General Procedures for the Lithiation/Trapping of N-Boc Piperazines

In order to provide α-substituted piperazines for early-stage medicinal chemistry studies, a simple, general synthetic approach is required. Here, we report the development of two general and simple procedures for the racemic lithiation/trapping of N-Boc piperazines. Optimum lithiation times have been determined using in situ IR spectroscopy and the previous complicated and diverse literature procedures have been simplified. Subsequent trapping with electrophiles delivered a wide range of α-functionalised N-Boc piperazines. The scope and limitations of the distal N-group has been investigated. The selective α- and β- arylation of N-Boc piperazines via lithiation/Negishi coupling is reported.