C-branched sugars

C-branched sugars or C-oligosaccharides are obtainable through indium-promoted Barbier-type allylations in aqueous media.151 Indium-mediated allylation of a-chlorocarbonyl compounds with various allyl bromides in aqueous media gave the corresponding homoallylic chlorohydrins, which could be transformed into the corresponding epoxides in the presence of a base (Eq. 8.62).152... 

L. Cottier, G. Remy, and G. Descotes, Photochemical synthesis of O-vinyl glycosides and their transformation into C-branched sugars, Synthesis p. 711 (1979). 

Non-anomeric positions can be regioselectively transformed by radical substitutions of halosugars or sulfur derivatives to yield mainly C-branched sugars by creation of new C-C bonds. 

Similar homolysis of xanthates derived from galacto compounds 33 by a tin radical can form deoxy sugars or, in the presence of acrylonitrile, C-branched sugars at C-3 such as 34 [37, 38] according to Scheme 17. 

All these syntheses of non-anomeric C-branched sugars show the influence of neighboring oxygenated groups as for the the preceding photosubstitutions at the anomeric positions. The importance of stereoelectronic effects seems predominant for all these radical reactions. 

The syntheses of these new C-branched sugars by regioselective and often stereoselective processes are obtained in better yields than with the precedingly mentioned glycals. The alkylation occurs at the less hindered side however, with methanol, some mixtures of isomeric C-branched sugars are obtained (Scheme 30). 

By photoaddition of other oxycarbinyl functionalized radicals, 1-4 ketols, 1-4 keto-ketals and 1-4 diketones are formed and a review of the main results has been published [59, 60]. Applications concerning the synthesis of natural C-branched sugars such as pillarose are given using this photoaddition methodology [61]. 

Similarly, the photolysis of unsaturated a-glycoside 76 leads to the vinylglycoside 77 in low yields. This on thermolysis undergoes a 3.3 sigmatropic rearrangement to yield the C-branched sugar 78 (Scheme 40) [74]. 

Allylindium, generated by transmetallation of 5-benzyloxy-4-methyl-2-pentenyl(tributyl)stannane, reacts with benzaldehyde leading to the l,5-< /z//-CE)-stereoisomer with a useful level of 1,5-stereoinduction (Equation (13)).151 2-C-branched sugars and C-disaccharides are prepared diastereoselectively by the indium-mediated reaction of 4-bromo-2-enpyranoside (Equation (14)).152... 

Canac, Y, Levoirier, E, Lubineau, A, New access to C-branched sugars and C-disaccharides under indium promoted Barbier-type allylations in aqueous media, J. Org. Chem., 66, 3206-3210, 2001. 

The aldol condensation, as the most extensively studied reaction in C-C bond formation, is also commonly applied to the synthesis of C-branched sugars. In general, it involves the base-catalyzed addition of one molecule of carbonyl compound to a second molecule in such a way that the a-carbon of the first attached to the carbonyl carbon of the second to form a /3-hydroxyl compound. 

Thiazole-based one carbon extension has been proved to be a useful tool in the synthesis of C-branched sugar derivatives [37]. To investigate an approach towards the synthesis of... 

C-branched sugar aceric acid [32] (O Scheme 21), 3-ulose 68 was treated with 2-(trimethylsi-lyl) thiazole (2-TST) in THF under thermodynamic control, followed by desilylation with tetra- -butylammonium fluoride (TBAF), led to a 5 1 mixture of endo- and exo-adducts 69 and 71, respectively. In contrast, addition of 2-thiazolyl lithium to compound 68 gave only the adduct 71, arising from sterically controlled exo-addition to the trioxabicylo[3.3.0]octane ring system in an unoptimized 40% yield. Benzylation of isomeric adducts 69 and 71 afforded 3-0-benzyl derivatives 70 and 72, respectively. The stereochemistry of thiazole addition to 3-ulose 68 was established by X-ray structural analyses of compounds 69 and 72, which revealed that 72 has the required C-3 conflguration for aceric acid synthesis. 

Starting from methyl 6-bromo-4,6-dideoxy-a-D-f/ reo-4-enopyranoside 103, 4-C-branched sugars have been prepared from various aldehydes with the same manner in a THF-phosphate buffer (0.11 M, pH 7.0) as the solvent (O Scheme 28). If the reaction is conducted in pure... 

Prandi [50] reported the preparation of methyl a-D-caryophylloside, a natural 4-C-branched sugar, in which the key step was diiodosamarium-promoted coupling reaction. As illustrated in O Scheme 30, C-C bond formation between the cmde acid chloride 106 and ketone 107 was mediated smoothly by Sml2 in tetrahydropyran (THP). Expected products were isolated in 63% yield and in a 8 Idiastereoisomeric ratio. Reduction of the major diastereomer 108 with sodium borohydride in methanol at 0 °C was very slow, but the expected 109 was eventually obtained in 73% yield after 24 h at room temperature. 

Over the past decades, radical chemistry has been developed into an important and integral part of organic chemistry. Radical cyclization becomes a facile and useful strategy for stereo-and regioselective C-C bond formation, affording useful chiral synthons for the synthesis of C-branched sugar derivatives [56,57]. The reactions in this section are divided into intramolecular and intermolecular free radical cyclization. 

In contrast to the erythro-compound 34 (OR = a-OEt), the reaction of the a-D-r/nw-enoside leads preferentially to alkylation at C-2 because of increased steric interaction between the nucleophile and the ra-located 6-acetoxymethyl group. All reactions proceed with clean inversion of configuration to furnish the C-branched sugars 39 and 4063. 

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