A quick and efficient route to substituted quinolines by electrophilic cyclization of 1-(2-aminoaryl)-2-yn-1-ols

Abstract

A practical method for the synthesis of substituted quinolines from 2-aminoarylketones (via 1-(2-aminoaryl)-2-yn-1-ols) using mild and simple reaction conditions is described. A study of several electrophiles in various reaction conditions is presented. Out of three electrophilic iodine sources (I₂, NIS and ICl) studied, I₂ was found to work efficiently for the synthesis of 3-iodoquinolines. Several Brønsted acids (pTSA, PPTS, AcOH, TFA, HCl) were able to catalyze the formation of 2,4-substituted quinolines from the same starting materials. Good to excellent overall yields were observed with both aromatic and aliphatic substitutions at the reaction center.