Chromic acid oxidation in the synthesis of uronic acids. Use of the O-levulinoyl group to minimize acyl migration

Abstract

In the chromate oxidation of a partially acylated sugar derivative to form the corresponding uronic acid, acyl migration to the primary alcohol group is a frequent cause of interference. In contrast to more commonly employed ester substituents, the O-levulinoyl group is far less prone to migration during oxidations with Jones reagent (chromic-sulfuric acids). Examples described here include levulinoyl at O-5 of acylic and furanose derivatives, and both eq and ax O-4 of pyranose derivatives. It is also shown that, because of the acidity of the Jones reagent, use of the O-levulinoyl group, in combination with a primary p-anisyldiphenylmethyl substituent, permits sequential rapid hydrolysis of the latter and oxidation of the newly exposed alcohol group, which favors high overall yields. In contrast to its immobility in these oxidation reactions, when the levulinoyl group is on O-2 of an aldosyl bromide, it participates in 1,2-orthoester formation as rapidly as O-acetyl. The 2,3,4,6-tetraacetate of either anomer of methyl d-glucopyranoside is oxidized to a uronic acid in moderate yield, by chromic acid in 5:1 acetic acid-water.