Highly Flexible Synthesis of 2-Arylethylamine Derivatives

A new and highly flexible procedure for the synthesis of 2-arylethylamine derivatives is described. By the new procedure, the target compounds can be synthesized with high diversity in three steps from aryl halides, terminal alkynes, and primary amines. The reaction sequence starts with a palladium-catalyzed coupling of an aryl halide and a terminal alkyne (Sonogashira coupling). A subsequent Cp2TiMe2-catalyzed hydroamination of the obtained alkyl(aryl)alkyne, which takes place regioselectively in the 2-position, gives access to an α-arylketimine. A final reduction with NaBH3CN/ZnCl2·Et2O results in the formation of the desired 2-arylethylamine derivative. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)