Koenigs-Knorr method glycoside synthesis

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. 

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). 

Scheme 1 1,2-tranj-glycoside synthesis by Koenigs-Knorr-type glycosidations, and 1,2-cis-glycosides by the halide ion catalyzed method. 

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 plication of these observations has also led to many excellent results in V-glycoside synthesis. (The discussion of the special aspects of N- and C-glycoside synthesis is beyond the scope of this chapter.) However, severe, partly inherent disadvantages of the Koenigs-Knorr method could not be overcome. These include the low thermal stability and the sensitivity to hydrolysis of many glycosyl halides, and the use of at least equimolar amounts of heavy metal salts as catalysts , which are partly toxic or even explosive, to mention only a few aspects. This had led to an increased search for improved methods applicable also to large scale preparations. 

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