Anomeric halides

Anomeric halides follow the typical reactivity order F < Cl < Br < I for nucleophilic substitutions. They have been used in stereoselective O-glycosylation, nucleophilic displacement, and carbanion as well as in radical reactions. 

Glycoside Synthesis from Anomeric Halides TMSO OTMS TMSO-... 

The origins of this field are often traced to observations made by Paulsen5 in the 1970s with regard to the differences in rate at which anomeric halides are hydrolyzed. 

The next section describes briefly the procedures for the preparation of anomeric halides, trichloroacetimidates and thioglycosides and their modes of activation. 

If one can find ways to effect SN2 reactions of glycosyl halides with oxygen nucleophiles (e.g., sugar alcohols), selective access to both sets of anomeric halides could prove invaluable. Other studies which employ SN2 chemistry at glycosidic centers include the halide-assisted glycosylation developed by Lemieux et al.,45 the use of a participating solvent such as acetonitrile,46 and exploitation of torsional control of anomeric reactivity.47 This latter approach has been very successfully exploited by Crich and Sun in the synthesis of P-mannosides (Fig. 19).48... 

The direct metallation of sugar derivatives, shown in Figure 7.20, is a useful method for the preparation of anomeric nucleophiles. Anomeric halides and glycals are excellent substrates for this reaction. Additionally, selective generation of a and 3 anomers is possible. 

In contrast to C-glycosylation by nucleophilic adchtion to an electrophilic carbohydrate, the use of an anomeric anion has found limited use for such a reaction due to instability. However, C-glycosylation by means of anomeric anion species is of signihcance in some special cases [74], The anomeric anion intermediate can be stereoselectively prepared by (i) reduc-hve metalation of anomeric halides or sulfones, (ii) transmetalation of glycosyl stannanes, and (iii) direct deprotonation of the anomeric proton. This section deals with three types of the reaction using different anomeric anions. 

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