Mechanism of 3-O-Acyl-Directed α-Mannopyranosylation and Rationalization of the Contrasting Behavior of 3-O-Acyl Glucopyranosyl Donors

An investigation into the α-directing effect of 3-O-acyl groups in 4,6-O-benzylidene-directed mannopyranosylation is reported. No evidence was found by VT NMR experiments with ¹³C-enriched 3-O-benzoyl esters for the formation of a bridged ion. Inclusion of an axial 3-C-methyl group in the donors to destabilize the ester ground-state conformation and promote participation enabled the observation of a very minor bridged ion in the NMR experiments. In experiments conducted in the presence of diphenyl sulfoxide, the only species observed were the two mannosyl oxysulfonium ions, yet the reactions were still extremely α-selective. Overall, no support was found for participation by the ester at the 3-position as the main pathway for α-selectivity. An alternative hypothesis is advanced based on acceptor hydrogen bonding to the acyl group, which is oriented in its ground state toward the anomeric position and so is ideally placed to participate in such hydrogen bonding. The much weaker α-directing effect of a 3-O-acyl group in the glucopyranosyl series is explained by the steric clash with the equatorial substituent at C2, which interferes with the stereodirecting hydrogen bond, and by the ground-state conformation of the 3-O-acyl group that is less well-disposed for the acceptor–donor hydrogen bond.