Side Chain Conformation and Its Influence on Glycosylation Selectivity in Hexo- and Higher Carbon Furanosides

We describe the synthesis and side chain conformational analysis of a series of four 6-deoxy-2,3,5-tri-O-benzyl hexofuranosyl donors with the d-gluco, l-ido, d-altro, and l-galacto configurations. The conformation of the exocyclic bond of these compounds depends on the relative configuration of the point of attachment of the side chain to the ring and of the two flanking centers and can be predicted on that basis analogously to the heptopyranose analogs. Variable-temperature nuclear magnetic resonance (VT NMR) spectroscopy of the activated donors reveals complex, configuration-dependent mixtures of intermediates that we interpret in terms of fused and bridged oxonium ions arising from participation by the various benzyl ethers. The increased importance of ether participation in the furanoside series compared to the pyranosides is discussed in terms of the reduced stabilization afforded to furanosyl oxocarbenium ions by covalent triflate formation. The stereoselectivities of the four donors are discussed on the basis of the benzyl ether participation model.