Glycosyl fluorides, stability

Glycosyl fluorides are excellent precursors for glycosylations. Lewis acids promote the defluorination leaving a stabilized carbenium species which is able to react with nucleophiles, e.g. N-nucleophiles. The configuration at the newly formed C-N bond is not only influenced by the sugar configuration but also by the utilized Lewis acid. This means that this is not a clear SNl-type reaction SN2-type pathways also have to be considered.15 18... 

The stabilities are in the order fluoride > chloride > bromide > iodide. The fluorides are extremely stable, and may even be deacetylated without loss of fluorine, to give the corresponding glycosyl fluorides. The iodides, on the other hand, are unstable compounds which, even in favorable cases, decompose at room temperature within two weeks. The bromides show a reasonable balance between reactivity and instability, and have been by far the most widely used halides for synthetic work. Of recent years, the use of poly-O-feenzoylglycosyl bromides has become increasingly popular in studies in this group they are more stable than the acetates but more reactive than poly-O-acetylglycosyl chlorides. 

Potential leaving groups other than hydroxy can also be activated with acidic amine-HF complexes, if a sufficiently stabilized carbocation is formed as a reaction intermediate. Thus, glycosyl fluorides can be conveniently prepared from a variety of different glycosidic precursors, because of the stability of the intermediately formed glycosyl cation [134, 135] (Scheme 2.62). 

The assembly of the complex Le carbohydrates has also been reported by Nicolaou, using a strategy based on glycosyl fluorides as donors (Scheme 6.19) [60]. The approach underscores the chemical stability of thioglycosides, which were also employed to protect the anomeric centers (e.g., 109 and 110). The thioglycosides are smoothly converted into the active glycosyl fluor-... 

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