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Updated: Mar 1, 2026

A Protocol for Safe Lithiation Reactions Using Organolithium Reagents
Published on: November 12, 2016
General Procedures for the Lithiation/Trapping of N-Boc Piperazines
James D Firth1, Peter O'Brien1, Leigh Ferris2
1Department of Chemistry, University of York , Heslington, York YO10 5DD, U.K.
Abstract:
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 were determined using in situ IR spectroscopy, and the previous complicated and diverse literature procedures were simplified. Subsequent trapping with electrophiles delivered a wide range of α-functionalized N-Boc piperazines. The scope and limitations of the distal N-group were investigated. The selective α- and β- arylation of N-Boc piperazines via lithiation/Negishi coupling is reported.
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