Dynamic thermodynamic resolution of lithiated N-Boc-N '-alkylpiperazines

作者：Robinson Steven P; Sheikh Nadeem S; Baxter Carl A; Coldham Iain^*

来源：Tetrahedron Letters, 2010, 51(28): 3642-3644.

DOI：10.1016/j.tetlet.2010.05.019

Deprotonation of N-Boc-N'-alkylpiperazines with sec-BuLi in Et(2)O-TMEDA gave the 2-lithio derivatives which were resolved in the presence of a chiral ligand. The best ligands for the asymmetric substitution were diamino-alkoxides that promoted a dynamic thermodynamic resolution (DTR) of the organolithium at -30 degrees C. Electrophilic quench gave enantiomerically enriched 2-substituted piperazines. Of a selection of piperazines, the N'-t-butyl derivative gave the best results, with the product N-Boc-N'-t-butyl-2-substituted piperazines being formed with enantiomer ratios up to 81:19.

• 出版日期2010-7-14