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.