Metal-free regioselective construction of 2-aryl-substituted quinolines via Aza-Henry (Nitro-Mannich) reactions under neat conditions

Abstract

A new and practical synthetic approach to construct 2-aryl-quinoline derivatives has been described through the sequential Aza-Henry (Nitro-Mannich) reaction using readily available 2,3-dihydro-1H-inden-5-amines, aldehydes and nitroalkanes under one-pot solvent-free reaction conditions using TsOH·H₂O as the sustainable catalyst. In this regioselective approach, we described a cascade that proceeds through a sequential imine formation/Aza-Henry reaction/cyclization/denitration/rearrangement followed by oxidative aromatization to afford diverse 2-aryl-quinolines. This approach features large substrate scope, good functional group tolerance, mild reaction conditions and excellent yields with gram scale synthetic utility.

Graphical Abstract

Keywords:

• 2-Aryl-quinolines
• Aza-Henry (Nitro-Mannich) reaction
• metal-free approach
• excellent yields
• scalable method