The synthesis of C2-symmetric 1,4,7-triazacyclononane ligands derived from chiral aziridines

An efficient synthetic route for the synthesis of C-2-symmetric derivatives of 1,4,7-triazacyclononanes 14 from chiral pool amino acids has been developed. These investigations have shown that competitive formation of piperazines 7 occurs when inappropriate nitrogen protecting groups are employed. It is apparent that the formation of the piperazines occurs as a result of an intramolecular nucleophilic attack followed by a beta-elimination. This appears to only be relevant for the formation of the [9]-N-3 ring, as the larger [12]-N-4 macrocycle, 11, is formed via a Richman-Atkins cyclisation in the presence of the same benzylic protected nitrogen atom. The single crystal X-ray structures of piperazine 7a and 1,4,7-triazacyclononanes 14a both reveal that weak intermolecular C-H...O=S interactions occur in the solid state in these systems.