Synthesis of 2-trifluoromethylated quinolines from CF3-alkenes

Abstract

α-CF₃-enamines can be prepared by the reaction of pyrrolidine with the corresponding haloalkenes. The prepared enamines react with 2-nitrobenzaldehydes to give ortho-nitro-substituted α,β-diaryl-CF₃-enones highly stereoselectively in up to 88% yield. Subsequent reduction of the nitro-group by an Fe–AcOH system promotes intramolecular cyclization to afford 2-CF₃-3-arylquinolines in up to 99% isolated yield. High synthetic utility of all synthetic steps of the sequence was shown. A one-pot procedure was developed to give the target trifluoromethylated quinolines directly from enamines or haloalkenes.