Electrochemically enabled C7 functionalization of quinolines from o-propynolanilines: divergent access to 4,7-dichloro and 4-chloro-7-alkyl (aryl) quinolines

Abstract

The regioselective functionalization of the C7 position of quinoline remains a formidable challenge due to its inherent electronic deactivation. Herein, we report an electrochemical strategy that enables the divergent synthesis of valuable C7-chlorinated and alkylated (arylated) quinolines from simple ortho-propynolaniline precursors. This method leverages electrooxidative dearomatization to generate key cyclohexadienimine intermediates, which undergo two distinct pathways dictated by the para-substituent: TMSCl-mediated cascade chlorination/cyclization delivers 4,7-dichloroquinolines, while substrates bearing para-alkyl/aryl groups (R² ≠ Me) undergo an aromatization-driven [1,2]-σ migration to furnish 4-chloro-7-alkyl/arylquinolines with high selectivity. This approach bypasses the reliance on pre-functionalized meta-chloroaniline substrates and hazardous chlorinating agents, operating under mild conditions. Gram-scale synthesis and further derivatizations highlight the practical utility of this method, offering a versatile and sustainable platform for constructing complex quinoline architectures.