Koenigs-Knorr reaction orthoester formation

The synthesis93 of N-(2,4-dinitrophenyl)-3-0-(tetra-0-acetyl-/ -D-glu-copyranosyl)-L-threonine methyl ester (131) involved a two-step procedure. First, formation of the intermediate, L-threonine orthoester 130 was achieved by treatment of tetra-O-acetyl-a-D-glucopyranosyl bromide (128) with the methyl ester of N-(2,4-dinitrophenyl)-L-threonine94 (129) under the conditions of the Koenigs-Knorr reaction (see next paragraph), and this was then converted into the L-threonine glycoside 131. 

Helferich, Bohm and Winkler1 have reported that the use of iodine catalyzed the Koenigs-Knorr reaction, which was exceedingly slow when calcium chloride was used as an internal desiccant. This catalyst has since been used by a number of other workers.79 111-114 The work of Talley, Reynolds and Evans79 on the synthesis of the orthoester type of oligosaccharides, indicated that the presence of iodine favored the formation of a normal biosidic linkage, whereas the absence of iodine favored the formation of an orthoester linkage. 

The glycosidic hydroxyl undergoes preferential alkylation when the sugar is alkylated with one equivalent of dimethyl sulfate and alkali 49,4 0 ). The procedure is particularly valuable for obtaining methyl glycosides of the D-mannose type for which the Koenigs-Knorr reaction fails because of orthoester formation. Alkylation of tetra-0-acetyl-/3-D-fructopyranose with silver oxide and methyl iodide leads to the methyl /8-D-fructopyranoside tetraacetate 50). 

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