Aziridines and aziridinium intermediates in the asymmetric synthesis of beta-substituted-alpha-amino acids and 1,2,3,4-tetrahydroisoquinolines
<p>This thesis is concerned with the development of methodology for the regioselective ring-opening of aziridines and aziridinium intermediates and its subsequent application to the asymmetric synthesis of β-substituted-α-amino acids and 1,2,3,4-tetrahydroisoquinolines. <p>Chapter 1 int...
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| Format: | Thesis |
| Language: | English |
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2015
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| _version_ | 1826290388838645760 |
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| author | Frost, A |
| author2 | Davies, S |
| author_facet | Davies, S Frost, A |
| author_sort | Frost, A |
| collection | OXFORD |
| description | <p>This thesis is concerned with the development of methodology for the regioselective ring-opening of aziridines and aziridinium intermediates and its subsequent application to the asymmetric synthesis of β-substituted-α-amino acids and 1,2,3,4-tetrahydroisoquinolines. <p>Chapter 1 introduces methods for the formation of aziridines and aziridinium ions and focusses on their utility as intermediates in synthesis.</p> <p>Chapter 2 describes studies into the synthesis of aziridines from enantiopure α-hydroxy-β-amino esters and their subsequent conversion to the corresponding β-hydroxy-α-amino acids via either a regioselective ring-opening with Cl<sub>3</sub>CCO<sub>2</sub>H, or a rearrangement promoted by Cl3CCO2H. Application of this procedure to both <em>syn</em>- and <em>anti</em>-configured substrates enabled the syntheses of (<em>S,S</em>)-<em>allo</em>-threonine, (2R,3S)-threonine, (R,R)-3-hydroxyphenylalanine and (2<em>S</em>,3<em>R</em>)-3-hydroxyphenylalanine.</p> <p>Chapter 3 details attempts to truncate the synthesis described in Chapter 2 by investigating the synthesis of enantiopure <em>anti</em>-β-hydroxy-α-amino acids via the intermediacy of aziridinium ions. These studies culminated in the development of a regioselective and stereospecific one-pot aziridinium formation and ring-opening protocol, leading to the synthesis of a range of C(3)-aryl and C(3)-alkyl substituted <em>anti</em>-β-hydroxy-α-amino acids.</p> <p>Chapter 4 discusses the conversion of enantiopure <em>anti</em>-α-hydroxy-β-amino esters to <em>anti</em>-β-fluoro-α-amino esters via the regioselective and stereospecific ring-opening of an aziridinium intermediates <em>in situ</em>. The subsequent development of a one-pot deprotection strategy leads to a concise and expedient synthesis of <em>anti</em>-β-fluorophenylalanines. The extension of this methodology to access a representative <em>anti</em>-α,β-diamino acid is also demonstrated.</p> <p>Chapter 5 describes the development of a one-pot diastereoselective rearrangement of enantiopure α-hydroxy-β-amino esters to 1,2,3,4-tetrahydroisoquinolines. The substrate scope of this reaction manifold is examined and application to the asymmetric synthesis of enantiopure 1,2,3,4-tetrahydroisoquinolines also discussed.</p> <p>Chapter 6 contains full experimental procedures and characterisation data for all compounds synthesised in Chapters 2, 3, 4 and 5.</p> </p> |
| first_indexed | 2024-03-07T02:43:26Z |
| format | Thesis |
| id | oxford-uuid:ab3aa702-caab-4d20-9057-028258be5fdb |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:43:26Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | oxford-uuid:ab3aa702-caab-4d20-9057-028258be5fdb2022-03-27T03:20:37Z Aziridines and aziridinium intermediates in the asymmetric synthesis of beta-substituted-alpha-amino acids and 1,2,3,4-tetrahydroisoquinolines Thesishttp://purl.org/coar/resource_type/c_db06uuid:ab3aa702-caab-4d20-9057-028258be5fdbOrganic chemistryEnglishOxford University Research Archive - Valet2015Frost, ADavies, S<p>This thesis is concerned with the development of methodology for the regioselective ring-opening of aziridines and aziridinium intermediates and its subsequent application to the asymmetric synthesis of β-substituted-α-amino acids and 1,2,3,4-tetrahydroisoquinolines. <p>Chapter 1 introduces methods for the formation of aziridines and aziridinium ions and focusses on their utility as intermediates in synthesis.</p> <p>Chapter 2 describes studies into the synthesis of aziridines from enantiopure α-hydroxy-β-amino esters and their subsequent conversion to the corresponding β-hydroxy-α-amino acids via either a regioselective ring-opening with Cl<sub>3</sub>CCO<sub>2</sub>H, or a rearrangement promoted by Cl3CCO2H. Application of this procedure to both <em>syn</em>- and <em>anti</em>-configured substrates enabled the syntheses of (<em>S,S</em>)-<em>allo</em>-threonine, (2R,3S)-threonine, (R,R)-3-hydroxyphenylalanine and (2<em>S</em>,3<em>R</em>)-3-hydroxyphenylalanine.</p> <p>Chapter 3 details attempts to truncate the synthesis described in Chapter 2 by investigating the synthesis of enantiopure <em>anti</em>-β-hydroxy-α-amino acids via the intermediacy of aziridinium ions. These studies culminated in the development of a regioselective and stereospecific one-pot aziridinium formation and ring-opening protocol, leading to the synthesis of a range of C(3)-aryl and C(3)-alkyl substituted <em>anti</em>-β-hydroxy-α-amino acids.</p> <p>Chapter 4 discusses the conversion of enantiopure <em>anti</em>-α-hydroxy-β-amino esters to <em>anti</em>-β-fluoro-α-amino esters via the regioselective and stereospecific ring-opening of an aziridinium intermediates <em>in situ</em>. The subsequent development of a one-pot deprotection strategy leads to a concise and expedient synthesis of <em>anti</em>-β-fluorophenylalanines. The extension of this methodology to access a representative <em>anti</em>-α,β-diamino acid is also demonstrated.</p> <p>Chapter 5 describes the development of a one-pot diastereoselective rearrangement of enantiopure α-hydroxy-β-amino esters to 1,2,3,4-tetrahydroisoquinolines. The substrate scope of this reaction manifold is examined and application to the asymmetric synthesis of enantiopure 1,2,3,4-tetrahydroisoquinolines also discussed.</p> <p>Chapter 6 contains full experimental procedures and characterisation data for all compounds synthesised in Chapters 2, 3, 4 and 5.</p> </p> |
| spellingShingle | Organic chemistry Frost, A Aziridines and aziridinium intermediates in the asymmetric synthesis of beta-substituted-alpha-amino acids and 1,2,3,4-tetrahydroisoquinolines |
| title | Aziridines and aziridinium intermediates in the asymmetric synthesis of beta-substituted-alpha-amino acids and 1,2,3,4-tetrahydroisoquinolines |
| title_full | Aziridines and aziridinium intermediates in the asymmetric synthesis of beta-substituted-alpha-amino acids and 1,2,3,4-tetrahydroisoquinolines |
| title_fullStr | Aziridines and aziridinium intermediates in the asymmetric synthesis of beta-substituted-alpha-amino acids and 1,2,3,4-tetrahydroisoquinolines |
| title_full_unstemmed | Aziridines and aziridinium intermediates in the asymmetric synthesis of beta-substituted-alpha-amino acids and 1,2,3,4-tetrahydroisoquinolines |
| title_short | Aziridines and aziridinium intermediates in the asymmetric synthesis of beta-substituted-alpha-amino acids and 1,2,3,4-tetrahydroisoquinolines |
| title_sort | aziridines and aziridinium intermediates in the asymmetric synthesis of beta substituted alpha amino acids and 1 2 3 4 tetrahydroisoquinolines |
| topic | Organic chemistry |
| work_keys_str_mv | AT frosta aziridinesandaziridiniumintermediatesintheasymmetricsynthesisofbetasubstitutedalphaaminoacidsand1234tetrahydroisoquinolines |