3,8-Dienols synthesis

Penicillin V—see Penicillin, phenoxymethyl-, 7, 300 Penicilloate, benzyl-, 7, 303 Penicilloate, D-a-benzyl-a-methyl ester, 7, 303 Penillamine, benzyl-, 7, 303 Penillic acid, benzyl-, 7, 303 Penilloaldehyde, benzyl-, 7, 303 Penilloic acid, benzyl-, 7, 303 Penillonic acid, benzyl-methyl ester, 7, 303 1,2,3,4,6-Pentaazaindene nomenclature, 1, 18 Pentadeca-5,10-dienols synthesis, 1, 428 Pentadienol, tetrachloro-2H-pyran synthesis from, 3, 740 Pentadienonitrile, 5-(l,2-benzoselenazol-3-yl)-X-ray diffraction, 6, 334 Penta-2,4-dienonitrile, 5-(dimethylamino)-2-(2-thienyl)-... 

The asymmetric 1,4-addition of the dienolate of the optically active camphor derived 3-methyl-3-butenoate to 2-cyclopentenone gives a mixture of four diastereomers. The major adduct was applied in the synthesis of (—)-khusimone188. 

The different ratios of 52/53 produced by cycloadditions performed at atmospheric and high pressure, and the forma tion of the unusual trans adducts 53, have been explained by the facts that (i) Diels-Alder reactions under atmospheric pressure are thermodynamically controlled, and (ii) the anti-endo adducts 52 are converted into the short-lived syn-endo adducts 54 which tautomerize (via a dienol or its aluminum complexes) to 53. The formation of trans compounds 53 by induced post-cycloaddition isomerization makes the method more flexible and therefore more useful in organic synthesis. 

Scheme 1.8 shows some intramolecular enolate alkylations. The reactions in Section A involve alkylation of ketone enolates. Entry 1 is a case of a-alkylation of a conjugated dienolate. In this case, the a-alkylation is also favored by ring strain effects because y-alkylation would lead to a four-membered ring. The intramolecular alkylation in Entry 2 was used in the synthesis of the terpene seychellene. 

Another Japanese group developed the Baccatin III synthesis shown in Scheme 13.58. The eight-membered B-ring was closed early in the synthesis using a Lewis acid-induced Mukaiyama reaction (Step B-l), in which a trimethylsilyl dienol ether served as the nucleophile. 

TITANIUM-MEDIATED ADDITION OF SILYL DIENOL ETHERS TO ELECTROPHILIC GLYCINE A SHORT SYNTHESIS OF 4-KETOPIPECOLIC ACID HYDROCHLORIDE (Pipecolic acid, 4-oxo-, hydrochloride)... 

The reactivity of ethyl cyclopropylideneacetate (52b) has been exploited by Spitzner and Sawitzki in a new (formal) total synthesis of the diterpene ( + )-isoeremolactone 80 (Scheme 16) [25]. The key step of the synthesis is the addition of the enantiomerically pure dienolate 78 to the reactive acrylate 52b, to give a single isomer 79 in 92% yield. 

A simple two-step protocol for the generation of a terminal diene is to add allyl magnesium bromide to an aldehyde or a ketone and subsequent acid or base catalysed dehydration (equation 34)72. Cheng and coworkers used this sequence for the synthesis of some indole natural products (equation 35)72a. Regiospecific dienones can be prepared by 1,2-addition of vinyllithium to a,/l-unsaturated carbonyl compounds and oxidative rearrangement of the resulting dienols with pyridinium dichromate (equation 36)73. 

Treatment of 1-pyridinium sulphonate with sodium or potassium hydroxide generates sodium or potassium salts of 5-hydroxy-2,4-pentadienal (glutaconaldehyde), which are starting materials for a variety of transformations (equation 178)171b 301. For example, the reaction of the potassium salt with a carbon electrophile has been used for the preparation of a dienol aldehyde (equation 179)mb which was an intermediate in the total synthesis of a mutagen, (S)-3-(dodeca-l,3,5,7,9-pentaenyloxy)propane-l,2-diol. 

Considerable attention has been devoted to the preparation and chemistry of a,/3-unsaturated carbonyl compounds, which are valuable intermediates in organic synthesis [125]. Acid-promoted hydrolysis of alkoxyallenes has therefore frequently been employed to prepare a variety of functionalized a,/8-unsaturated carbonyl compounds [12b, 41, 44, 60, 126]. A recent example is illustrated in Scheme 8.54with C-l-silylated alkoxyallene 218 as a convenient starting material for the synthesis of bicyclo[5.4.0]undec-4-en-2-one 221. Sequential deprotonation and silylation at the terminal C=C bond efficiently transformed 218 into a 1,3-disilylated allene which was converted into the acryloylsilane 219 under acidic conditions. A [3 + 4] annula-tion of intermediate 219 with lithium dienolate 220 furnished bicydic compound 221 in good yield [127]. 

Since dienolates 1 and 2 represent diacetate synthons, the dienolate derived from 6-ethyl-2,2-dimethyldioxinone can be seen as a propionate-acetate syn-thon. The synthesis of the corresponding dienolate provides a mixture of the E and Z enolates in a 3 5 ratio. The reaction with Ti-BINOL complex 5 generates a 5 1 mixture with the syn isomer as the major diastereomer. After separation of the diastereomers, the enantiomeric excess of the syn isomer was determined to be 100%. The anti isomer was formed in 26% ee. The same transformation performed with boron Lewis acid 7 gave the anti isomer as the major compound, but only with 63% ee. The minor syn isomer was produced with 80% ee. The observed selectivity could be rationalized by an open transition state in which minimization of steric hindrance favors transition state C (Fig. 1). In all three... 

Terpenoid Synthesis from Isoprene.—Syntheses of the useful synthons (33) and (34) have been reported. The vinyl-oxygen bond of diketen is selectively cleaved by Me3SiCH2MgCl-NiCl2 to yield the synthon (35) which is readily converted into the dicopper dienolate (Vol. 7, p. 14) and prenylated to yield (36 X = C02H) after hydrolytic work-up and desilylation (36 X = C02H) yields... 

Another work of Duhamel and Ancel [59] related this synthesis of retinal via (3-ionylideneacetaldehyde. Condensation of methallyl-magnesium chloride with diethyl phenyl orthoformate (EtC CHOPh) led after bromination of the ene-acetal, deshydrohalogenation (NaOH 50%), ethanol elimination with hexamethyldisilazane (HMDS) and ISiMes, to the bromo-dienol ether. This latter was submitted to bromine lithium exchange and the lithio enol ether was then condensed with p ionylideneacetaldehyde to give retinal, Fig. (28). 

Pyrans lack aromatic properties and behave as dienolic ethers showing the instability predicted by MO calculations. Hence, the parent compound proved elusive and was not synthesized until 1962. Although several routes are available for the synthesis of this ring system, such is the variation in stability of 4//-pyrans no one method can be described as of widespread application. Routes to the 4//-pyran ring system have been reviewed <80H(14)337>. 

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