Conformational Locking Enables Chemoselective Direct 2-Deoxyglycosylation of C-4 Equatorial Glycals under Bi-Catalysis.

We demonstrate the chemoselective 2-deoxyglycosylation of formidable C-4 equatorial glycals enabled by a conformationally constrained protecting-group strategy. A proof-of-principle for the Bi(OTf)3-mediated 2-deoxyglycosylation of trans-fused 3,4-O-TIPDS-protected l-rhamnal, d-glucal, and d-xylal is illustrated using carbohydrates, amino-acids, and bioactive-natural products, providing structurally diverse 2-deoxy and 2,6-dideoxyglycoconjugates. Mechanistic insights into the distinctive structures of the glycosyl species revealed that conformational locking restricts the accessible 5H4 glycal and 4H3 oxocarbenium ion conformations, thereby favoring 1,2-addition and circumventing the Ferrier pathway.