Koenigs-Knorr method

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... 

From a historic perspective glycosyl chlorides and bromides introduced, respectively, by Michael [2] and Koenigs and Knorr [3] were the most widely used donors in the saccharide synthesis for a very long time. The introduction of 1,2-orthoesters in 1964 [4] was the first important attempt to find an alternative to the Koenigs-Knorr method. However, Paulsen in his 1990 review of reliable donors for glycosyl... 

The Koenigs-Knorr method in the presence of an insoluble silver salt proceeds mainly with inversion of configuration. Silver silicate and silver-silicate-aluminate have often been used as the heterogeneous catalyst. This procedure has been traditionally used for the synthesis of p-mannosidcs and has been recently reviewed.35 However, it only works well with very reactive halides and sufficiently reactive alcohol components. 

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,... 

R. R. Schmidt, New methods for the synthesis of glycosides and oligosaccharides. Are there alternatives to the Koenigs-Knorr method Angew. Chem. lnt. Ed. Engl. 25 212 (1986). 

Since 1965, a number of attempts for obtaining sialyl glycosides have been achieved [15,16], mainly by the classic Koenigs-Knorr method using Al-acetylneuraminyl halides 2 as glycosyl donors. However, the yield and stereoselectivity of the glycosides with sugar... 

II. General Methodology Employed 1. Koenigs-Knorr Method... 

The above, indirect, procedure for glycoside synthesis is the Koenigs-Knorr method. Glycosidation may be effected from monosaccharides directly by treatment with an alcohol in the presence of a mineral acid catalyst. For example, when a-D-galactose (13) is heated in methanolic solution containing 2 per cent of hydrogen chloride the thermodymanically more stable methyl a-D-galacto-pyranoside (14) (Expt 5.113) is formed preferentially, and may be isolated from the reaction product by crystallisation as the monohydrate. The less abundant /i-anomer may be recovered from the mother-liquors. 

New Methods for the Synthesis of Glycosides and Oligosaccharides — Are There Alternatives to the Koenigs-Knorr Method Schmidt, R. R. Angew. Chem lm Ed, Engi 1986, 25, 212. 

The existence of bile-acid glucosiduronates in urine and plasma of man under certain pathological conditions has now been recognized197,198 for identification purposes, several bile acid-3-yl /3-d-glucopyranosiduronic acids have been synthesized199 by the Koenigs-Knorr method. 

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