Open‐Close Strategy toward the Organocatalytic Generation of 2‐Deoxyribosyl Oxocarbenium Ions: Pyrrolidine‐Salt‐Catalyzed Synthesis of 2‐Deoxyribofuranosides

Abstract

The reaction of secondary amine salts with 2‐deoxy‐ribofuranoses under forcible conditions leads to the putative furanosyl oxocarbenium ion that is trapped with various alcohols to provide 2‐deoxy‐ribofuranosides. The observed anomeric selectivities range from an equimolar mixture to complete α‐selectivity in the case of bulky sugar acceptors. Owing to the mechanism and temperature of the transformation, the generated oxocarbenium ion shows little or no facial preference towards the nucleophilic attack of non‐carbohydrate acceptors and leads to a mixture of anomers in the case of benzyl and acetyl protected donors. However, the conformationally less flexible tetraisopropylsilyl protected donor reacted with both sugar and non‐sugar acceptors in a stereoselective fashion. Besides, the glycosylation with 2‐cyanoethanol gave the product with unexpected beta‐selectivity presumably due to nitrile effect. The operationally simple organocatalytic protocol provides easy access to otherwise difficult 2‐deoxy‐ribofuranosides/disaccharides.