Asymmetric synthesis of 2,6-methylated piperazines

An intramolecular Mitsunobu cyclization or a highly stereoselective triflate alkylation is used to synthesize the complete series of enantiopure 2,6-methylated piperazines. By using any of the reaction, the dimethyl enantiomers (2R,6R)- and (2S,6S)-2,6-dimethylpiperazine are prepared. The trimethyl compounds (R)- and (S)-2,2,6-trimethylpiperazine are synthesized by an enantiospecific triflate alkylation and the (R)- and (S)-tert-butyl 2-methyl-1-piperazinecarboxylate by the Mitsunobu cyclization.