Preparation of Thioglycosides

A great variety of methods for the preparation of alkyl and aryl 1-thioglycosides of aldoses have been described30-31  

From Acylated Aldoses by Reaction with a Thiol in the Presence of Lewis Acid30-39 

Fully acetylated hexopyranoses react with thiols in the presence of Lewis acids, such as BF3-Et20.32,33 The reaction is faster with 1,2-trans acetates than with the corresponding 1,2-cij ones and 1,2-trans products predominate. Alkyl, alkenyl, and aryl thioglycosides are produced by this method. Variations on this method include the use of trimethylsilyl34 or stannyl derivatives35 of the thiols. 

From Acylated Glycosyl Halides by Reaction with Thiolate Anion40-48 

In this classic41 and general method, an acylated glycosyl halide reacts with a thiolate anion to produce a 1-thioglycoside, usually with 1,2-trans configuration. With alkyl thiolates, re-acylation is normally required following this treatment. 

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The preparation of thioglycosides was thoroughly reviewed by Garegg.13 These versatile glycosides can be used directly in glycosylation reactions, or can be converted to a number of other glycosyl donors, including sulfoxides. 

However, two recent papers suggest that DMF is also a good solvent for this type of condensation under appropriate activation conditions of the donor. A simple and efficient method for the preparation of thioglycosides of N-acetyl-neuraminic acid has been developed [30]. This procedure involves the selective in situ S-deacetylation and activation of the 2-S-acetyl NeuSAc (24a) and the displacement of primary bromide of methyl glycosides (28a, 28b). The desired a(2->6) thioglycosides (29a,29b) were obtained in 75 and 82% yield. Condensation of the sodium salt (24b), freshly derived from (24 a) by selective S-deacetylation with sodium methoxide [16], with (28c) in DMF at 45 °C also gave the expected compound (29c) in 76% yield (Scheme 8) [31]. 

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... 

Partial hydrolysis of dithioacetals has been found useful for the preparation of anomers not obtained by the foregoing methods and also for preparation of fu-ranosidic 1-thioglycosides. 

Glycosylation of thioglycosides.1 1-Thioglycosides when activated with 1.5 equiv. of C,H,SeOTf, prepared in situ from QH SeCl and AgOTf, react at 0° to -40° with alcohols to form glycosides in 60-95% yield. The reaction is generally p-selective. 

A range of other sulfur(IV) and (VI) derivatives formally obtained by the oxidation of thioglycosides have been prepared, but they are apparently not employed to date in O-glycosylation reactions. These include glycosyl sulfenamides and sulfonamides, as well as sulfinates and sulfonates [289]. S-Glycosyl sulfenic acids have been prepared as transients by the syn-elimination of S-(2-cyanoethyl) glycosyl sulfoxides [311]. 

Yu, H. Ensley, H. E., An efficient method for the preparation of glycosides with a free C-2 hydroxyl group from thioglycosides. Tetrahedron Lett 2003,44, 9363-9366. 

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