ISHC2015

A method for the synthesis of highly functionalized 4-aminoquinolines from sulphynamides and amides is presented. The amides are activated by triflic anhydride (Tf2O) and 2-chloropyridine (2-ClPy) and, as Movassaghi et al. have shown, can be used to prepare a wide range of heterocyclic structures.[1] Sulphynamides can be prepared using copper catalysis and alkyl bromides[2] and further derivatized by using Sonogashira chemistry.[3] The main challenge in existing quinoline syntheses is the functionalization at the C-2 and C-3 positions. By combining the Sonogashira approach with the ynamide/amide methodology a wide range of substitutions at C-3 is possible and the C-2 and C-5 to C-8 positions are also accessible. In order to show the broad applicability of the methodology, it was found that the ynamides also readily react with paracyclophane-based amides, creating very interesting planar chiral compounds.