Unlocking the New Reactivity Pattern of Aza-1,6-Enyne: Iodine Catalyzed, Chemo-and Stereoselective Synthesis of Oxazolidinones

Abstract

Chemo-and stereoselective cyclization of aza-1,6-enyne is reported, demonstrating an unconventional and metal-free approach to synthesize the oxazolidinone core. The reaction proceeds efficiently in the absence of metal, additive, and solvent, utilizing molecular iodine as a catalyst under neat conditions at room temperature. The reaction selectively engages the carbonyl group (of enone) while leaving the alkene part of enone intact, which provides an alkene handle for further functionalization. This novel cyclization process represents a significant advancement in green chemistry as it eliminates the need of expensive reagents and solvents. The broad substrate scope and simple reaction conditions make this a sustainable, attractive, simple, and practical synthetic strategy. Moreover, the methodology enables the successful incorporation of a deuterated methoxy group when CD3OD is employed. Green-metric analysis revealed the sustainability of the protocol, delivering oxazolidinones with high atom economy (77.59%), complete carbon utilization, favorable reaction mass efficiency (77.6%), and a low E-factor (0.62), highlighting its environmentally benign nature.