Scheme 9

Scheme 11

moted by PST at -70°C in a 2:1 ratio of CH3CN to CH2Cl2, isolated yields of 6080% and stereoselectivities of 19:1 a:5 were observed. A representative example is shown in Scheme 12. Interestingly, when the reaction was conducted under high dilution (0.01 M in donor) the stereoselectivity improved to better than 99:1 a:5, albeit at the expense of overall yield (52%).

Regarding the reaction mechanism, Whitesides and coworkers also postulated that the presence of a ¡-nitrilium ion was the source of stereocontrol. In their proposed mechanism, the xanthate 27 initially reacts with the PST promoter to form 35 (Scheme 13). Subsequent loss of 36 leads to the oxocarbenim intermediate 31. Attack by acetonitrile is presumed to occur from the less hindered a face and leads to the presumably thermodynamically more favorable equatorial nitrilium ion 37 because of the reverse anomeric effect [13,14]. However the equatorial nitrilium ion is believed to be in equilibrium with the more reactive 5 species 32. Acetonitrile is then displaced from this species by the glycosyl acceptor in an SN2-like manner for form the a-glycosidic linkage in compound 38

The aforementioned experimental data do support this mechanism to some extent. First of all, the stereoselectivity is independent of the anomeric configuration of the starting material. A 1:1 mixture of xanthate anomers reacts to give predominantly the a-glycoside in acetonitrile, and the reaction by-product 36 was isolated and fully characterized. These data suggest that the xanthate is activated by the thiophilic promoter and glycosylation does not proceed through an SN2-type mechanism. Finally, Whitesides proposes that the gain in stereoselectivity that was observed by performing the reaction dilute in acetonitrile corresponds to an increase in the [MeCN]/[acceptor] ratio. The authors believe that a competition exists between acetonitrile and the acceptor alcohol for the oxocarbenium ion intermediate. When the concentration of the glycosyl acceptor is high enough, the alcohol reacts directly with oxocarbenium ion 32 to form the ¡-glycoside. However, an increase in the amount of acetonitrile favors nitrilium ion formation over direct glycosylation, and since nitrilium ion formation is the stereocontrolling element, higher a:5 ratios are observed.

Takahashi and coworkers examined a novel approach to stereoselective sialy-lations by incorporating an auxiliary into the ester [15]. An electron-donating group with an appropriate linker to the carboxylate carbon was anticipated to stabilize an oxocarbenium ion through long-range participation. Activation of compound 39, where X is an electron-donating group, would produce oxocarbenium ion 40. This intermediate could be stabilized by X to provide an equilibrating mixture of 5 and l y o o

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