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.
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Received: August 27, 2014, Article first published online: 7 NOV 2014. We wish to thank the NIH-NIGMS (R01GM080269) for financial support. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE-1144469 (fellowship to K.M.K.). We also wish to thank the Deutsche Forschungsgemeinschaft (DFG postdoctoral fellowship to C.E.), Amgen, Abbott, Boehringer Ingelheim, and Caltech for financial support. Corey Reeves is acknowledged for providing allyl cyanoformate and for insightful discussions. Douglas Duquette is acknowledged for providing allyl 1H-imidazole-1-carboxylate reagents and for insightful discussions. Scott Virgil is acknowledged for assistance with instrumentation and insightful discussions.
Supplemental Material - anie_201408609_sm_miscellaneous_information.pdf
Accepted Version - nihms647069.pdf