Reactions of Carbohydrate Triflates

Increasing die effective nucleophilicity of an ion allows S 2 substitution reactions to occur under milder conditions. An anion will become a better nucleophile when it is less effectively solvated and when it is further separated from its counterion. Methods that can achieve these changes include selection of a tetraafldammomum counterion [see Eqs. (6) and (6)], addition of a crown ether or a cryptand [see Eq. (7)], and use of a solvent that effectively solvates cations [see Eqs. (1) and (2)]. 

The nucleophile for which increased reactivity is most critical is the fluoride ion [3,4], Water molecules bind tightly to this ion, and their presence dramatically reduces its effective nucleophilicity. A variety of fluoride ion sources have been used in an effort to improve product yields in deoxyfluoro sugar synthesis [26,34]. The yields of substitution and elimination products generated from reactions with fluoride ion from several sources are listed in Table 2 [26]. Currently, the most attractive source of fluoride ion is tris(dimethylanuno)-5ulfur (trimetbylsilyl)difluoride (TASF), which is soluble in a variety of oiganic solvents and produces an anhydrous fluoride ion [33]. 

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A review of the synthesis and reactions of carbohydrate-triflates included a comprehensive compilation of all reported triflates. 

The danger of formation of sugar pyridinium salts when using tri-fluoroacetic anhydride in pyridine may be avoided by using 2,6-di-t-butyl-4-methylpyridine. Reaction of carbohydrate triflates with cyanide ion allows inversion at the hydroxy carrying centre either sodium cyanide or tetra-n-butylammonium cyanide were used in a one-... 

Aqueous aza-Diels-Alder reactions of chiral aldehydes, prepared from carbohydrates and with benzylamine hydrochloride and cyclopentadiene, were promoted by lanthanide triflates (Eq. 12.65).137 The nitrogen-containing heterocyclic products were further transformed into aza sugars, which are potential inhibitors against glycoprocessing enzymes. 

Acetal handle 78 synthesized from Merrifield resin and 4-hydroxy-benzaldehyde was applied to the solid-phase synthesis of carbohydrates and 1-oxacephams (Scheme 41) [90]. For the latter, a 1,3-diol was initially anchored to the support to form a cyclic acetal. A ring opening reaction with DIBAL generated a resin-bound alcohol which was converted to the corresponding triflate for A-alkylation with 4-vinyl-oxyazetidin-2-one. A Lewis acid catalyzed ring closure released 1-oxa-cephams from the support. 

R. W. Binkley and M. G. Ambrose, Synthesis and reactions of caibohydrate trifiuoromethane-sulfonates (carbohydrate triflates), J. Carbohydr. Chem 3 1 (1984). 

Until the introduction of triflate or imidazylate esters in carbohydrates, SN2-displacements of carbohydrate sulfonates with charged nucleophiles in certain positions of hexopyranose orfuranose derivatives were not possible, or gave low yields of substituted products owing to the predominance of elimination or rearrangement reactions [6,22,32,33]. 

Douglas, S P, Whitfield, D M, Krepinsky, J J, Silver trifluoromethanesulfonate(triflate) activation of trichloroacetimidates in glycosylation reactions, J. Carbohydr. Chem., 12, 131-136, 1993. 

Rencurosi A, Lay L, Russo G, Caneva E, Poletti L (2006) NMR evidence for the participation of triflated ionic liquids in glycosylation reaction mechanisms. Carbohydr Res 341 903-908... 

Differential reactivity of carbohydrate hydroxyls in glycosylation reactions under silver triflate promotion... 

Carbohydrates. - The phosphonic acid (193), an analogue of the bacterial cell wall component 3-deoxy-D-manno-2-octulosonic acid, has been synthesised by the reaction of 2,3 5,6-di-0-isopropylidene-D-mannitol triflate with the formylphosphonate anion equivalent (192) followed by deprotection. Compound (193) slowly decomposed to give the corresponding lactone and... 

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