Influence of Configuration at the 4- and 6-Positions on the Conformation and Anomeric Reactivity and Selectivity of 7-Deoxyheptopyranosyl Donors: Discovery of a Highly Equatorially Selective l-glycero-d-gluco-Heptopyranosyl Donor.

Abstract

The preparation of four per-O-benzyl-d- or l-glycero-d-galacto and d- or l-glycero-d-gluco heptopyranosyl sulfoxides and the influence of their side-chain conformations on reactivity and stereoselectivity in glycosylation reactions are described. The side-chain conformation in these donors is determined by the relative configuration of its point of attachment to the pyranoside ring and the two flanking centers in agreement with a recent model. In the d- and l-glycero-d-galacto glycosyl donors, the d-glycero-d-galacto isomer with the more electron-withdrawing trans,gauche conformation of its side chain was the more equatorially selective isomer. In the d- and l-glycero-d-gluco glycosyl donors, the l-glycero-d-gluco isomer with the least disarming gauche,gauche side-chain conformation was the most equatorially selective donor. Variable temperature NMR studies, while supporting the formation of intermediate glycosyl triflates at -80 °C in all cases, were inconclusive owing to a change in the decomposition mechanism with the change in configuration. It is suggested that the equatorial selectivity of the l-glycero-d-gluco isomer arises from H-bonding between the glycosyl acceptor and O6 of the donor, which is poised to deliver the acceptor antiperiplanar to the glycosyl triflate, resulting in a high degree of SN2 character in the displacement reaction.