Accessing Medium-Sized Rings via Vinyl Carbocation Intermediates
Abstract
Medium-sized rings (8–11-membered cycles) are often more challenging to synthesize than smaller rings (5–7-membered cycles) due to ring strain. Herein, we report a catalytic method for forming 8- and 9-membered rings that proceeds via the intramolecular Friedel–Crafts reactions of vinyl carbocation intermediates. These reactive species are generated catalytically through the ionization of vinyl toluenesulfonates by a Lewis acidic lithium cation–weakly coordinating anion salt.
Copyright and License
© 2024 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0.
Acknowledgement
Financial support for this work was generously provided by the National Institutes of Health, National Institute of General Medical Sciences (R35 GM12893 to H.M.N.), and the National Science Foundation (CHE-1764328 to K.N.H. and DGE-1650604 to S.P.). The authors thank the Caltech Center for Catalysis and Chemical Synthesis and Dr. Scott Virgil [California Institute of Technology (Caltech)] for assistance with mass spectrometry studies. The authors also thank the Mass Spectrometry facility at the University of California, Irvine, for mass spectrometry support and Dr. David Vander Velde (Caltech) and Dr. Ta-Chung Ong [University of California, Los Angeles (UCLA)] for NMR advice. Computational resources were provided by the UCLA Institute for Digital Research and Education. Z.Z. thanks Prof. Dr. Brian M. Stoltz (Caltech) and Prof. Dr. Theodor Agapie (Caltech) for useful discussions regarding the reaction mechanism studies.
Contributions
This paper was written through contributions of Z.Z., W.L., and H.M.N. Z.Z. and S.P. carried out the experimental work. W.L. carried out the computational work. J.E.B., D.A.D., and L.J.K. acquired and analyzed the microED data. M.S. acquired and analyzed the mass spectral data. K.N.H. supervised the computational work. Z.Z., S.P., and H.M.N. conceived the project. All authors have given approval to the final version of the manuscript.
Conflict of Interest
The authors declare no competing financial interest.
Data Availability
The data underlying this study are available in the published article and its Supporting Information.
CCDC 2221222 and 2252685–2252690 contain the supplementary crystallographic data for this paper.
Files
zhao-et-al-2024-accessing-medium-sized-rings-via-vinyl-carbocation-intermediates.pdf
Additional details
Identifiers
- ISSN
- 1523-7052
Related works
- Is supplemented by
- https://pubs.acs.org/doi/suppl/10.1021/acs.orglett.3c04014/suppl_file/ol3c04014_si_001.pdf (URL)
Funding
- National Institutes of Health
- R35 GM12893
- National Science Foundation
- CHE-1764328
- National Science Foundation
- NSF Graduate Research Fellowship DGE-1650604