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Deacylation-aided C–H alkylative annulation through C–C cleavage of unstrained ketones

Zhou, Xukai and Xu, Yan and Dong, Guangbin (2021) Deacylation-aided C–H alkylative annulation through C–C cleavage of unstrained ketones. Nature Catalysis, 4 (8). pp. 703-710. ISSN 2520-1158. doi:10.1038/s41929-021-00661-7. https://resolver.caltech.edu/CaltechAUTHORS:20210526-113612996

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Abstract

Arene- and heteroarene-fused rings are pervasive in biologically active molecules. Direct annulation between a C–H bond on the aromatic core and a tethered alkyl moiety provides a straightforward approach to access these scaffolds; however, such a strategy is often hampered by the need of special reactive groups and/or less compatible cyclization conditions. It would be synthetically appealing if a common native functional group can be used as a handle to enable a general C–H annulation with diverse aromatic rings. Here, we show a deacylative annulation strategy for preparing a large variety of aromatic-fused rings from linear simple ketone precursors. The reaction starts with homolytic cleavage of the ketone α C–C bond via a pre-aromatic intermediate, followed by a radical-mediated dehydrogenative cyclization. Using widely available ketones as the robust radical precursors, this deconstructive approach allows streamlined assembly of complex polycyclic structures with broad functional group tolerance.


Item Type:Article
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URLURL TypeDescription
https://doi.org/10.1038/s41929-021-00661-7DOIArticle
https://rdcu.be/crlINPublisherFree ReadCube access
ORCID:
AuthorORCID
Zhou, Xukai0000-0003-0053-5075
Xu, Yan0000-0003-2808-7964
Dong, Guangbin0000-0003-1331-6015
Additional Information:© 2021 Nature Publishing Group. Received 13 December 2020; Accepted 01 July 2021; Published 02 August 2021. This work was supported by NIGMS (grant no. 2R01GM109054). X.Z. thanks the International Talent Training Project of Dalian Institute of Chemical Physics for financial support. Umicore AG & Co KG is acknowledged for a donation of Ir salts. We thank J. Wang for helpful discussions. Data availability: Details about materials and methods, experimental procedures and characterization data are available in the Supplementary Information. Additional data are available from the corresponding authors upon request. Author Contributions: X.Z, Y.X. and G.D. conceived and designed the experiments. X.Z. and Y.X. performed the experiments. X.Z., Y.X. and G.D. co-wrote the manuscript. The authors declare no competing interests. Peer review information: Nature Catalysis thanks Laurent Chabaud, Zhiwei Zuo and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
Funders:
Funding AgencyGrant Number
NIH2R01GM109054
Dalian Institute of Chemical PhysicsUNSPECIFIED
Subject Keywords:Homogeneous catalysis; Synthetic chemistry methodology
Issue or Number:8
DOI:10.1038/s41929-021-00661-7
Record Number:CaltechAUTHORS:20210526-113612996
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210526-113612996
Official Citation:Zhou, X., Xu, Y. & Dong, G. Deacylation-aided C–H alkylative annulation through C–C cleavage of unstrained ketones. Nat Catal 4, 703–710 (2021). https://doi.org/10.1038/s41929-021-00661-7
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:109257
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:02 Aug 2021 21:10
Last Modified:31 Aug 2021 20:49

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