Synthesis of N-Aryl Amine Derivatives Using Copper Salts Catalysts

Unsymmetrical piperazines are key constituents of many anti-psychotic pharmaceuticals and bioactive compounds. Given that the selective introduction of an aryl and alkyl motif onto the piperazine skeleton is not always straightforward, direct arylation or alkylation of 1,4-diaza-bicyclo[2.2.2]octane would obviate the inefficiencies associated with the preparation of these target valuable molecules. We have utilized alkyl chlorides as the alkyl source, aryl triflates as the active aryl source, and 1,4-diaza-bicyclo[2.2.2]octane for the synthesis of N-alkyl-N′-arylpiperazines. The optimum conditions are developed using CuCl and t-BuOLi in PEG-400. Substrates bearing electron-deficient as well as electron-rich groups were successfully coupled under the optimum reaction conditions.