Enantioselective Michael Spirocyclization of Palladium Enolates
Abstract
We report an enantioselective and diastereoselective Michael spirocyclization reaction of tetrasubstituted palladium enolates. This allows for the formation of adjacent all-carbon quaternary and tertiary stereocenters in good yield, dr, and ee. Various subsequent cyclization reactions enable access to a diverse range of tricyclic scaffolds. The mechanism of this transformation and the origins of stereoselectivity are investigated via quantum mechanics calculations.
Copyright and License
Supplemental Material
The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acscatal.5c02758.
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Cartesian coordinates of the calculated structures (ZIP)
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X-ray data for CCDC 2421482 (CIF)
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X-ray data for CCDC 2421483 (CIF)
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X-ray data for CCDC 2444207 (CIF)
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X-ray data for CCDC 2444208 (CIF)
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Additional experimental and computational details, characterization of new compounds (PDF)
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QM energies and analysis (XLSX)
Data Availability
CCDC Nos. 2421482, 2421483, 2444207, and 2444208 contain the supplementary data for this paper. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: + 44 1223 336033.
Conflict of Interest
The authors declare no competing financial interest.
Acknowledgement
The NIH-NIGMS (No. R35GM145239), Heritage Medical Research Investigators Program, and Caltech are thanked for the support of our research program. We also thank Dr. David VanderVelde (Caltech) for his NMR expertise, Dr. Mona Shahgoli, Dr. Scott C. Virgil, and Dr. Jay P. Barbor (Caltech) for their assistance with mass spectrometry and other instrumentation, Dr. Michael K. Takase (Caltech) for assistance and expertise with X-ray crystallography. The authors extend additional thanks to Prof. Alexander Q. Cusumano, Kevin J. Gonzalez, and Dr. Elliot F. Hicks for helpful discussions. C.S.S. and P.C. would like to thank the NSF GRFP for funding. W.A.G. thanks the NSF (No. CBET 2311117) for support. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. The authors thank the Caltech High Performance Computing Center for support.
Additional details
- National Institute of General Medical Sciences
- R35GM145239
- California Institute of Technology
- National Science Foundation Graduate Research Fellowship Program
- Division of Chemical, Bioengineering, Environmental, and Transport Systems
- 2311117
- Available
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2025-07-06
- Caltech groups
- Division of Chemistry and Chemical Engineering (CCE), Materials and Process Simulation Center
- Publication Status
- Published