Enantioselective synthesis of α-secondary and α-tertiary piperazin-2-ones and piperazines by catalytic asymmetric allylic alkylation

Angew Chem Int Ed Engl. 2015 Jan 2;54(1):179-83. doi: 10.1002/anie.201408609. Epub 2014 Nov 7.

Abstract

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.

Keywords: allylic compounds; asymmetric catalysis; enantioselectivity; heterocycles; palladium.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alkylation
  • Allyl Compounds / chemistry*
  • Catalysis
  • Palladium / chemistry*
  • Piperazine
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry
  • Stereoisomerism

Substances

  • Allyl Compounds
  • Piperazines
  • Piperazine
  • Palladium