New efficient enantioselective synthesis of 2-oxopiperazines: a practical access to chiral 3-substituted 2-oxopiperazines

The development of efficient and stereoselective methods to produce 1,4-disubstituted-2-oxopiperazine in enantiomerically pure form, from a readily available starting material is crucial. Herein, we report a reduction modification to our previously described synthesis of 1,4-disubstituted-2-oxopiperazine and also two original shortly accessed pathways. These new pathways can be routinely performed on a multigram scale and should rapidly find a place in the preparation of the 3-substituted-2-oxopiperazine diastereomers. Stereoselective alkylation of 1,4-disubstituted-2-oxopiperazine led to the corresponding (3S)-diastereomer or (3R)-diastereomer from the corresponding 2-oxopiperazine enantiomer with the chiral inductor substituted at the N-1 (1*) position, respectively, in good yield. (C) 2008 Elsevier Ltd. All rights reserved.