1.3- Dienoates

The cyclic 2,4-dienoate 184, formed by the Pd-catalyzed cyclization of the 1,6-enyne 183, reacted with 154 to form the azulene derivative 185[118], The 3-methylenepyrrolidine 188 is formed by the reaction of the Zn reagent 186 with the chiral imine 187 with high diastereomeric excess. The structure of the allylic ethers is important for obtaining high diastereoselectivity[l 19],... 

Carbonylation of propargylic carbonates proceeds under mild neutral conditions (50 °C, I-10 atm) using Pd(OAc)2 and Ph ,P as a catalyst, yielding the 2,3-alkadienoates 18 in good yields[9,10]. The 2.3-alkadienoates isomerize to 2,4-dienoates during the reaction depending on the solvents and reaction time. 2-Decynyl methyl carbonate is converted into methyl 2-heptyl-2,3-butadienoate (19) in 82% yield. 

These conditions gave excellent selectivity for an external methyl dienoate in the presence of a more hindered internal dienoate during a... 

Chemical Name 9a-FIuoro-11(3-17,21 -trihydroxy-160 -methyIpregna-1,4-diene-3,20-dione-21 -(octadeca-cis-9,cis-12-dienoate)... 

Ethyl 9a-hydroxy-11a,15a-bis(2-tetrahydropyranyloxy)-16,16-dimethyl-prosta-trans-2,trans-l3-dienoate Potassium hydroxide Manganese sulfate Acetic acid... 

Synthesis of 9-oxo-11 CH,1 Sol-bis-(2-tetrahydropyranytoxy)-16,16-dimethyl-prosta-trans-2, trans-13-dienoicacid 4gof ethyl 9a-hydroxy-1 la,1 5a-bis-(2-tetrahydropyranyloxy )-16,16-dimethyl-prosta-trans-2,trans-13-dienoate were dissolved In 130 ml of a mixture of ethanol-water (3 1), mixed with 3.9 g of potassium hydroxide and stirred at 25°C for 2 hours. The reaction mixture was acidified with aqueous solution of oxalic acid to pH 5, and diluted with 100 ml of water, extracted with ethyl acetate. The extracts were washed with water, dried over sodium sulfate and concentrated under reduced pressure to obtain 3,88 g of 90 -hydroxy-11a,15a-bis-(2-tetrahydropyranyloxy)-16,16-dimethyl-prosta-trans-2,trans-13-dienoic acid. 

Pyrrolo[l,2-a]azepin-5-one (11), prepared by cyclization of methyl 5-(pyrrol-2-yl)penta-2,4-dienoate (10) with sodium hydride in toluene, in trifluoroacetic acid solution forms the diatropic 5-hydroxypyrrolo[1,2-a]azepinium ion 12.216 6-Methyl-5//-pyrrolo[l,2-tf]azepin-5-one(mp41 -43 C), formed in low yield (20%) by the action of [(ethoxycarbonyl)methylene]triphenylphos-phorane on 4-(pyrrol-2-yl)but-3-en-2-one, behaves similarly. 

The next step in degradation involves hydrolysis of 2-hydroxy-6-keto-6-phenylhexa-2, 4-dienoate to benzoate and 2-hydroxy-penta-2,4-dienoate encoded by the hydrolase BphD. 

Both trifluoromethylbenzoates and trifluoromethylphenols prodnced 2-hydroxy-6-keto-7,7,7-trifluorohepta-2,4-dienoate, which is the immediate ring-fission prodnct. The triflnoromethyl group of the original substrates was retained in the terminal metabolites. 

Scheme 2.18 gives some representative olefination reactions of phosphonate anions. Entry 1 represents a typical preparative procedure. Entry 2 involves formation of a 2,4-dienoate ester using an a, 3-unsaturated aldehyde. Diethyl benzylphosphonate can be used in the Wadsworth-Emmons reaction, as illustrated by Entry 3. Entries 4 to 6 show other anion-stabilizing groups. Intramolecular reactions can be used to prepare cycloalkenes.264... 

Grieco utilized an aqueous intermolecular Diels-Alder reaction as the key step in forming the AB ring system of the potent cytotoxic sesquiterpene vernolepin. 87 Cycloaddition of sodium ( >3,5-hexa-dienoate with an a-substituted acrolein in water followed by direct reduction of the intermediate Diels-Alder adduct gave the desired product in 91% overall yield (Eq. 12.28). 

A Mitsunobu process simultaneously coupled the enyne acid fragment 4 to /J-lactam 10 and inverted the CIO stereochemistry to the required (S)-configured ester 11 in 93% yield. A deprotection provided alcohol 12, the key /J-lactam-based macrolactonization substrate, which, under conditions similar to those reported by Palomo for intermolecular alcoholysis of /J-lactams (Ojima et al, 1992, 1993 Palomo et al, 1995), provided the desired core macrocycle 13 of PatA 13 (Hesse, 1991 Manhas et al, 1988 Wasserman, 1987). Subsequent Lindlar hydrogenation gave the required E, Z-dienoate. A Stille reaction and final deprotection cleanly provided (-)-PatA that was identical in all respects to the natural product (Romo etal, 1998 Rzasaef al, 1998). This first total synthesis confirmed the relative and absolute configuration of the natural product and paved the way for synthesis of derivatives for probing the mode of action of this natural product. 

Methyl (5R)-2-methoxycarbonyl)-5,9-dlmethyldeca-2,8-dienoate Propanedioic acid, (3,7-dimethyl-6-oc enylidene)-, dimethyl ester, (R)- (12) (106431-76-9)... 

The annulation reaction of thioamides with 2-alkynoates and 2,3-dienoates under the catalysis of phosphine provides 4,5-dihydro-1,3-thiazoles, particularly those with 2-aryl substituents (Scheme 14).35... 

The above findings prompted us to study the reaction between a coordinated dienoate ligand and an external alkene. The... 

Thereafter, the reaction between the coordinated dienoate ligand in 106 and acrylonitrile was examined (Scheme 12). Surprisingly, this reaction is complete within 56 h (pseudo-first-order rate constant k — 1.4 x 10-5 s-1, ti/2 ca. 0.5 day) and affords only two products 107a and 107b in a ratio of 57 43 (or the correepsonding acids 103a,b via acid hydrolysis). Thus, in... 

Simple carbonylation and dimerization-carbonylation of butadiene take place in alcohol depending on the catalytic species of palladium. When PdCl2 is used as a catalyst with or without PPh3, 3-pentenoate (72) is the sole product (74, 75). On the other hand, when Pd(OAc)2 is used with PPh3, the dimerization-carbonylation takes place to give 3,8-nona-dienoate (73) (76, 77). 

A key reaction in the formal total synthesis of (-)-mycalamide A involved the intermolecular ruthenium-catalyzed Alder-ene reaction between 157 and 158 to give the dienoate 159 (Scheme 35).94 This regioselective reaction provided a 63% yield of 159, which was subsequently transformed to a key building block 160 which was taken on to (-)-mycalamide A. 

In the presence of a catalytic amount of phosphine, the reaction of ethyl 2,3-buta-dienoate with methyl acrylate took place at room temperature to afford a regioiso-meric mixture of the [3 + 2]-cycloadducts in good yield [191]. 

Lie and coworkers31 reported the synthesis and NMR properties of all geometrical isomers of conjugated linoleic acids. Pure geometric isomers of conjugated linoleic acid (CLA) were prepared from castor oil as the primary starting material. Methyl octadeca-9Z, 11 /i-dienoate (36) and methyl octadeca-9Z,llZ-dienoate (38) were obtained by zinc reduction of methyl santalbate (35, methyl octadec-11 -en-9-ynoatc) and methyl... 

In 1965, Danishefsky and Cunningham19 and Berchtold and coworkers20 simultaneously reported 1,6-addition reactions of enanimes to conjugated dienoates the zwitterionic intermediates cyclize spontaneously and eliminate an amine to furnish 1,3-cyclohexadienes... 

Nucleophilic 1,4- and 1,6-additions of cuprates and other organometallic reagents to acceptor-substituted dienes have been utilized extensively in target-oriented stereoselective synthesis52-61. Schollkopf and coworkers55 reported the diastereoselective 1,6-addition of a bislactim ether-derived cuprate to 3,5-heptadien-2-one (90% ds equation 17). The corresponding reactions of dienoates were conducted with the lithiated bislactim ether and proceeded with diastereoselectivities of >99% ds (equation 18)56 the adducts could be converted easily into diastereo- and enantiomerically pure amino acid derivatives. 

Alternatively, a chiral lithium amide was added regio- and diastereoselectively to an achiral 2,4-dienoate, and the 1,4-addition product formed could again be converted into the desired, stereochemically pure /J-lactam (equation 31)106. 

Isolated instances of 1,4-addition reactions of other hetero-nucleophiles to 4-en-2-ynoic acids and derivatives have been reported172-174. Thus, treatment of methyl 4-methyl-4-penten-2-ynoate with phenolate provided the 3-phenoxy-substituted conjugated dienoate (equation 71)172, and the 1,4-addition of water-soluble phosphines to 4-octen-2-ynoic acid afforded dienylphosphonium salts which were transformed into the corresponding phosphine oxides (equation 72)174. 

Only few examples have been reported so far on nucleophilic addition reactions to acceptor-substituted polyenes123,124,186 188. In 1933, Farmer and Martin186 examined the reaction of methyl 2,4,6-octatrienoate with sodium dimethyl malonate and isolated the 1,4-adduct as major product (equation 81). In contrast to this, 3,5,7-nonatrien-2-one and ethyl 2,4,6-octatrienoate react with organocuprates under 1,8-addition to provide the 4,6-dien-2-ones and 3,5-dienoates, respectively (equation 82)187. 

---