A concise asymmetric synthesis of cis-2,6-disubstituted N-aryl piperazines via Pd-catalyzed carboamination reactions

A concise, modular, asymmetric synthesis of cis-2,6-disubstituted piperazines from readily available amino acid precursors is described. The key step in the synthesis is a Pd-catalyzed carboamination of a N-1-aryl-N-2-allyl-1,2-diamine with an aryl bromide. The products are obtained in 14-20:1 dr, with > 97% ee, and the key cyclizations are the first examples of six-membered ring formation via Pd-catalyzed carboamination reactions of unsaturated amines with aryl halides.