Further studies on cation clock reactions in glycosylation: observation of a configuration specific intramolecular sulfenyl transfer and isolation and characterization of a tricyclic acetal

The use of the 2-O-(2-trimethylsilylmethallyl) group as intramolecular nucleophile and cation clock reaction in the glucopyranose series depends on the nature of the glycosyl donor. As previously reported, with trichloroacetimidates the anticipated intramolecular Sakurai reaction proceeds efficiently and is an effective clock, whereas with sulfoxides complications arise. The source of these complications is now shown to be an intramolecular sulfenyl transfer reaction between the tethered allylsilane and the activated sulfoxide. These results illustrate how a different unimolecular clock reaction may be required for a given cation when it is generated from different donors in order to avoid side reactions. The synthesis and cyclization of a 2-O-(3-hydroxypropyl) glucopyranosyl sulfoxide leading on activation to the formation of a trans-fused acetal is also described. The formation of this crystallographically-established transfused acetal is discussed in terms of the high effective concentration of the intramolecular nucleophile which leads to a high degree of a S(N)2 character in the displacement of the a-glucosyl triflate or at the level of the corresponding alpha-CIP. The possible use of such intramolecular alcohols as clock reactions and their limitations is discussed. (C) 2016 Elsevier Ltd. All rights reserved.