Electrophilic Activation of [1.1.1]Propellane for the Synthesis of Nitrogen‐Substituted Bicyclo[1.1.1]pentanes

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).

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<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 Sep 2023 17:13
DOI: 10.1002/ange.202111291
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3148420