Koenigs-Knorr glycosylation with glycosyl

As a representative example, Paulsen and Von Reessen used a sialyl bromide to apply the Koenigs-Knorr method to the synthesis of an a-2,3-linked disaccharide (Scheme 8) [7b]. Glycosylation of the galactose acceptor 19 with sialyl bromide 18 led to the desired disaccharide 20, although with poor stereoselectivity (ca. 1 1 a j8). The low yields of Koenigs-Knorr glycosylations with secondary alcohols are partly due to elimination of the sialyl halide and formation of the 2,3-dehydro derivative 21. 

The Koenigs-Knorr glycosylation method using glycosyl bromides or chlorides as donors dates back to 1901 (13), and it is still in wide use. The glycosylation reaction was originally achieved with silver carbonate as a promoter, but other heavy metal salts, especially silver triflate (21), have been introduced as more effective... 

Glycosylation at the C-26 hemiacetal of 38 was achieved by using the classical Koenigs-Knorr glycosylation. Treatment of 38 with rhamnosyl chloride 36 and silver tiiflate in the presence of TMU provided trisaccharide 39 in 55% yield. Hydroboration followed by PDC oxidation afforded desired ketone 4 0. A palladium (II) hydroxide catalyzed debenzylation of 40 under hydrogen atmosphere gave 2. This completes the first total synthesis of a saponin however, aqueous solutions of 2 were not sweet at all. ... 

The commercially available but expensive w-pentenol may be successfully recovered after this procedure by distillation and saved for subsequent applications. Koenigs-Knorr glycosylation of suitable glycosyl bromides with, for example, silver triflate (suitable for perbenzoylated glycosyl bromides [47]) or silver carbonate (for peracetylated bromides [55]) also provides access to NPGs (e.g. 

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... 

Other anomeric-oxygen exchange reactions have been recently investigated quite extensively. Closely related to the Koenigs-Knorr method is the introduction offluorine as the leaving group (Scheme 1, path B) (6,9-13). Because of the difference in halophilicity of this element as compared with bromine and chlorine, additional promoter systems besides silver salts were found useful as activators for glycosylation reactions (14-16). However,... 

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