New synthetic pathway to diverse 2-substituted quinolines based on a multicomponent reaction: Solution-phase and solid-phase applications

Using Kobayashi's modification of the Grieco reaction, we were able to synthesize diverse 4-phenylthio-1,2,3,4-tetrahydroquinolines. These intermediates were oxidized and subsequently pyrolized to provide the corresponding quinolines. This new approach to 2-substituted quinolines was exemplified by liquid-phase production of a 25-member library. This was extended to solid-phase chemistry, starting from (L)-4-nitrophenylalanine on Wang resin, for production of a 16-member library. The latter compounds possess potentially interesting VLA-4 antagonist properties.