Rhodium-catalysed regio- and enantioselective Suzuki-Miyaura cross-coupling reactions
<p>In this thesis, we describe a range of rhodium-catalysed regio- and enantioselective Suzuki-Miyaura type cross-coupling reactions. Brief elaborations of products and modifications of drug molecules and natural products are demonstrated to show the utilities of these methodologies.</p>...
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | English |
| Published: |
2023
|
| Subjects: |
| _version_ | 1797112577985085440 |
|---|---|
| author | Liu, K |
| author2 | Fletcher, S |
| author_facet | Fletcher, S Liu, K |
| author_sort | Liu, K |
| collection | OXFORD |
| description | <p>In this thesis, we describe a range of rhodium-catalysed regio- and enantioselective Suzuki-Miyaura type cross-coupling reactions. Brief elaborations of products and modifications of drug molecules and natural products are demonstrated to show the utilities of these methodologies.</p>
<p>In Chapter 1, transition-metal-catalysed asymmetric Suzuki-Miyaura cross-coupling reactions are introduced in sequence, categorised by transition-metal type. Recent highlights in this area are discussed and the future of asymmetric Suzuki-Miyaura cross-coupling reactions is outlined.</p>
<p>In Chapter 2, we present the rhodium-catalysed regio- and enantioselective Suzuki-Miyaura cross-coupling reactions between vinylethylene carbonate and (hetero)arylboronic acids. We proposed that the chelation of substrate would help the regiocontrol. Combined experimental and computational mechanistic studies reveal the formation of a six-membered rhoda-1,3-dioxa-2-one intermediate after S<sub>N</sub>2’ oxidative addition during catalytic cycle, which is crucial for the regio- and enantiocontrol.</p>
<p>In Chapter 3, the method shown in Chapter 2 is elaborated by changing the ligand and solvent. The reaction scope now includes methyl-substituted vinylethylene carbonate. Notably, this represents the first examples of acyclic quaternary stereogenic centres formations via Rh-catalysed cross-coupling reactions between racemic tertiary electrophiles and achiral nucleophiles. The synthetic utilities of this method are demonstrated with formal syntheses of drug candidate and natural products (+)-epilaurene and (−)-cuparene.</p>
<p>In Chapter 4, we describe a series of general and modular regio- and enantioselective allylic arylation reactions. Unlike Chapter 2 and Chapter 3, the regioselectivities in this chapter are completely controlled by the rhodium/ligand complex. This method consistently produced arylation products in high levels of yield and selectivities (typically >90% yield, >95% ee and >20:1 r.r.). The synthetic applicability of these transformations is demonstrated with late-stage-functionalisations of naproxen, (−)-citronellal, (−)-perillaldehyde and estrone.</p> |
| first_indexed | 2024-03-07T08:27:35Z |
| format | Thesis |
| id | oxford-uuid:65f5c363-c7bc-4de5-865c-f974377db87b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:27:35Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | oxford-uuid:65f5c363-c7bc-4de5-865c-f974377db87b2024-02-22T14:21:09ZRhodium-catalysed regio- and enantioselective Suzuki-Miyaura cross-coupling reactionsThesishttp://purl.org/coar/resource_type/c_db06uuid:65f5c363-c7bc-4de5-865c-f974377db87bChemistry, OrganicEnglishHyrax Deposit2023Liu, KFletcher, S<p>In this thesis, we describe a range of rhodium-catalysed regio- and enantioselective Suzuki-Miyaura type cross-coupling reactions. Brief elaborations of products and modifications of drug molecules and natural products are demonstrated to show the utilities of these methodologies.</p> <p>In Chapter 1, transition-metal-catalysed asymmetric Suzuki-Miyaura cross-coupling reactions are introduced in sequence, categorised by transition-metal type. Recent highlights in this area are discussed and the future of asymmetric Suzuki-Miyaura cross-coupling reactions is outlined.</p> <p>In Chapter 2, we present the rhodium-catalysed regio- and enantioselective Suzuki-Miyaura cross-coupling reactions between vinylethylene carbonate and (hetero)arylboronic acids. We proposed that the chelation of substrate would help the regiocontrol. Combined experimental and computational mechanistic studies reveal the formation of a six-membered rhoda-1,3-dioxa-2-one intermediate after S<sub>N</sub>2’ oxidative addition during catalytic cycle, which is crucial for the regio- and enantiocontrol.</p> <p>In Chapter 3, the method shown in Chapter 2 is elaborated by changing the ligand and solvent. The reaction scope now includes methyl-substituted vinylethylene carbonate. Notably, this represents the first examples of acyclic quaternary stereogenic centres formations via Rh-catalysed cross-coupling reactions between racemic tertiary electrophiles and achiral nucleophiles. The synthetic utilities of this method are demonstrated with formal syntheses of drug candidate and natural products (+)-epilaurene and (−)-cuparene.</p> <p>In Chapter 4, we describe a series of general and modular regio- and enantioselective allylic arylation reactions. Unlike Chapter 2 and Chapter 3, the regioselectivities in this chapter are completely controlled by the rhodium/ligand complex. This method consistently produced arylation products in high levels of yield and selectivities (typically >90% yield, >95% ee and >20:1 r.r.). The synthetic applicability of these transformations is demonstrated with late-stage-functionalisations of naproxen, (−)-citronellal, (−)-perillaldehyde and estrone.</p> |
| spellingShingle | Chemistry, Organic Liu, K Rhodium-catalysed regio- and enantioselective Suzuki-Miyaura cross-coupling reactions |
| title | Rhodium-catalysed regio- and enantioselective Suzuki-Miyaura cross-coupling reactions |
| title_full | Rhodium-catalysed regio- and enantioselective Suzuki-Miyaura cross-coupling reactions |
| title_fullStr | Rhodium-catalysed regio- and enantioselective Suzuki-Miyaura cross-coupling reactions |
| title_full_unstemmed | Rhodium-catalysed regio- and enantioselective Suzuki-Miyaura cross-coupling reactions |
| title_short | Rhodium-catalysed regio- and enantioselective Suzuki-Miyaura cross-coupling reactions |
| title_sort | rhodium catalysed regio and enantioselective suzuki miyaura cross coupling reactions |
| topic | Chemistry, Organic |
| work_keys_str_mv | AT liuk rhodiumcatalysedregioandenantioselectivesuzukimiyauracrosscouplingreactions |