A short and efficient synthesis of N-aryl- and N-heteroaryl-N′-(arylalkyl)piperazines

A new synthesis of N-aryl- and N-heteroaryl-N'-(arylalkl)pipeazines using palladium-catalyzed amination of aryl bromicies and heteroaryl chlorides with mono N-benzyl- or N-(arylethyl)piperazines is reported. Most coupling processes proceed in high yield and good selectivity using either diadmantyl-n-butylphosphine (1), 2-(dicyclohexylphosphino)-2'-(N,N-dimethylamino)biphenyl (2), or 2-((di-tert-butylphosphino)biphenyl (3) as ligand. Applying an automated parallel synthesizer the preparation of a small library of potentially bioactive compounds is easily achieved. (C) 2004 Published by Elsevier Ltd.