Copper-catalyzed cascade addition route to 2,3,4-trisubstituted quinoline derivatives

In honor of the memory of Professor Harry H. Wassermann, we present the synthesis of various substituted quinolines. The copper-catalyzed cascade addition of vinylmagnesium bromide on methyl anthranilate (1) provided quantitatively 1-[2-aminophenyl]pent-4-en-1-one (2). Although attempts to annulate the pyridine ring on this o-acyl aniline using transition metal catalysis with acetylenes were unsuccessful, a one-pot, solvent-free Friedlander synthesis provided 8 quinolines. In light of the potential for the double bond to serve in diversification chemistry as well as the importance of 4-substituted quinolines, this method offers effective access to a valuable class of medicinally relevant targets. (C) 2015 Elsevier Ltd. All rights reserved.