Does neighboring group participation by non-vicinal esters play a role in glycosylation reactions? Effective probes for the detection of bridging intermediates.

Abstract

Neighboring group participation in glycopyranosylation reactions is probed for esters at the 3-O-axial and -equatorial, 4-O-axial and -equatorial, and 6-O-sites of a range of donors through the use tert-butoxycarbonyl esters. The anticipated intermediate cyclic dioxanyl cation is interrupted for the axial 3-O-derivative, leading to the formation of a 1,3-O-cyclic carbonate ester, with loss of a tert-butyl cation, providing convincing evidence of participation by esters at that position. However, no evidence was found for such a fragmentation of carbonate esters at the 3-O-equatorial, 4-O-axial and -equatorial, and 6-O positions, indicating that neighboring group participation from those sites does not occur under typical glycosylation conditions. Further probes employing a 4-O-(2-carboxy)benzoate ester and a 4-O-(4-methoxybenzoate) ester, the latter in conjunction with an (18)O quench designed to detect bridging intermediates, also failed to provide evidence for participation by 4-O-esters in galactopyranosylation.