| Abstract
| - Stereoselective synthesis of β-mannosides is one of the most challenging linkages to achieve incarbohydrate chemistry. Both the anomeric effect and the C2 axial substituent favor the formation of theaxial glycoside (α-product). Herein, we describe mechanistic studies on the β-selective glycosidation oftrimethylene oxide (TMO) using mannosyl iodides. Density functional calculations (at the B3LYP/6-31+G(d,p):LANL2DZ level) suggest that formation of both α- and β-mannosides involve loose SN2-like transition-state structures with significant oxacarbenium character, although the transition structurefor formation of the α-mannoside is significantly looser. α-Deuterium kinetic isotope effects (α-DKIEs)based upon these computed transition state geometries match reasonably well with the experimentallymeasured values: 1.16 ± 0.02 for the β-linkage (computed to be 1.15) and 1.19 ± 0.05, see table 2 forthe α-analogue (computed to be 1.26). Since it was unclear if β-selectivity resulted from a conformationalconstraint induced by the anomeric iodide, a 4,6-O-benzylidine acetal was used to lock the iodide intoa chairlike conformation. Both experiments and calculations on this analogue suggest that it does notmirror the behavior of mannosyl iodides lacking bridging acetal protecting groups.
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