Triflic acid-mediated N-heteroannulation of beta-anilino-beta-(methylthio)acrylonitriles: a facile synthesis of 4-amino-2-(methylthio)quinolines

Various functionalised 4-amino-2-(methylthio)quinolines are synthesised through triflic acid-mediated N-heteroannulation of alpha-functionalized-beta-anilino-beta-(methylthio)acrylonitriles for the first time. The N-heteroannulation process is highly chemoselective and has mild reaction conditions. However, this process fails in the absence of the beta-methylthio group in the acrylonitriles. In addition, a new double N-heteroannulation process is demonstrated to synthesise indolo[3,2-c]quinolines from non-heterocyclic precursors. Natural product isocryptolepine is synthesised in four steps from an acyclic precursor.

Automated summary

Functionalised 4-amino-2-(methylthio)quinolines were successfully synthesised through triflic acid-mediated N-heteroannulation, demonstrating high chemoselectivity and mild reaction conditions. Additionally, a new double N-heteroannulation process was developed for the synthesis of complex indolo[3,2-c]quinolines from non-heterocyclic precursors. Natural product isocryptolepine was efficiently synthesised in four steps from an acyclic precursor.