1,2-Orthoacetate intermediates in silver trifluoromethanesulphonate promoted Koenigs–Knorr synthesis of disaccharide glycosides

Abstract

The three disaccharides lactose, cellobiose, and maltose in the form of their acetylated glycosyl bromides have been reacted with 8-ethoxycarbonyloctanol to provide the 1,2-trans-glycosides. Conventional Koenigs–Knorr and Helferich conditions provided these glycosides in poor yield but silver trifluoromethanesulphonate, N,N-tetramethylurea gave the disaccharide glycosides in 50–60% yield. Use of 2,4,6-trimethylpyridine as proton acceptor provided the corresponding 1,2-orthoacetates in 60–70% yield. These 1,2-orthoesters were rearranged by stannic tetrachloride to the 1,2-trans-glycosides. The isolation of acetylated 8-ethoxycarbonyloctanol from Lewis acid catalysed isomerisation of 1,2-orthoesters and from Koenigs–Knorr reactions in which N,N-tetramethylurea was the proton acceptor is discussed in terms of a reaction mechanism proceeding from glycosyl halide to glycosidic products via a 1,2-orthoester intermediate. This proposal is supported by 1 H nmr evidence for the presence of 1,2-orthoacetate in Koenigs–Knorr reaction mixtures, and by 1,2-orthoacetate isomerisation to glycoside by the conjugate acid of N,N-tetramethylurea.