Revival of Thermal Aziridine–Alkene Cycloaddition: Pyrrolidine Synthesis in Terpenoid-Based Deep Eutectic Solvents

Abstract

A synthesis of pyrrolidines via atom-economic aziridine–alkene cycloaddition mediated by hydrophobic deep eutectic solvents (HDESs) is reported. HDESs, prepared from naturally occurring terpenoid compounds, serve as high-boiling reaction media and as alternatives to conventional petroleum-based solvents. This protocol proceeds in the presence of air without any special precautions, offering an approach to highly substituted pyrrolidine scaffolds. A broad range of N-aryl aziridines is used as azomethine ylide precursors, delivering pyrrolidines in up to 94% isolated yield. The methodology is further extended to a one-pot double cycloaddition directly from azide starting material, with solvent reusability and gram-scale synthesis also demonstrated.