Remote 6‐ <i>O</i> ‐BCN Group Enables the Acceptor‑Gated α/β Glucosylation and Convergent Synthesis of a 4,6‐Branched α‐Hexaglucan

Here we report a systematic investigation of the stereodirecting effects of a remote 6-O-ortho-cyanobenzyl ether (BCN) group in glycosylation reactions with a glucosyl donor. These reactions exhibited dual stereoselectivity dependent on acceptor nucleophilicity: weak nucleophiles predominantly yielded α-glycosides, while strong nucleophiles produced β-glycosides. DFT computations revealed that the 6-O-BCN cyano group forms hydrogen bonds with both types of acceptors, mediating nucleophilic attack on covalent α- or β-glycosyl triflates through an S_N2-like mechanism. The acceptor-dependent stereochemical outcomes result from the combined effects of differentiated reactivity of the covalent triflate intermediates and the noncovalent hydrogen bonds. We demonstrated the utility of this stereoselective glycosylation method through the efficient synthesis of a 4,6-O-branched α-hexaglucan using glucosyl donors containing 2-O-, 4-O-, or 6-O-BCN functionality, showcasing its effectiveness for challenging iterative α-glucosylation reactions.