New methods for the construction of fluorinated cyclic amines and amides
In recent years, photoredox catalysis has emerged as a powerful tool for the synthesis of complex building blocks. Fluorine-containing saturated nitrogen heterocycles are desirable structures in medicinal and biological chemistry, as the incorporation of fluorine can be used to influence key propert...
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| Format: | Thesis (University of Nottingham only) |
| Language: | English |
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2022
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| Online Access: | https://eprints.nottingham.ac.uk/67503/ |
| _version_ | 1848800427912462336 |
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| author | Charlesworth, Natalie |
| author_facet | Charlesworth, Natalie |
| author_sort | Charlesworth, Natalie |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | In recent years, photoredox catalysis has emerged as a powerful tool for the synthesis of complex building blocks. Fluorine-containing saturated nitrogen heterocycles are desirable structures in medicinal and biological chemistry, as the incorporation of fluorine can be used to influence key properties of a compound such as conformation, basicity and bioavailability. This thesis explores the utilisation of a photoredox-catalysed cyclisation/hydrogen atom transfer reaction of bromodifluoroethylamines, using a modular, two-step approach.
The first chapter provides an introduction to photoredox catalysis, notable developments in the area and relevant examples from the literature of photoredox-mediated radical cyclisation reactions. Following this, the importance of fluorination in drug discovery is discussed, along with traditional methods for the introduction of the geminal difluoro- group.
The second chapter describes a photoredox radical cyclisation protocol using bromodifluoroethylamines, which are prepared through a three-component coupling. The reaction is applicable to a wide range of alkenyl- and alkynyl amines, and the utility of the products are demonstrated. Mechanistic investigations established the role of the tertiary amine base and the additional hydrogen-atom donor in the reactions. The success of the described approach relies on the strongly electron-withdrawing nature of fluorine, which prevents oxidation of the amine substrates and products under the reaction conditions. This eliminates the need for electron-withdrawing protecting groups on nitrogen and promotes cyclisation.
The third chapter builds on the developed photoredox catalysed cyclisation for the mild and efficient synthesis of γ- and δ-lactams. The protocol is applicable to a range of amide substrates, and a mechanism for the reaction is proposed, supported by computational calculations. |
| first_indexed | 2025-11-14T20:51:24Z |
| format | Thesis (University of Nottingham only) |
| id | nottingham-67503 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T20:51:24Z |
| publishDate | 2022 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-675032022-08-02T04:40:08Z https://eprints.nottingham.ac.uk/67503/ New methods for the construction of fluorinated cyclic amines and amides Charlesworth, Natalie In recent years, photoredox catalysis has emerged as a powerful tool for the synthesis of complex building blocks. Fluorine-containing saturated nitrogen heterocycles are desirable structures in medicinal and biological chemistry, as the incorporation of fluorine can be used to influence key properties of a compound such as conformation, basicity and bioavailability. This thesis explores the utilisation of a photoredox-catalysed cyclisation/hydrogen atom transfer reaction of bromodifluoroethylamines, using a modular, two-step approach. The first chapter provides an introduction to photoredox catalysis, notable developments in the area and relevant examples from the literature of photoredox-mediated radical cyclisation reactions. Following this, the importance of fluorination in drug discovery is discussed, along with traditional methods for the introduction of the geminal difluoro- group. The second chapter describes a photoredox radical cyclisation protocol using bromodifluoroethylamines, which are prepared through a three-component coupling. The reaction is applicable to a wide range of alkenyl- and alkynyl amines, and the utility of the products are demonstrated. Mechanistic investigations established the role of the tertiary amine base and the additional hydrogen-atom donor in the reactions. The success of the described approach relies on the strongly electron-withdrawing nature of fluorine, which prevents oxidation of the amine substrates and products under the reaction conditions. This eliminates the need for electron-withdrawing protecting groups on nitrogen and promotes cyclisation. The third chapter builds on the developed photoredox catalysed cyclisation for the mild and efficient synthesis of γ- and δ-lactams. The protocol is applicable to a range of amide substrates, and a mechanism for the reaction is proposed, supported by computational calculations. 2022-08-02 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en cc_by https://eprints.nottingham.ac.uk/67503/1/Natalie%20Charlesworth%20Thesis%20Post-Viva%20Corrections.pdf Charlesworth, Natalie (2022) New methods for the construction of fluorinated cyclic amines and amides. PhD thesis, University of Nottingham. Fluorinated cyclic amines Amides |
| spellingShingle | Fluorinated cyclic amines Amides Charlesworth, Natalie New methods for the construction of fluorinated cyclic amines and amides |
| title | New methods for the construction of fluorinated cyclic amines and amides |
| title_full | New methods for the construction of fluorinated cyclic amines and amides |
| title_fullStr | New methods for the construction of fluorinated cyclic amines and amides |
| title_full_unstemmed | New methods for the construction of fluorinated cyclic amines and amides |
| title_short | New methods for the construction of fluorinated cyclic amines and amides |
| title_sort | new methods for the construction of fluorinated cyclic amines and amides |
| topic | Fluorinated cyclic amines Amides |
| url | https://eprints.nottingham.ac.uk/67503/ |