Asymmetric synthesis of Trans-2,5-dimethylpyrrolidine

A new synthetic route to (2S,5S)-dimethylpyrrolidine 1, which can also be applied to the synthesis of the (2R,5R)-enantiomer, has been developed. The C2-symmetric pyrrolidine can be obtained enantiomerically pure (e.e. ⩾ 97%) in 15% overall yield starting from a mixture of isomers of 2,5-hexanediol, via a short reaction sequence using (S)-α-methylbenzylamine as a chiral auxiliary. The crystal and molecular structure of (S)-2′-phenyl-N-ethyl-(2S,5S)-dimethylpyrrolidine picrate 5, showing an antiparallel stacking of the picrate units, is also reported.