Enantioselective synthesis of α-secondary and α-tertiary piperazin-2-ones and piperazines by catalytic asymmetric allylic alkylation.
The asymmetric palladium-catalyzed decarboxylative allylic alkylation of differentially N-protected piperazin-2-ones allows the synthesis of a variety of highly enantioenriched tertiary piperazine-2-ones. Deprotection and reduction affords the corresponding tertiary piperazines, which can be employed for the synthesis of medicinally important analogues. The introduction of these chiral tertiary piperazines resulted in imatinib analogues which exhibited comparable antiproliferative activity to that of their corresponding imatinib counterparts.
The Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E. California Blvd, MC 101-20, Pasadena, CA 91125 (USA).
Katerina M
KM
Korch
Christian
C
Eidamshaus
Douglas C
DC
Behenna
Sangkil
S
Nam
David
D
Horne
Brian M
BM
Stoltz
D000478:Alkylation; D000498:Allyl Compounds / Q000737:chemistry*; D002384:Catalysis; D010165:Palladium / Q000737:chemistry*; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000498:Allyl Compounds; D010879:Piperazines; D000077489:Piperazine; D010165:Palladium
allylic compounds; asymmetric catalysis; enantioselectivity; heterocycles; palladium