Glycosyl halides stability

Glycosyl halide stability and reactivity 1.232.3 a -Selectivity in glycoside synthesis 1.23.2.4 Other variables in glycoside bond formation 1.2.3.23 Examples... 

Glycosyl halides, a very important group of carbohydrate derivatives, are commonly prepared14 from per-O-acylated sugars by reaction with hydrogen halides or halides of aluminum or titanium. The selection of the method depends mainly on the anomeric configuration of the substrate, the kind of its O-acyl groups, and the stability of the product to be prepared. 

Stabilized carbanions, such as malonyl ceubanions, which have a soft character, react with glycosyl halides affording the corresponding C-glycosyl malonates. Once more, the presence of a participating group at C-2 directs the attack of the nucleophile from the opposite side. An example of the application... 

Hi) Reduction of Glycosyl Halides with Radical Rearrangement. The reduction of acetylated or benzoylated halides or selenides with a low concentration of tributylstannane leads to 2-deoxy sugar derivatives (Scheme 11). The driving force of this radical reaction is the 1,2-cA-selective migration of an ester group because of the stabilization of the radical at C-2.46... 

In the case of organochromium(III) complex intermediates obtained from glycosyl halides, work by Somsak and coworkers showed that their decay into glycals [75] is marked by the remarkable stability of the organometalic compounds in aqueous solutions. From the same group came the radically new concept of using zinc metal under aprotic conditions [76]. In brief, they proposed that acetylated glycosyl bromides be treated with zinc dust in the presence of A-heterocyclic bases (e. g., 4-methylpyridine or 1-methylimidazole) in a variety of aprotic solvents (i. e., benzene, ethyl acetate, tetrahydrofuran, acetone, dichloromethane) to afford the... 

The reactivity of the glycosyl halides increases in reverse order compared with stability protective groups at different positions exert remote electronic effects . The influence of these groups does not depend only on the distance to the anomeric carbon atom thus electron-withdrawing O-protective groups at C-4 lower the C-1 reactivity quite strongly due to through-bond interactions. 

The above conclusions concerning the stability and reactivity of glycosyl halides and their dia-stereocontrol in substitution reactions with glycosyl acceptors have to be complemented by the other variables in glycoside bond formation. 

Due to the low thermal stability of many glycosyl halides reaction temperatures above room temperature are usually not applied. The general tendency to favor the stereoelectronically controlled SN2-type reaction is reason to use reaction temperatures as low as possible. However, solubility and reactivity are commonly the decisive factors for reaction temperature selection. 

The plication of these observations has also led to many excellent results in V-glycoside synthesis. (The discussion of the special aspects of N- and C-glycoside synthesis is beyond the scope of this chapter.) However, severe, partly inherent disadvantages of the Koenigs-Knorr method could not be overcome. These include the low thermal stability and the sensitivity to hydrolysis of many glycosyl halides, and the use of at least equimolar amounts of heavy metal salts as catalysts , which are partly toxic or even explosive, to mention only a few aspects. This had led to an increased search for improved methods applicable also to large scale preparations. 

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