Catalyst‐Free Regio‐ and Diastereoselective Synthesis of Heterocyclic Nucleosides in the Eco‐friendly Solvent 2‐Methyltetrahydrofuran^†

Abstract

Comprehensive Summary An efficient and practical synthesis of heterocyclic nucleosides is developed by a catalyst‐free highly regioselective and diastereoselective [3+2] annulation of α‐purine‐substituted acrylates with nitrones. The reaction operates with excellent functional group tolerance, very mild reaction conditions, and with the green, sustainable, and eco‐friendly 2‐methyltetrahydrofuran (2‐MeTHF) as solvent. Compared with other reactions of electron‐deficient olefin dipolarophiles with nitrones, different regioselective cycloaddition products were observed in this work. This 1,3‐dipolar cycloaddition reaction gives a series of isoxazolidinyl nucleosides in good to excellent yields with promising applications in biochemistry and medicinal chemistry.