Glycosyl halide promoters

In the Koenigs-Knorr method and in the Helferich or Zemplen modifications thereof, a glycosyl halide (bromide or chloride iodides can be produced in situ by the addition of tetraalkylammonium iodide) is allowed to react with a hydrox-ylic compound in the presence of a heavy-metal promoter such as silver oxide, carbonate, perchlorate, or mercuric bromide and/or oxide,19-21 or by silver triflu-oromethanesulfonate22 (AgOTf). Related to this is the use of glycosyl fluoride donors,23 which normally are prepared from thioglycosides.24... 

Suitably protected glycosyl halides or acetates, upon Lewis-acid promoted SN1 heterolysis, generate glycosyl cation intermediates that can react with electron-rich arenes, heteroarenes, Me3SiCN, enoxysilanes, enamines, allyl silanes and stannanes, acetylenyl silanes and stannanes affording C-glycosyl compounds. 

The typical and widely used procedure for the activation of the anomeric centre involves the initial preparation of acylated glycosyl halides, which are then subjected to SN2-like displacement by a phosphate anion in the presence of a silver-containing promoter and a base. 

Despite its wide application in glycoside synthesis, the Koenigs-Knorr reaction suffers from several disadvantages (i) the glycosyl halides are unstable, (ii) excess toxic heavy metals are needed to activate the donor, and (iii) a desiccant (to absorb any liberated water) and an acid acceptor (to absorb the liberated hydrogen halide and can be a promoter itself) are often needed to increase the yield and suppress side reactions. 

It has been pointed out that the high reactivity of the poly-O-acyl-glycosyl halides is typical of the a-halogeno ethers. In this class of compound, the inductive polarization of the C—X bond is increased by an electromeric release of electrons from the oxygen atom and this promotes a unimolecular (rather than a bimolecular) reaction. Comparison of the rate of methanolysis of 2,3-dichlorotetrahydropyran (XXII) with those of 3,4,6-tri-0-acetyl-2-chloro-2-deoxy-a-D-glucosyl chloride (XXIII) and... 

In an extension of this method, Koenigs and Knorr subsequently reported that reaction between acylated glycosyl halides (bromides, chlorides, or iodides) with alcohols, in the presence of silver promoters (oxide or carbonate) furnished 1,2-trans alkyl glycosides. 

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