Modular Construction of Functionalized 2-CF3-Indoles

Abstract

The reaction of α-CF3-β-(2-nitroaryl)enamines with benzaldehydes led to nitro-substituted α,β-diaryl-CF₃-enones in high yield. Subsequent reduction of the nitro-group to the amino moiety by the Pd/C-NH₄HCO₂ system resulted in intramolecular cyclization to form a 5-membered hemiaminal which is stabilized by the presence of a CF₃-group. The reaction of this hemiaminal with various nucleophiles afforded functionalized 2-CF₃-indoles isolated in up to quantitative yields. High efficiency and broad synthetic scope of all steps of the sequence were demonstrated. A possible mechanism of the reaction is discussed.