, which may form either a hydroxy la ted product (alcohol) or dehydrogenate to the unsaturated compound. The cytochrome P-450-mediated metabolism yields 4-ene-VPA (2-n-propyl-4pentenoic acid), which is oxidized by the mitochondrial p-oxidation enzymes to 2,4-diene-VPA (2-n-propyl-2, 4-pentadienoic acid). This metabolite or its Co A ester irreversibly inhibits enzymes of the p-oxidation system, destroys cytochrome P-450, and may be involved in the hepatotoxicity of the drug. Further metabolism may occur to give 3-keto-4-ene-VPA (2-n-propyl-3-oxo-4-pentenoic acid), which inhibits the enzyme 3-ketoacyl-CoA thiolase, the terminal enzyme of the fatty acid oxidation system. 

Pentadienoic Acid 2.4-Dichloro-Irifluoro- ElOb, 580 (Educt)... 

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