Journal article
Electrophilic activation of [1.1.1]propellane for the synthesis of nitrogen-substituted bicyclo[1.1.1]pentanes
- Abstract:
- Strategies commonly used for the synthesis of functionalised bicyclo[1.1.1]pentanes (BCP) rely on the reaction of [1.1.1]propellane with anionic or radical intermediates. In contrast, electrophilic activation has remained a considerable challenge due to the facile decomposition of BCP cations, which has severely limited the applications of this strategy. Herein, we report the electrophilic activation of [1.1.1]propellane in a halogen bond complex, which enables its reaction with electron-neutral nucleophiles such as anilines and azoles to give nitrogen-substituted BCPs that are prominent motifs in drug discovery. A detailed computational analysis indicates that the key halogen bonding interaction promotes nucleophilic attack without sacrificing cage stabilisation. Overall, our work rehabilitates electrophilic activation of [1.1.1]propellane as a valuable strategy for accessing functionalised BCPs.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.6MB, Terms of use)
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- Publisher copy:
- 10.1002/anie.202111291
Authors
+ Engineering and Physical Sciences Research Council
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- Funder identifier:
- https://ror.org/0439y7842
- Grant:
- EP/L015838/1
- EP/P020267/1
- Publisher:
- Wiley
- Journal:
- Angewandte Chemie International Edition More from this journal
- Volume:
- 61
- Issue:
- 2
- Article number:
- e202111291
- Publication date:
- 2021-11-26
- Acceptance date:
- 2021-10-27
- DOI:
- EISSN:
-
1521-3773
- ISSN:
-
1433-7851
- Pmid:
-
34705316
- Language:
-
English
- Keywords:
- Pubs id:
-
1207879
- Local pid:
-
pubs:1207879
- Deposit date:
-
2025-02-28
- ARK identifier:
Terms of use
- Copyright holder:
- Livesley et al.
- Copyright date:
- 2021
- Rights statement:
- © 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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