Asymmetric Synthesis of Chiral Piperazines

Significance

Described here is a concise and modular asymmetric synthesis of N-aryl-2,6-di­substituted piperazine via a Pd-catalyzed carbo­amination reaction. The process allows the stereo­selective preparation of piperazine derivatives with different N1, C2, N4 and C6 groups starting from commercial amino acids. A 4:1 ratio of Pd₂(dba)₃ and P(2-furyl)₃ was found to be the best catalyst system in order to suppress the formation of the major side products B and C. Aryl bromides containing EWG and EDG were found to be effective coupling partners.