The Koenigs-Knorr Reaction

This chapter focuses on Koenigs–Knorr reaction used for the synthesis of glycosides. The Koenigs–Knorr reaction is applicable to the preparation of both aryl and alkyl glycosides, and is widely used for the synthesis of glycosides having complex groups attached to the anomeric carbon atom—particularly oligosaccharides. The procedure involves the treatment of a per-O acylated glycosyl halide with an alcohol in the presence of a heavy-metal salt or an organic base as the acid acceptor; the latter enhances the rate of reaction and also prevents side reactions. It is noted that under the usual reaction-conditions the more-stable anomer is obtained, and the less stable anomer can be prepared only by a kinetically controlled reaction. Per-O-acylated glycosyl bromides react faster than the corresponding chlorides, and are therefore preferred for most reactions. Silver carbonate or silver oxide is commonly used as the acid acceptor in the Koenigs–Knorr reaction. Mercury (II) acetate instead of a silver salt has been also used.