Koenigs-Knorr reactions glucosidation

A substantial improvement in the synthesis of steroid /3-D-glucosid-uronic acid derivatives was achieved by Conrow and Bernstein,125 who introduced cadmium carbonate as a new and effective catalyst in the Koenigs-Knorr reaction procedure its use proved to be particularly convenient in the synthesis of such derivatives of phenolic steroids, where the yields obtained by using silver carbonate had not usually exceeded 10%. Thus, by employing cadmium carbonate, several succesful syntheses in the series of phenolic steroids have been claimed (see, for example, Ref. 126). 

Electrophilic catalysis of the departure of halogens in the century-old Koenigs-Knorr reaction is implicit in the use of heavy metal bases such as silver oxide and mercuric cyanide, but the first demonstration of electrophilic catalysis in water (in the hydrolysis of the p-glucoside of 8-hydroxyquinoline by first-row transition metals (Cu Np > C")) was by Clark and Hay in 1973. The observations were expanded to the more conveniently followed (because more labile) benzaldehyde methylacetals or tetrahydropyranyl derivatives of 8-hydroxyquinoline, whose hydrolysis is now known to give solvent-equilibrated oxocarbenium ions (Figure 3.19). Surprisingly, however, the observation of electrophilic catalysis of glycoside hydrolysis itself was not picked up by paper... 

Some of the most important syntheses of glycosides start from glycosyl halides, which are converted into acetylated glycosides, with Walden inversion, by reaction with alcohols or phenols in the presence of acid-binding compounds. For example, methyl tetra-0-acetyl-/ -D-glucoside is obtained from a-aceto-bromoglucose by this method (the Koenigs-Knorr reaction) 942... 

In conclusion, it is evident that the Koenigs-Knorr reaction gives low yields for the glucosidation of carotenoids that bear a secondary hydroxy group in a ring system. Further investigations of the partial synthesis of these compounds, by use of new, recently developed approaches, are imperative and will be useful also for structure elucidation. 

Koenigs-Knorr reactions have been used to prepare glycosides of natural products or otherwise of interest in biology as follows various cardiac glycosides (using Fetizon s reagentincluding 2,6-dideoxyhexopyranosides, a terpene D-glucoside, triterpene... 

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