Neighboring-Group Participation by a Less Electron-Donating, Participating C-2-Ester Ensures Higher 1,2-trans Stereoselectivity in Nucleophilic Substitution Reactions of Furanosyl Acetals

Nucleophilic substitution reactions of C-2-acyloxy furanosyl acetals can be highly diastereoselective. We here show that the presence of a less electron-donating p-nitrobenzoyloxy group at C-2 of a furanosyl acetal can be of use to control the 1,2-trans 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 cis-dioxolenium ions to provide the 1,2-cis and 1,2-trans products. Participation by the less electron-donating C-2-(p-nitrobenzoyloxy) group forms a less stabilized cis-dioxolenium ion that reacts with the incoming nucleophile more readily to provide 1,2-trans products. The relative stability of the furanosyl cis-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 cis-fused [5,5]-bicyclic dioxolenium ion.