Mechanochemical Aza-Vinylogous Povarov Reactions for the Synthesis of Highly Functionalized 1,2,3,4-Tetrahydroquinolines and 1,2,3,4-Tetrahydro-1,5-Naphthyridines

The aza-vinylogous Povarov reaction between aromatic amines, α-ketoaldehydes or α-formylesters and α,β-unsaturated dimethylhydrazones was carried out in a sequential three-component fashion under mechanochemical conditions. Following extensive optimization work, the performed on vibratory ball mill operating at 20 Hz using zirconium oxide balls milling jar, afforded 1,2,3,4-tetrahydroquinolines 1,2,3,4-tetrahydro- 1,5-naphthyridines functionalized C-2, C-4 also C-6, latter case. This protocol generally target compounds good to excellent yields diastereoselectivities. A comparison of representative examples with results obtained conventional conditions revealed that affords faster reactions comparable solvent-less environment.