Hemiacetals Wittig reaction

The synthesis of 11-oxaprostaglandlns from o-glucose uses the typical reactions of gl cofuranose diacetonide outlined on p. 267. Reduction of the hemiacetal group is achieved a thioacetal. The carbon chains are introduced by Wittig reactions on the aldehyde grou] which are liberated by periodate oxidation and laaone reduction (S. Hanessian, 1979 G Lourens, 1975). 

The methyl enol ether 37 is oxidized to the a,/3-unsaturated aldehyde 39 via hemiacetal 38. Unsaturated aldehyde 39, elongated one carbon from the aldehyde 36, is prepared by the Wittig reaction of 36 to give 37, and application of this reaction[ 88]. 

The protection of the hemiacetal hydroxyl in Step B-2 was followed by a purification of the dominant stereoisomer. In Step C-l, the addition of the C(6) methyl group gave predominantly the undesired a-stereoisomer. The enolate was trapped as the trimethylsilyl ether and oxidized to the enone by Pd(OAc)2. The enone from sequence C was then subjected to a Wittig reaction. As in several of the other syntheses, the hydrogenation in Step D-2 was used to establish the configuration at C(4) and C(6). 

The hemiacetal exists as an equilibrium mixture of cyclic compound 20 and its open counterpart (21), but an aldehyde addition reaction can occur only with the acyclic form A Wittig reaction of the stabilized ylide leads to an a. (3-unsaluraied ester that has the configuration with respect to the double bond. This reaction occurs under neutral conditions, so 1,4-addition of the alcohol to the a.p-unsaturated ester is avoided.6 A subsequent DIBAH reduction leads to ally lie alcohol 6 in a reaction that ordinarily shows complete 1,2-selectivit. ... 

The stable hemiacetal tetrahydropyranol 94 was used in a Wittig reaction to give the unsaturated ester 95 mostly as the E-isomer. Oxidation, nitroaldol and elimination gave the unsaturated nitro-compound 98. It turns out that the aryl-lithium does conjugate addition without any copper and that it reacts exclusively with the nitroalkene to give 99. 

The stereochemistry of the alkene product in Wittig reactions is thought to be influenced by the reversibility of formation of the isomeric threo and erythro oxaphosphetanes (or betaines) which undergo stereospecific loss of triphenyl-phosphine oxide to give the trans (E) and cis (Z) alkenes, respectively (Scheme 4). Factors that enhance the reversibility of this initial step favour the threo intermediate and hence the (E) alkene. Stabilized phosphoranes give a predominance of the (E) alkene while non-stabilized phosphoranes give the (Z) alkene. In general, stabilized phosphoranes react readily with aldehydes (see Protocol 4) while non-stabilized phosphoranes will react with aldehydes, hemiacetals (see Protocol 5) and ketones.2,3... 

Use of the Wittig reaction on a reducing sugar is a handy method to generate a double bond, which can then be used as aradical acceptor. As shown in Scheme 8.18, D-galactose was classically transformed into a selectively protected hemiacetal 60 by benzyl alcohol glycosylation, protection of the primary hydroxyl, 3,4-acetonide formation and debenzylation. The Wittig reaction followed by desilylation afforded the triol 61, which was then selectively tosylated on the primary hydroxyl... 

This procedure was used in the synthesis of the upper chain of a prostaglandin 82 (see chapter 6) where the stereochemistry is related to the biological activity.13 Note that the aldehyde is tied up as a hemiacetal in the starting material 81 (see chemoselectivity chapter) and that the salt-free ylid is actually a carboxylate anion made with sodium derivative of DMSO in DMSO. As you will see in the next section, not all Wittig reactions are cis selective - those of stabilised ylids are trans selective. 

Synthesis from o-arabinose Two researcher groups" " have synthesized the intermediate 20 from D-arabinose (Scheme 4). The D-arabinose derivative 25 was benzoylated and hydrogenated to give the corresponding hemiacetal, which was then subjected to Wittig reaction to give 26 and 27. Reduction of 26 followed by debenzoylation led to the diol... 

Therefore, despite lower stereoselectivity (3 1) in the epoxidation step the benzyl ether 118 (Scheme 20) was converted into 123 and then converted into tetrahydrofu-ran 124. After Swem oxidation a mixture of the aldehydes is generated the isomer with the correct stereochemistry at C-2 cyclizes to the hemiacetal 125 whereas the second C-2 epimer did not cyclize and was thus easily removed by chromatography. By Wittig reaction 125 was transformed into 126 which was smoothly debenzylated under Hanesssian s conditions (15) to give alcohol 127. Inversion of configuration at C-2 was achieved by an oxidation reduction sequence with complete stereocontrol. 

Wittig reaction of hemiacetal 22 leads to co-hydroxy ester 23 prevalentiy as E isomer, which is oxidized by the Pfitzner-Moffatt method to aldehyde 24. Aldol... 

The reaction of 2,5-anhydro-3,4-0-isopropyIidene-DL-allose (450) (see Vol. 9, p. 22) with ethyl triphenylphosphoranylidene pyruvate at 90 °C gave the internal Michael-addition product (451) via the a)S-unsaturated ketoester formed in the Wittig reaction. Homo-C-nucleosides (452) containing 6-azauracil or 4-hydroxy-5-carboxamidopyrazole were elaborated from (451). Details of an earlier synthesis of the racemic hemiacetal (454), a precursor of carbocyclic C-nucleosides, have been published, together with an improved synthesis of (454) via the lactone (453) part of this route is outlined in Scheme 87. Condensation of the lactone... 

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