Sugar phosphoranes

Zhdanov and Polenov have reported58 a synthesis of the first sugar phosphorane (70), which was shown to react with p-nitro-and o-hy-droxy-benzaldehyde, forming unsaturated ketoses 71 and 72, respectively. Attempted reactions with p-dimethylamino-, p-hydroxy-, and 2,4-dihydroxy-benzaldehyde were unsuccessful. The formation of the dienic ketose 72 is undoubtedly caused by /3-elimination of a methoxyl group during treatment of the reaction mixture with aqueous sodium hydroxide during isolation. 

Sugars having a difluoromethylene group were prepared by reaction of an aldehyde group in sugars with difluoromethylene tris(dimethyl-amino)phosphorane some of these were 554- 559. Similarly, (Z)- 560) and f ))-. tw-bromofluoroalkene 561 were prepared from l,2 3,4-di-0-iso-propylidene-a-D-gfl/ac/o-hexodialdo-l,5-pyranose (395) by treatment with Ph3P=CFBr. 

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... 

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. 

Besides such utilization, certain studies9(e),(d),17,21,24,29(c) have been dedicated to a systematic examination of the reactivity of sugar derivatives and phosphoranes at qualitative and even semi-quantitative21 levels. 

Ketones are known to be usually unreactive towards resonance-stabilized phosphoranes, excluding ethoxycarbonylmethylenetriphe-nylphosphorane.z(f) L-Sorbose pentaacetate was, however, reported51 to react, although incompletely, with acetylmethylenetriphenyl-phosphorane and certain aroylmethylenetriphenylphosphoranes, giving branched-chain, olefinic sugars (69) in about 25% yield. 

It has been shown in the preceding Sections that the reactivity of various carbonyl-containing phosphoranes provides a direct avenue to introduction of the carbonyl function in a sugar molecule. There is, however, an alternative mode of such transformation that consists in introduction of such carbonyl precursors as enol, thioenol, or enamino groupings, provided that appropriate ylides (149) are available and that the final products may be converted into carbonyl compounds under mild conditions. 

The introduction of the phosphonate grouping into a sugar molecule (see Section III, 3 p. 260) has been further investigated by Paulsen and coworkers.97 Thus, the phosphonate phosphorane 120a was shown to react with 2,3,4,5,6-penta-O-acetyl-a/dehydo-D-glucose, 2,3 4,5-di-0- isopropylidene - aldehydo - D - arabinose, and 2,4-0-ethylidene-a/dehi/do-D-erythrose, leading to the unsaturated phos-phonates 229, 230a, and 231, respectively, in moderate yields. 

Wittig reactions of a-alkoxy aldehydes and sugar lactols, such as pentose ketal (48), with stabilised ylides usually proceed with low ( )-selectivity. However, Harcken and Martin have discovered that treatment of these aldehydes with (methoxycarbonylmethylene)tributyl phosphorane (49) and a catalytic quantity of benzoic acid produces the heptenonate (50) with a E Z ratio of 95 5. The stereoselectivity of the reactions between aldehydes and spirophosphoranes (51) has been examined and the phosphoranes found to favour the formation of (Z)-a,p-unsaturated aldehydes and amides. ... 

Numerous examples of this synthetic sequence, not limited to stabilized phosphoranes, can be found in the literature. The method is supposed to be applicable to all secondary hydroxyl groups of sugar rings. Chain extension at the primary hydroxyl group or at the hemiacetalic carbon using Wittig olefination will be examined later on in this chapter (Section 11.4). 

The reverse strategy, which consists of using a carbohydrate derived phosphorane, is seldom used because some elimination problems arise during the generation of sugar-derived phosphoranes. One of the first syntheses of such compounds was reported by Secrist [179]. 

Jarosz, S, Mach, M, Phosphonate versus phosphorane method in the synthesis of higher carbon sugars. Preparation of D-erythro-L-manno-D-gluco-dodecitol, J. Chem. Soc., Perkin. Trans. 1, 3943-3948, 1998. 

Jarosz, S, Salanski, P, Mach, M, Application of stabilized sugar-derived phosphoranes in the synthesis of higher carbon monosaccharides. First synthesis of a C-21-dialdose, Tetrahedron, 54, 2583-2594, 1998. 

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