Hydrogen bonding phase-transfer catalysis: a new approach to asymmetric fluorination
<p><em>Chapter 1 – Introduction.</em> This chapter aims to highlight the importance of enantioselective fluorination in modern organic chemistry. The peculiar and sometimes contradictory properties of fluorine and fluorinated organic molecules are detailed along with examples of th...
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| Format: | Thesis |
| Language: | English |
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2020
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| _version_ | 1797078293855338496 |
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| author | Ibba, F |
| author2 | Gouverneur, V |
| author_facet | Gouverneur, V Ibba, F |
| author_sort | Ibba, F |
| collection | OXFORD |
| description | <p><em>Chapter 1 – Introduction.</em> This chapter aims to highlight the importance of enantioselective fluorination in modern organic chemistry. The peculiar and sometimes contradictory properties of fluorine and fluorinated organic molecules are detailed along with examples of their applications in the life sciences. The origin and the chemistry of fluorinating reagents are also discussed, with a particular emphasis on the fluoride anion’s uses and challenges in organic synthesis. Lastly, a summary of the current methodologies to access enantiopure fluorinated compounds is presented and discussed.</p>
<p><em>Chapter 2 – Hydrogen Bonding Mediated Asymmetric Nucleophilic Fluorination.</em> The work describes the development of the first protocol for asymmetric nucleophilic fluorination utilising alkali metal fluorides as fluorine source and a newly developed tridentate bis-urea organocatalyst. This novel strategy, named Hydrogen Bonding Phase-Transfer Catalysis (HB PTC), embraces the poor solubility of fluoride salts in organic solvents and their tendency to engage in hydrogen bonding to deliver fluorinated molecules in high enantioselectivity. </p>
<p><em>Chapter 3 – Structure and Conformation of bis-Urea Catalysts for Hydrogen Bonding Phase- Transfer Catalysis: Insights from NMR Spectroscopy.</em> A detailed NMR spectroscopic investigation is presented herein in order to unveil the mechanistic details of HB PTC. The work investigates the conformational preferences of bis-urea catalysts under relevant reaction conditions and their changes upon binding of fluoride. The characterisation of bis- ureas–TBAF and bis-ureas–CsF complexes, in solution and in the solid state, provides information about the hydrogen bonding network around fluoride. The detection of scalar coupling across hydrogen-bonding, <sup>1h</sup>J<sub>NH...F<sup>–</sup></sub>, represents a key parameter to study catalyst- fluoride interactions. NMR data are used to investigate how the structural features of the
catalysts influence the outcome of HB PTC fluorinations.</p> |
| first_indexed | 2024-03-07T00:29:59Z |
| format | Thesis |
| id | oxford-uuid:7f6ef2db-7711-47ec-8708-e944c1a253cf |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:29:59Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | oxford-uuid:7f6ef2db-7711-47ec-8708-e944c1a253cf2022-03-26T21:16:58ZHydrogen bonding phase-transfer catalysis: a new approach to asymmetric fluorinationThesishttp://purl.org/coar/resource_type/c_db06uuid:7f6ef2db-7711-47ec-8708-e944c1a253cfOrganic ChemistryEnglishHyrax Deposit2020Ibba, FGouverneur, V<p><em>Chapter 1 – Introduction.</em> This chapter aims to highlight the importance of enantioselective fluorination in modern organic chemistry. The peculiar and sometimes contradictory properties of fluorine and fluorinated organic molecules are detailed along with examples of their applications in the life sciences. The origin and the chemistry of fluorinating reagents are also discussed, with a particular emphasis on the fluoride anion’s uses and challenges in organic synthesis. Lastly, a summary of the current methodologies to access enantiopure fluorinated compounds is presented and discussed.</p> <p><em>Chapter 2 – Hydrogen Bonding Mediated Asymmetric Nucleophilic Fluorination.</em> The work describes the development of the first protocol for asymmetric nucleophilic fluorination utilising alkali metal fluorides as fluorine source and a newly developed tridentate bis-urea organocatalyst. This novel strategy, named Hydrogen Bonding Phase-Transfer Catalysis (HB PTC), embraces the poor solubility of fluoride salts in organic solvents and their tendency to engage in hydrogen bonding to deliver fluorinated molecules in high enantioselectivity. </p> <p><em>Chapter 3 – Structure and Conformation of bis-Urea Catalysts for Hydrogen Bonding Phase- Transfer Catalysis: Insights from NMR Spectroscopy.</em> A detailed NMR spectroscopic investigation is presented herein in order to unveil the mechanistic details of HB PTC. The work investigates the conformational preferences of bis-urea catalysts under relevant reaction conditions and their changes upon binding of fluoride. The characterisation of bis- ureas–TBAF and bis-ureas–CsF complexes, in solution and in the solid state, provides information about the hydrogen bonding network around fluoride. The detection of scalar coupling across hydrogen-bonding, <sup>1h</sup>J<sub>NH...F<sup>–</sup></sub>, represents a key parameter to study catalyst- fluoride interactions. NMR data are used to investigate how the structural features of the catalysts influence the outcome of HB PTC fluorinations.</p> |
| spellingShingle | Organic Chemistry Ibba, F Hydrogen bonding phase-transfer catalysis: a new approach to asymmetric fluorination |
| title | Hydrogen bonding phase-transfer catalysis: a new approach to asymmetric fluorination |
| title_full | Hydrogen bonding phase-transfer catalysis: a new approach to asymmetric fluorination |
| title_fullStr | Hydrogen bonding phase-transfer catalysis: a new approach to asymmetric fluorination |
| title_full_unstemmed | Hydrogen bonding phase-transfer catalysis: a new approach to asymmetric fluorination |
| title_short | Hydrogen bonding phase-transfer catalysis: a new approach to asymmetric fluorination |
| title_sort | hydrogen bonding phase transfer catalysis a new approach to asymmetric fluorination |
| topic | Organic Chemistry |
| work_keys_str_mv | AT ibbaf hydrogenbondingphasetransfercatalysisanewapproachtoasymmetricfluorination |