New reactivity and selectivity in rhodium-catalysed hydroacylation
<p>This thesis documents the development of two new rhodium(I)-catalysed methodologies. The first shows the use of 1,4-dicarbonyl systems in hydroacylation for the preparation of synthetically valuable alpha-N-amido ketones. The second method is a dynamic kinetic resolution process for the syn...
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| Format: | Thesis |
| Language: | English |
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2020
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| _version_ | 1817932655659843584 |
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| author | Pal, R |
| author2 | Willis, M |
| author_facet | Willis, M Pal, R |
| author_sort | Pal, R |
| collection | OXFORD |
| description | <p>This thesis documents the development of two new rhodium(I)-catalysed methodologies. The first shows the use of 1,4-dicarbonyl systems in hydroacylation for the preparation of synthetically valuable alpha-N-amido ketones. The second method is a dynamic kinetic resolution process for the synthesis of enantiomerically enriched 1,3-dicarbonyl compounds.</p>
<p><b>Chapter 1</b> introduces the concept of rhodium-catalysed hydroacylation and presents a literature review covering key developments in the field of intra- and intermolecular hydroacylation, with a focus on chelating aldehydes that can be used to overcome decarbonylation. The advancement of enantioselective hydroacylation reactions has also been briefly summarised in this chapter.</p>
<p><b>Chapter 2</b> describes that readily available alpha-N-amidoaldehydes are effective substrates for intermolecular Rh-catalysed alkyne hydroacylation reactions. The catalyst [Rh(dppe)(C<sub>6</sub>H<sub>5</sub>F)][BAr<sup>F</sup><sub>4</sub>], allows a broad range of aldehydes and alkynes to be used as substrates, delivering alpha-N-amido ketone products in high yields and high levels of regiocontrol. The use of alpha-N-amido aldehydes as substrates establishes that 6-membered rhodacyclic intermediates provide suitable chelating stability to enable productive hydroacylation.</p>
<p><b>Chapter 3</b> presents the development of enantioselective Rh-catalysed alkyne hydroacylation of beta-amido aldehydes via dynamic kinetic resolution. The method delivers enantiomerically enriched 1,3-dicarbonyl products in a highly enantioselective fashion with good yields and high regiocontrol, using a combination of cationtic Rh, commercially available (R)- DMMGarphos ligand and Cs<sub>2</sub>CO<sub>3</sub>. To the best our knowledge, this is the first example of dynamic kinetic resolution in intermolecular hydroacylation.</p>
<p><b>Chapter 4</b> summarises the research work done and the potential future work.</p>
<p><b>Chapter 5</b> documents the experimental data and procedures.</p> |
| first_indexed | 2024-03-06T20:37:19Z |
| format | Thesis |
| id | oxford-uuid:3310c874-aeba-4a4f-8078-a95bdb3c81c4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:41:22Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | oxford-uuid:3310c874-aeba-4a4f-8078-a95bdb3c81c42024-12-07T12:25:58ZNew reactivity and selectivity in rhodium-catalysed hydroacylationThesishttp://purl.org/coar/resource_type/c_db06uuid:3310c874-aeba-4a4f-8078-a95bdb3c81c4Metal-catalysisOrganic synthesisEnglishHyrax Deposit2020Pal, RWillis, M<p>This thesis documents the development of two new rhodium(I)-catalysed methodologies. The first shows the use of 1,4-dicarbonyl systems in hydroacylation for the preparation of synthetically valuable alpha-N-amido ketones. The second method is a dynamic kinetic resolution process for the synthesis of enantiomerically enriched 1,3-dicarbonyl compounds.</p> <p><b>Chapter 1</b> introduces the concept of rhodium-catalysed hydroacylation and presents a literature review covering key developments in the field of intra- and intermolecular hydroacylation, with a focus on chelating aldehydes that can be used to overcome decarbonylation. The advancement of enantioselective hydroacylation reactions has also been briefly summarised in this chapter.</p> <p><b>Chapter 2</b> describes that readily available alpha-N-amidoaldehydes are effective substrates for intermolecular Rh-catalysed alkyne hydroacylation reactions. The catalyst [Rh(dppe)(C<sub>6</sub>H<sub>5</sub>F)][BAr<sup>F</sup><sub>4</sub>], allows a broad range of aldehydes and alkynes to be used as substrates, delivering alpha-N-amido ketone products in high yields and high levels of regiocontrol. The use of alpha-N-amido aldehydes as substrates establishes that 6-membered rhodacyclic intermediates provide suitable chelating stability to enable productive hydroacylation.</p> <p><b>Chapter 3</b> presents the development of enantioselective Rh-catalysed alkyne hydroacylation of beta-amido aldehydes via dynamic kinetic resolution. The method delivers enantiomerically enriched 1,3-dicarbonyl products in a highly enantioselective fashion with good yields and high regiocontrol, using a combination of cationtic Rh, commercially available (R)- DMMGarphos ligand and Cs<sub>2</sub>CO<sub>3</sub>. To the best our knowledge, this is the first example of dynamic kinetic resolution in intermolecular hydroacylation.</p> <p><b>Chapter 4</b> summarises the research work done and the potential future work.</p> <p><b>Chapter 5</b> documents the experimental data and procedures.</p> |
| spellingShingle | Metal-catalysis Organic synthesis Pal, R New reactivity and selectivity in rhodium-catalysed hydroacylation |
| title | New reactivity and selectivity in rhodium-catalysed hydroacylation |
| title_full | New reactivity and selectivity in rhodium-catalysed hydroacylation |
| title_fullStr | New reactivity and selectivity in rhodium-catalysed hydroacylation |
| title_full_unstemmed | New reactivity and selectivity in rhodium-catalysed hydroacylation |
| title_short | New reactivity and selectivity in rhodium-catalysed hydroacylation |
| title_sort | new reactivity and selectivity in rhodium catalysed hydroacylation |
| topic | Metal-catalysis Organic synthesis |
| work_keys_str_mv | AT palr newreactivityandselectivityinrhodiumcatalysedhydroacylation |