Mechanosynthesis of Enaminones and Mechanochemical Telescopic Synthesis of β,γ‐unsaturated Butyrolactams

Abstract

The stereoselective mechanochemical synthesis of Z‐enaminones and bis‐enaminones was achieved without any solid component in most cases, reacting 1,3‐dicarbonyl compounds with aliphatic/aromatic primary/secondary amines, which demonstrates the viability of reacting exclusively liquid reagents. The scale‐up was robust, from five to fifty and five hundred mmol without reduction in the reaction yield. The mechanochemical telescopic synthesis of β,γ‐unsaturated butyrolactams was achieved by formal [3+2] azaanulation reaction of intermediate enaminone with maleic anhydride, boosting the access of this potentially bioactive class of compound. The mechanochemical approach revealed its sustainable face in both syntheses, avoiding solid grinding auxiliary and purification by column chromatography. A symbol was suggested to differentiate the representation of the planetary ball mill from other mechanochemical reactors, wherein three spheres are surrounded by two curved arrows representing the two inherent movements of planetary trajectories of the reaction vessel of this equipment.