Neighboring-GroupParticipation by a Less Electron-Donating,Participating C‑2-Ester Ensures Higher 1,2-<i>trans</i> Stereoselectivity in Nucleophilic Substitution Reactions of FuranosylAcetals

Nucleophilic substitution reactions of C-2-acyloxy furanosyl acetals can be highly diastereoselective. We here show that the presence of a less electron-donating <i>p</i>-nitrobenzoyloxy group at C-2 of a furanosyl acetal can be of use to control the 1,2-<i>trans</i> stereoselectivity of acetal substitution reactions with higher stereoselectivity than the analogue with the more electron-donating benzoyloxy group, just as what was observed in the pyranosyl system. Computational results support a reaction manifold involving both open oxocarbenium ions and <i>cis</i>-dioxolenium ions to provide the 1,2-<i>cis</i> and 1,2-<i>trans</i> products. Participation by the less electron-donating C-2-(<i>p</i>-nitrobenzoyloxy) group forms a less stabilized <i>cis</i>-dioxolenium ion that reacts with the incoming nucleophile more readily to provide 1,2-<i>trans</i> products. The relative stability of the furanosyl <i>cis</i>-dioxolenium ion versus the open oxocarbenium ion is much higher than the pyranosyl system as a result of the lower energy penalty for forming the <i>cis</i>-fused [5,5]-bicyclic dioxolenium ion.