Synthesis of functionalized quinolines from the cascade reactions of N-aryl amidines with two CF3-ynones via C–H/N–H/C–N/C–C bond cleavage

Abstract

Presented herein is a novel synthesis of CF₃- and alkynyl-substituted quinoline derivatives based on Rh(III)-catalyzed cascade reactions of N-aryl amidines with two CF₃-ynones. The formation of products involves a cascade process including aryl alkenylation followed by alkenyl alkynylation and intramolecular condensation via C–H/N–H/C–N/C–C bond cleavage. In this cascade procedure, the CF₃-ynone plays multiple roles by acting not only as an alkenylating reagent but also as an alkynylating reagent and a source of the CF₃ group. To our knowledge, such a reaction pattern has not been previously disclosed. In general, this newly developed protocol features easily accessible substrates, good compatibility with various functional groups, mild conditions with air as a sustainable oxidant and a unique reaction pathway. Furthermore, the products could be conveniently transformed into polycyclic CF₃-benzo[k]phenanthridines through an easy-to-run intramolecular annulation reaction. In addition, studies on the cytotoxicity of selected products against several human cancer cell lines demonstrated their potential as lead compounds for the development of novel anticancer drugs.