Stereodirecting Effects of 4‐O‐ortho‐cyanobenzyl Ether on Chemical Glycosylation with Glucopyranosyl Donor

Comprehensive Summary Here we report a systematic investigation on the stereodirecting effects of a 4‐ O ‐ ortho ‐cyanobenzyl ether ( o BCN) group with a glucopyranosyl donor. Experimental studies revealed that the glycosylation reactions using this donor generally show dual‐stereoselectivities depending on the acceptor nucleophilicity, that is, glycosylation of weak nucleophile acceptors generally affords α‐glycosides specifically while glycosylation of strong nucleophile acceptors affords β‐glycosides preferentially. DFT computations suggested that strong nucleophiles preferentially attack the predominant covalent α‐glycosyl triflate intermediate in an S N 2‐like manner, while weak nucleophiles preferentially attack the less stable and more reactive β‐glycosyl triflate with H‐bond mediated direction. The first and facile synthesis of a hexasaccharide repeating unit of serotype IV group B Streptococcus capsular polysaccharide demonstrated the versatile utility of glucosyl building blocks with an o BCN functionality in carbohydrate chemistry.