Electrophilic Activation of [1.1.1]Propellane for the Synthesis of Nitrogen‐Substituted Bicyclo[1.1.1]pentanes
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- Sarah Livesley
- Department of Chemistry University of Liverpool Crown Street Liverpool L69 7ZD UK
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- Alistair J. Sterling
- Chemistry Research Laboratory University of Oxford 12 Mansfield Road Oxford OX1 3TA UK
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- Craig M. Robertson
- Department of Chemistry University of Liverpool Crown Street Liverpool L69 7ZD UK
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- William R. F. Goundry
- Early Chemical Development Pharmaceutical Sciences, R&D AstraZeneca Macclesfield SK10 2NA UK
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- James A. Morris
- Syngenta International Research Centre Bracknell Berkshire RG42 6EY UK
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- Fernanda Duarte
- Chemistry Research Laboratory University of Oxford 12 Mansfield Road Oxford OX1 3TA UK
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- Christophe Aïssa
- Department of Chemistry University of Liverpool Crown Street Liverpool L69 7ZD UK
抄録
<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>
収録刊行物
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- Angewandte Chemie International Edition
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Angewandte Chemie International Edition 61 (2), 2021-11-26
Wiley