Electrophilic Activation of [1.1.1]Propellane for the Synthesis of Nitrogen‐Substituted Bicyclo[1.1.1]pentanes
-
- Sarah Livesley
- Department of Chemistry University of Liverpool Crown Street Liverpool L69 7ZD UK
-
- Alistair J. Sterling
- Chemistry Research Laboratory University of Oxford 12 Mansfield Road Oxford OX1 3TA UK
-
- Craig M. Robertson
- Department of Chemistry University of Liverpool Crown Street Liverpool L69 7ZD UK
-
- William R. F. Goundry
- Early Chemical Development Pharmaceutical Sciences, R&D AstraZeneca Macclesfield SK10 2NA UK
-
- James A. Morris
- Syngenta International Research Centre Bracknell Berkshire RG42 6EY UK
-
- Fernanda Duarte
- Chemistry Research Laboratory University of Oxford 12 Mansfield Road Oxford OX1 3TA UK
-
- Christophe Aïssa
- Department of Chemistry University of Liverpool Crown Street Liverpool L69 7ZD UK
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>
Journal
-
- Angewandte Chemie International Edition
-
Angewandte Chemie International Edition 61 (2), 2021-11-26
Wiley
- Tweet
Details 詳細情報について
-
- CRID
- 1360017285981339520
-
- ISSN
- 15213773
- 14337851
-
- Data Source
-
- Crossref