Livesley, Sarah, Sterling, Alistair J 
ORCID: 0000-0002-3571-1094, Robertson, Craig M ORCID: 0000-0002-4789-7607, Goundry, William RF ORCID: 0000-0003-2869-5855, Morris, James A, Duarte, Fernanda ORCID: 0000-0002-6062-8209 and Aïssa, Christophe ORCID: 0000-0003-0750-9435
(2022)
Electrophilic Activation of [1.1.1]Propellane for the Synthesis of Nitrogen‐Substituted Bicyclo[1.1.1]pentanes.
Angewandte Chemie, 134 (2).
ISSN 0044-8249, 1521-3757
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Abstract
<jats:title>Abstract</jats:title><jats:p>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.</jats:p>
| Item Type: | Article |
|---|---|
| Divisions: | Faculty of Science and Engineering > School of Physical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 07 Feb 2022 14:30 |
| Last Modified: | 07 Dec 2024 22:41 |
| DOI: | 10.1002/ange.202111291 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3148420 |
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