Published August 16, 2024 | Published
Journal Article Open

Enantioselective Nickel-Catalyzed α-Spirocyclization of Lactones

Abstract

Herein we report a strategy for the enantioselective synthesis of spirocycles containing all-carbon quaternary centers via nickel-catalyzed intramolecular addition of lactone enolates to aryl nitriles. The established lactone α-spirocyclization efficiently and enantioselectively forges 5-, 6-, and 7-membered rings, performing best in the synthesis of 7-membered rings (up to 90% ee). This discovery represents an expansion of the synthetic toolkit for enantioselective spirocyclization, providing access to chiral, pharmaceutically relevant spirocyclic products.

Copyright and License

© 2024 The Authors. Published by American Chemical Society. 
This publication is licensed under CC-BY-NC-ND 4.0.

Data Availability

The data underlying this study are available in the published article and its Supporting Information.

CCDC 23530082353010 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via 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.

Funding

The NIH-NIGMS (R35GM145239), Heritage Medical Research Investigators Program, and Caltech are thanked for the support of our research program. The authors are grateful to the Caltech Presidential Postdoctoral Fellowship, National Science Foundation MPS-Ascend (2137996 for MR), and NIH MOSAIC K99/R00 (GM152819-02 for MR) programs for financial support.

Acknowledgement

Additionally, we thank Lucas Abounader for experimental assistance and Umicore for graciously providing the olefin metathesis catalysts used in this investigation.

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Additional details

Created:
September 4, 2024
Modified:
September 4, 2024