ABSTRACT
The synthesis of oligosaccharides entered a new era of practicality in the mid-1970's with the introduction of silver triflate [l] as an activator of anomeric halides, and with the halide ion-catalyzed procedure [2]. The stereocontrolled synthesis of 1,2-trans-glycosides can be achieved by activation of the corresponding glycosyl halide bearing an acyl protecting group at the C-2 position in the presence of a heavy-metal salt (Koenigs-Knorr glycosidation) [3]. Neighboring group participation leads to an acyloxonium cation intermediate that reacts with an appropriate acceptor to give the 1,2-trans-glycoside directly, or through the intermediacy of an orthoester [4] (Scheme 1). When a nonparticipating benzyl group is present at C-2, the products are usually mixtures of 1,2-trans-and cis-glycosides. Employing Lemieux's halide ion-catalyzed procedure [2], the thermodynamically more stable 1,2-cis-glycosyl bromide is converted to the l,2-trans-anomer in situ by replacement with a bromide ion source. The 1,2-trans-bromide being more reactive than the 1,2-cis-isomer, is attacked by the nucleophile by an ion pair species, with inversion of anomeric configuration to generate a 1,2-cis-glycosidic linkage (see Scheme 1). However, the broad applications of
Scheme 1 I,2-trans-glycoside synthesis by Koenigs-Knorr-type glycosidations, and 1,2-cisglycosides by the halide ion catalyzed method.
