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Published July 15, 2025 | Version Supplemental material
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On the unexpected formation of [2.2.1]- and [2.1.1]homotriblattanes

Creators

  • 1. ROR icon California Institute of Technology
  • 2. ROR icon University of California, Irvine

Abstract

A new class of polycyclic caged compounds, the [2.n.1]homotriblattanes, is described herein. These scaffolds are accessed through a concise, three-step sequence featuring an unexpected radical cyclization of a-bromocyclopropyl ketones. Their structures and stereochemical assignments were confirmed by a combination of 2D NMR and X-ray crystallography. DFT studies provide mechanistic insight into their formation and the side products formed en route. This study expands the known chemical space of polycyclic cages and offers a new entry point into highly complex 3- dimensional frameworks.

Copyright and License

© 2025 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Acknowledgement

The NIH-NIGMS (R35GM145239), Heritage Medical Research Investigators Program, and Caltech, are thanked for their support of our research program. Preparative HPLC was performed with instrumentation at the Caltech Center for Catalysis and Chemical Synthesis, a facility of the Beckman Institute at Caltech. The Vanderwal lab gratefully acknowledges the NIH-NIGMS (R35GM145252) and the NSF (GRFP support for H.T.N.) We thank Dr. David VanderVelde (Caltech) for NMR expertise and Michael Takase for XRD assistance. We graciously thank Kevin J. Gonzalez and Alexander Q. Cusumano for many helpful discussions and Professor Andrei Kutateladze (University of Denver) for illuminating a critical structural typo in our original draft. A.E.S. would like to thank the NSF GRFP for funding.

Contributions

Adrian E. Samkian: Investigation. Hanh T. Nguyen: Investigation. Christopher D. Vanderwal: Supervision. Brian M. Stoltz: Supervision.

Conflict of Interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Brian M. Stoltz reports financial support was provided by National Institutes of Health. I, Brian M. Stoltz, am Editor in Chief of Tetrahedron, the sister journal to which we are submitting.

Supplemental Material

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Supplementary material 1. Crystallographic data for compound 4 (cif)

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Supplementary material 2. Crystallographic data for compound 22 (cif)

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Supplementary material 3. QM energies and analysis (xlsx)

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Supplementary material 4. Cartesian coordinates of the calculated structure of 17 (xyz)

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Supplementary material 5. Cartesian coordinates of the calculated structure of 17-18 (xyz)

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Supplementary material 6. Cartesian coordinates of the calculated structure of 18 (xyz)

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Supplementary material 7. Cartesian coordinates of the calculated structure of 18-19 (xyz)

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Supplementary material 8. Cartesian coordinates of the calculated structure of 19 (xyz)

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Supplementary material 9. Cartesian coordinates of the calculated structure of 19-20 (xyz)

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Supplementary material 10. Cartesian coordinates of the calculated structure of 20 (xyz)

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Supplementary material 11. Experimental Procedures, characterization data, and NMR spectra (PDF)

 

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Additional details

Identifiers

PMID
40453693
PMCID
PMC12121957

Related works

Describes
Journal Article: 40453693 (PMID)
Journal Article: PMC12121957 (PMCID)

Funding

National Institute of General Medical Sciences
R35GM145239
California Institute of Technology
National Institutes of Health
R35GM145252
National Science Foundation

Dates

Submitted
2025-03-12
Accepted
2025-04-07
Available
2025-04-11
Available online
Available
2025-05-14
Version of record

Caltech Custom Metadata

Caltech groups
Heritage Medical Research Institute, Division of Chemistry and Chemical Engineering (CCE)
Publication Status
Published