In(OTf)3-catalyzed synthesis of 2-styryl quinolines: scope and limitations of metal Lewis acids for tandem Friedländer annulation–Knoevenagel condensation

Abstract

The catalytic potential of different metal Lewis acids has been assessed for the one-pot tandem Friedländer annulation and Knoevenagel condensation involving 2-aminobenzophenone, ethyl acetoacetate, and benzaldehyde to form 2-styryl quinoline under solvent free conditions. While various metal Lewis acids were effective in promoting the Friedländer annulation step, In(OTf)₃ was the only effective catalyst for the subsequent Knoevenagel condensation reaction suggesting In(OTf)₃ as the stand-alone catalyst for the tandem Friedländer–Knoevenagel reaction to form 2-styryl quinolines. The protocol is compatible with different variations of aromatic/hetero-aromatic aldehydes and α,β unsaturated aromatic aldehydes giving highly functionalized 2-aryl/heteroaryl vinyl quinolines. The catalyst can be recovered and reused to afford the desired product in very good to excellent yields.