An Efficient Protocol for the Palladium-Catalyzed Asymmetric Decarboxylative Allylic Alkylation Using Low Palladium Concentrations and a Palladium(II) Precatalyst
Enantioselective catalytic allylic alkylation for the synthesis of 2-alkyl-2-allylcycloalkanones and 3,3-disubstituted pyrrolidinones, piperidinones and piperazinones has been previously reported by our laboratory. The efficient construction of chiral all-carbon quaternary centers by allylic alkylation was previously achieved with a catalyst derived in situ from zero-valent palladium sources and chiral phosphinooxazoline (PHOX) ligands. We now report an improved reaction protocol with broad applicability among different substrate classes in industry-compatible reaction media using loadings of palladium(II) acetate as low as 0.075 mol% and the readily available chiral PHOX ligands. The novel and highly efficient procedure enables facile scale-up of the reaction in an economical and sustainable fashion.
© 2015 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim. Received: March 13, 2015; Revised: May 21, 2015; Published online: July 14, 2015. We wish to thank the NIH-NIGMS (R01M080269), Amgen, AbbVie, Boehringer Ingelheim, and Caltech for financial support. This material is based upon work supported by the German National Academy of Sciences Leopoldina under Grant No. LPDS 2011-12 (fellowship to A.N.M.). D.C.D. is grateful for financial support from the National Science Foundation (Predoctoral Research Fellowship, No. DGE-1144469). We also wish to thank the National Cancer Institute of the National Institutes of Health under Award Number F31A174359 (fellowship to R.A.C.), and the Swiss National Science Foundation (SNSF, fellowship for M.L.). Y.N. thanks Toray Industries, Inc. for a postdoctoral fellowship. Dr. Scott Virgil is acknowledged for assistance with instrumentation. Dr. John A. Enquist and Dr. Nathaniel H. Sherden are acknowledged for preliminary experimental work related to these results. Dr. Douglas C. Behenna is acknowledged for insightful discussions.
Supplemental Material - adsc_201500253_sm_miscellaneous_information.pdf
Accepted Version - nihms768886.pdf