Koenigs-Knorr method catalysts

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. 

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. 

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. 

To overcome difficulty (i), a leaving group X of the glycosyl donor has been extensively studied for more than 100 years, which is a continued central issue in the area of carbohydrate chemistry. The activation of the Cl carbon is achieved by combination of X with a catalyst. The following glycosylations are well known they are, chronologically, (1) the Koenigs-Knorr method (1901)... 

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