Synthesis of Free NH 2-(Aminomethyl)indoles through Copper-Catalyzed Reaction of 3-(ortho-Trifluoroacetamidophenyl)-1-propargylic Alcohols with Amines and Palladium/Copper-Cocatalyzed Domino Three-Component Sonogashira Cross-Coupling/Cyclization/Substitution Reactions

Free NH 2-(aminomethyl) indoles have been prepared via copper-catalyzed cyclization of 3-(ortho-trifluoroacetamidophenyl)-1-propargylic alcohols in the presence of primary or secondary amines. The synthesis has been developed into a simple and very efficient domino three-component Sonogashira cross-coupling/cyclization/substitution process that, omitting the isolation of 3(ortho-trifluoroacetamidophenyl)-1-propargylic alcohols, provides access to this class of compounds by treating 2-iodotrifluoroacetanilides, propargylic alcohols, and primary or secondary amines with a copper/palladium catalyst system.