A selective one-step synthesis of tris N-alkylated cyclens

A general one-step synthesis for tris N-alkylated cyclens with good yield and unprecedented selectivity is presented. Tris and 1,4-bis N-alkylated cyclens, as the only two major products are isolated. Furthermore, according to the single crystal X-ray structures of tris and 1,4-bis N-alkylated cyclen 1 and 1a, one nitrogen atom on the cyclen ring can be protonated under this reaction condition, which prevents its further alkylation, and gives rise to the regioselectivity ultimately.