Synthesis of highly substituted 2-perfluoroalkyl quinolines by electrophilic iodocyclization of perfluoroalkyl propargyl imines/amines

Abstract

A series of highly substituted 2-perfluoroalkyl-3-iodoquinolines are prepared by two different methods in good to excellent yields under mild reaction conditions. The first method involves iodocyclization of perfluoroalkyl propargyl imines with I₂-CAN. The second method involves iodocyclization of perfluoroalkyl propargyl amines using I₂ and ICl. The perfluoroalkyl propargyl amines are prepared in excellent yields viaSonogashira coupling of easily accessible imidoyl iodides with alkynes followed by reduction with NaBH₃CN. The scope of this methodology is extended by using the resulting 2-perfluoroalkyl-3-iodo quinolines in Suzuki, annulation, dehalogenation and carboxylation reactions. Antimalarial activity of the 2-perfluoroalkyl-3-iodoquinolines is discussed.