New late-stage strategies towards difluoromethylarenes
This thesis consists of the development of novel methodology to access difluoromethylated compounds both in the context of photoredox catalysis and fluorine-18 radiochemistry for Positron Emission Tomography (PET). First a general introduction to late-stage difluoromethylation will be showcased in &...
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| Format: | Thesis |
| Language: | English |
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2020
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| _version_ | 1797110633580199936 |
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| author | Sap, JBI |
| author2 | Gouverneur, V |
| author_facet | Gouverneur, V Sap, JBI |
| author_sort | Sap, JBI |
| collection | OXFORD |
| description | This thesis consists of the development of novel methodology to access difluoromethylated compounds both in the context of photoredox catalysis and fluorine-18 radiochemistry for Positron Emission Tomography (PET). First a general introduction to late-stage difluoromethylation will be showcased in <strong>Chapter I</strong>. In <strong>Chapter II</strong>, a metal-free visible light catalysed synthesis of difluoromethylarenes via a controlled hydrodefluorination of electron-poor trifluoromethylarenes is described. The reaction works both in batch and in flow and proves to be useful in the context of late-stage functionalisation. In <strong>Chapter III</strong>, a general introduction to PET is provided. General radiochemistry concepts are also introduced. In <strong>Chapter IV</strong>, a facile and robust radiochemical methodology for PET describing the synthesis of 18F-difluoromethylarenes from aryl boronic acids, ethyl bromofluoroacetate and cyclotron produced [18F]fluoride is presented. The two key steps involve a copper catalysed cross-coupling reaction using bench-stable aryl boronic acids to yield 2-fluoro-2-arylacetic acids in a two-step one-pot reaction followed by a manganese mediated 18F-fluorodecarboxylation to afford 18F-difluoromethylarenes in a streamlined fashion. <strong>Chapter V</strong> discusses the synthesis of the first 18F-difluorocarbene reagent and its application to react as a difluoromethylating reagent with phenols, thiophenols, N-heterocycles, and boronic acids. <strong>Chapter VI</strong> provides experimental data for compounds described within this thesis. |
| first_indexed | 2024-03-07T07:57:34Z |
| format | Thesis |
| id | oxford-uuid:77f6820f-9315-4e35-924f-a1e99718d7a9 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:57:34Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | oxford-uuid:77f6820f-9315-4e35-924f-a1e99718d7a92023-09-04T07:22:28ZNew late-stage strategies towards difluoromethylarenesThesishttp://purl.org/coar/resource_type/c_db06uuid:77f6820f-9315-4e35-924f-a1e99718d7a9Photoredox CatalysisOrganic ChemistryRadio chemistryEnglishHyrax Deposit2020Sap, JBIGouverneur, VThis thesis consists of the development of novel methodology to access difluoromethylated compounds both in the context of photoredox catalysis and fluorine-18 radiochemistry for Positron Emission Tomography (PET). First a general introduction to late-stage difluoromethylation will be showcased in <strong>Chapter I</strong>. In <strong>Chapter II</strong>, a metal-free visible light catalysed synthesis of difluoromethylarenes via a controlled hydrodefluorination of electron-poor trifluoromethylarenes is described. The reaction works both in batch and in flow and proves to be useful in the context of late-stage functionalisation. In <strong>Chapter III</strong>, a general introduction to PET is provided. General radiochemistry concepts are also introduced. In <strong>Chapter IV</strong>, a facile and robust radiochemical methodology for PET describing the synthesis of 18F-difluoromethylarenes from aryl boronic acids, ethyl bromofluoroacetate and cyclotron produced [18F]fluoride is presented. The two key steps involve a copper catalysed cross-coupling reaction using bench-stable aryl boronic acids to yield 2-fluoro-2-arylacetic acids in a two-step one-pot reaction followed by a manganese mediated 18F-fluorodecarboxylation to afford 18F-difluoromethylarenes in a streamlined fashion. <strong>Chapter V</strong> discusses the synthesis of the first 18F-difluorocarbene reagent and its application to react as a difluoromethylating reagent with phenols, thiophenols, N-heterocycles, and boronic acids. <strong>Chapter VI</strong> provides experimental data for compounds described within this thesis. |
| spellingShingle | Photoredox Catalysis Organic Chemistry Radio chemistry Sap, JBI New late-stage strategies towards difluoromethylarenes |
| title | New late-stage strategies towards difluoromethylarenes |
| title_full | New late-stage strategies towards difluoromethylarenes |
| title_fullStr | New late-stage strategies towards difluoromethylarenes |
| title_full_unstemmed | New late-stage strategies towards difluoromethylarenes |
| title_short | New late-stage strategies towards difluoromethylarenes |
| title_sort | new late stage strategies towards difluoromethylarenes |
| topic | Photoredox Catalysis Organic Chemistry Radio chemistry |
| work_keys_str_mv | AT sapjbi newlatestagestrategiestowardsdifluoromethylarenes |