Abstract
Deprotonation of
N-Boc-
N′-alkylpiperazines and dynamic thermodynamic resolution (DTR) with a chiral ligand gave, after electrophilic quench, 2-substituted
N-Boc-
N′-alkylpiperazines with moderate yields and enantioselectivities.
Deprotonation of
N-Boc-
N′-alkylpiperazines with
sec-BuLi in Et
2O–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
°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.