Theoretical study on the effects of a 4,6-O-diacetal protecting group on the stability of ion pairs from D-mannopyranosyl and D-glucopyranosyl triflates.

ABSTRACT

Ion pair formation from 2,3-di-O-methyl-4,6-O-formylidene-α-D-mannopyranosyl triflate αTMan and its D-glucopyranosyl counterpart αTGlc was investigated at the DFT(M06-2X) level of theory, for the purpose of clarifying the effects of the 4,6-tethering on the structure and stability of α- and ß-contact ion pairs and solvent-separated ion pairs at -78 °C. In both mannopyranosyl and glucopyranosyl triflates, the 4,6-O-formylidene group destabilized (4)H3-type conformers of the α-contact ion pairs, rendering B2,5-types the exclusive conformers for this species. The B2,5-like α-contact ion pair from αTMan was 3.5 kcal/mol more stable than that from αTGlc, probably due to the stabilizing effect by the planar O-5-C-1-C-2-O-2 dihedral angle of the former. This difference in stability of the α-contact ion pair between the mannopyranosyl and glucopyranosyl series gives insights into the mechanisms underlying the reported experimental observation that highly ß-selective mannosylation can be achieved with 4,6-O-diacetal mannopyranosyl donors.