Catalyst-free Regio- and Diastereoselective Synthesis of Heterocyclic Nucleosides in the Eco-friendly Solvent 2-Methyltetrahydrofuran

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.