Skraup−Doebner−Von Miller Quinoline Synthesis Revisited: Reversal of the Regiochemistry for γ-Aryl-β,γ-unsaturated α-Ketoesters

A reversal of the standard regiochemistry of the Skraup−Doebner−Von Miller quinoline synthesis was observed when anilines were condensed with γ-aryl-β,γ-unsaturated α-ketoesters in refluxing TFA. The reaction is proposed to involve 1,2-addition of the anilines to γ-aryl-β,γ-unsaturated α-ketoesters to form Schiff's base adducts, followed by cyclization and oxidation. The products were unambiguously shown to the 2-carboxy-4-arylquinolines by spectroscopy and X-ray crystallographic analysis.