Livesley, Sarah, Sterling, Alistair J, Robertson, Craig M 
ORCID: 0000-0002-4789-7607, Goundry, William RF, Morris, James A, Duarte, Fernanda and Aissa, 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-INTERNATIONAL EDITION, 61 (2).
e202111291-.
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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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | [1.1.1]propellane, amination, bicyclo[1.1.1]pentane, bioisostere, halogen bond |
| Divisions: | Faculty of Science and Engineering > School of Physical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 03 Dec 2021 10:57 |
| Last Modified: | 18 Jan 2023 21:23 |
| DOI: | 10.1002/ange.202111291 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3144499 |
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