Wittig reaction with sugars

FIGURE 7.14 Example of Wittig reactions with sugars. 

Figure 2.8.1 Example of Wittig Reactions with Sugars ...

IV. Anomalous Wittig Reaction With Free and With Partially Protected Sugars. 284... 

Eliminations. An improved synthetic protocol based on a Wit-tig olefination strategy allows the preparation of carbon-linked pentasaccharides by a BuLi/HMPA-mediated generation of the ylide from a sugar phosphonium salt precursor and Wittig reaction with formyl mannopyranosides. ... 

The Wittig reaction, or its phosphonate modification, can be a very useful reaction in the synthesis of anomerically functionalized precursors to C-nucleosides, particularly when the ring-closure reaction leads to five-membered, anhydro derivatives, and occurs with a high degree of stereocontrol. Zhdanov and coworkers,130 showed that the following five-membered, Wittig products (179-182) were formed from various free sugars and (p-methoxybenzoyl)- and (acetyl-methylene)-triphenylphosphoranes. 

An interesting approach to carbobicyclic polyhydroxylated compounds was proposed by Jarosz.43 It was based on a Lewis acid transformation of sugar allyltins 82 into dieno-aldehydes 83 with the fi-geometry across the internal double bond exclusively. The Wittig-type reaction of 83 afforded a triene, which underwent cyclization under high pressure, providing derivatives of bicyclo[4.3.0]nonane 84. Alternatively, dienoaldehyde 83 was converted into the phosphonate 85, which afforded the bicyclo[4.4.0]-decene derivatives (86) upon reaction with an aldehyde and simultaneous cyclization of the resulting triene.43 (Fig. 29). 

The second synthesis of 654 and 655 makes use350,351 of the Wittig reaction. The (methylthio)methyl ether 656 is converted into the chloromethyl ether 657, which reacts with triphenylphosphine to yield a crystalline phosphonium salt (658). Reaction of 658 with phenyllithium gives a phosphorane, treatment of which with acryl-aldehyde leads to ethers 654 and 655 in —50% yield. Pure trtms-diene 654 was obtained352 in a reversed way consisting in preparation of a sugar ether acrylaldehyde (660) by replacement of the p-tolylsulfonyl group in 659, followed by reaction of 660 with methylenetriphenyl-phosphorane. 

A versatile protocol for the generation and cyclization of secondary radicals from hexo-pyranose sugars is shown in Scheme 3 [10], The Wittig reaction of reducing sugars with two eq of an alkylidene phosphorane readily provide hex-5-ene-l-ols, which were converted into hex-5-enyl radicals by the l-ff-imidazole-l-carbothioate. The cyclization reaction is carried out in refluxing benzene or toluene with tributyltin hydride and AIBN, according to... 

Chiral aldehydes such as N-protected a-aminoaldehydes and a-alkoxyalde-hydes as well as chiral butadienes derived from sugars by a Wittig reaction have also been used in the hetero Diels-Alder reactions successfully with the inducing stereogenic centers remaining in the obtained cycloadducts. 

Application of the Wittig reaction in the carbohydrate field is accompanied by certain difficulties. A correct choice of the initial sugar components is the main problem, owing to the basicity of phosphoranes and, especially, to the drastically basic conditions employed with phosphonium ylides (2a). It is not surprising, therefore, that protected (acetalated and aeetylated) aldehydo sugars and resonance-stabilized phosphoranes were used at first,3-5 although partially protected, and even unprotected, aldoses were shown to be amenable to the reaction with various resonance-stabilized phosphoranes, thanks to the presence of the carbonyl form in the mobile equilibrium. The latter reactions, however, are extremely complicated (see Section IV, p. 284). 

The basicity of the medium is considerably less when resonance-stabilized phosphoranes are employed, resulting generally in a normal course for the Wittig reaction. A direct correlation between the basicity of certain phosphoranes and their reactivity towards 2,4 3,5-di-0-benzylidene-aZde/n/do-D-ribose and 2,3,4,5,6-penta-O-acetyl-aldehydo-D-g ucose was not found,21 thus indicating a steric influence prevalent in the sugar components, in comparison with electronic factors in phosphoranes. 

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