Progress in arylpiperazine synthesis by the catalytic amination reaction.

Careful base and solvent optimization for catalytic amination is described. A Pd-catalyzed amination between some arylbromide and unprotected piperazine (1equiv) was efficiently carried out with Pd/BINAP catalyst in a toluene-DBU solvent system, which is useful for the one-pot preparation of unsymmetrical piperazine through amination and in-situ N-protection. Reaction with N-BOC-piperazine was also successful in toluene-DBU or more polar NMP with Cs(2)CO(3) as a key base. No reports have previously reported such solvent and base optimization in arylpiperazine synthesis.