Hydrogen borrowing reactions of amino alcohols and the total synthesis of (–)-γ-lycorane
<p><b>Chapter 1: Introduction</b></p> <p>The introduction gives an overview of C–C bond forming reactions, highlighting their applications within the thesis. The historical development of C–C bond forming hydrogen borrowing reactions is then reviewed, with an emphasis...
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| Format: | Disertacija |
| Jezik: | English |
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2021
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| _version_ | 1826288346714865664 |
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| author | Hall, C |
| author2 | Donohoe, T |
| author_facet | Donohoe, T Hall, C |
| author_sort | Hall, C |
| collection | OXFORD |
| description | <p><b>Chapter 1: Introduction</b></p>
<p>The introduction gives an overview of C–C bond forming reactions, highlighting their applications
within the thesis. The historical development of C–C bond forming hydrogen borrowing reactions is
then reviewed, with an emphasis on work by the Donohoe group involving Ph* methyl ketone, as well
as examples in the chemical literature utilising earth-abundant metal catalysts. Finally, the role of
nitrogen-containing compounds within both natural products and pharmaceuticals is discussed.</p>
<p><b>Chapter 2: Hydrogen Borrowing Reactions of Aziridino Alcohols</b></p>
<p>The hydrogen borrowing reaction between various aziridino alcohols and Ph* methyl ketone is
explored, along with the formation of lactams upon removal of the Ph* group with Br2. A number of
N-Boc aziridines are synthesised and converted into their corresponding N-Bn aziridino alcohols via
structurally complex aziridino aldehyde dimers. The unexpected reactivity of trisubstituted aziridino
alcohols under hydrogen borrowing and Br2 cleavage conditions is also explored.</p>
<p><b>Chapter 3: Total Synthesis of (–)-γ-Lycorane</b></p>
<p>Utilising a key C–C bond forming hydrogen borrowing reaction, and a subsequent Br2-mediated Ph*
cleavage/lactam formation/ring opening cascade, the total synthesis of (–)-γ-Lycorane is completed in
9 steps, 4% overall yield and in 99:1 er. An alternative pericyclic approach to (–)-γ-Lycorane is also
explored, with a number of small and highly functionalised amine and aziridine substituted
cyclopentanes being successfully synthesised.</p>
<p><b>Chapter 4: Hydrogen Borrowing Reactions of Amino Alcohols</b></p>
<p>The hydrogen borrowing reaction between enantioenriched 1,2-amino alcohols, derived from both
natural and unnatural amino acids, and Ph* methyl ketone was investigated. The use of a bulky trityl
group was found to be effective in protecting the reaction intermediates against racemisation, leading
to the isolation of a large number of 1,4-amino ketone products in good yields and with high levels of
enantioenrichment. The use of HCl in HFIP was found to be effective for cleavage of both the Ph* and
trityl groups, giving 1,4-amino acid products in excellent yields and with no loss in enantioenrichment.</p>
<p>The use of column chromatography could be entirely avoided by performing the two steps in sequence
without intermediate purification.</p>
<p><b>Chapter 5: Experimental</b></p>
<p>This chapter contains the experimental procedures and spectroscopic data for all compounds
described within the thesis.</p>
<p><b>Appendix 1: X-Ray Crystallographic Data</b></p>
<p>The X-ray crystallographic data for compounds 312, 351, 368, 381, 410, 553, 591, 665, and 719 can be
found in this appendix.</p>
<p><b>Appendix 2: Experimental Procedures by Indi Marriott</b></p>
<p>Experimental data for compounds 411 and 410 prepared by Indi Marriot.</p>
<p><b>Appendix 3: References</b></p>
<p>The references cited within the thesis can be found in this appendix.</p>
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| first_indexed | 2024-03-07T02:12:19Z |
| format | Thesis |
| id | oxford-uuid:a111f74a-db15-4dbf-99c2-52c1cbbd460d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:12:19Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | oxford-uuid:a111f74a-db15-4dbf-99c2-52c1cbbd460d2022-03-27T02:10:20ZHydrogen borrowing reactions of amino alcohols and the total synthesis of (–)-γ-lycoraneThesishttp://purl.org/coar/resource_type/c_db06uuid:a111f74a-db15-4dbf-99c2-52c1cbbd460dChemistryCatalysisSynthesisEnglishHyrax Deposit2021Hall, CDonohoe, TDixon, DMarriott, I<p><b>Chapter 1: Introduction</b></p> <p>The introduction gives an overview of C–C bond forming reactions, highlighting their applications within the thesis. The historical development of C–C bond forming hydrogen borrowing reactions is then reviewed, with an emphasis on work by the Donohoe group involving Ph* methyl ketone, as well as examples in the chemical literature utilising earth-abundant metal catalysts. Finally, the role of nitrogen-containing compounds within both natural products and pharmaceuticals is discussed.</p> <p><b>Chapter 2: Hydrogen Borrowing Reactions of Aziridino Alcohols</b></p> <p>The hydrogen borrowing reaction between various aziridino alcohols and Ph* methyl ketone is explored, along with the formation of lactams upon removal of the Ph* group with Br2. A number of N-Boc aziridines are synthesised and converted into their corresponding N-Bn aziridino alcohols via structurally complex aziridino aldehyde dimers. The unexpected reactivity of trisubstituted aziridino alcohols under hydrogen borrowing and Br2 cleavage conditions is also explored.</p> <p><b>Chapter 3: Total Synthesis of (–)-γ-Lycorane</b></p> <p>Utilising a key C–C bond forming hydrogen borrowing reaction, and a subsequent Br2-mediated Ph* cleavage/lactam formation/ring opening cascade, the total synthesis of (–)-γ-Lycorane is completed in 9 steps, 4% overall yield and in 99:1 er. An alternative pericyclic approach to (–)-γ-Lycorane is also explored, with a number of small and highly functionalised amine and aziridine substituted cyclopentanes being successfully synthesised.</p> <p><b>Chapter 4: Hydrogen Borrowing Reactions of Amino Alcohols</b></p> <p>The hydrogen borrowing reaction between enantioenriched 1,2-amino alcohols, derived from both natural and unnatural amino acids, and Ph* methyl ketone was investigated. The use of a bulky trityl group was found to be effective in protecting the reaction intermediates against racemisation, leading to the isolation of a large number of 1,4-amino ketone products in good yields and with high levels of enantioenrichment. The use of HCl in HFIP was found to be effective for cleavage of both the Ph* and trityl groups, giving 1,4-amino acid products in excellent yields and with no loss in enantioenrichment.</p> <p>The use of column chromatography could be entirely avoided by performing the two steps in sequence without intermediate purification.</p> <p><b>Chapter 5: Experimental</b></p> <p>This chapter contains the experimental procedures and spectroscopic data for all compounds described within the thesis.</p> <p><b>Appendix 1: X-Ray Crystallographic Data</b></p> <p>The X-ray crystallographic data for compounds 312, 351, 368, 381, 410, 553, 591, 665, and 719 can be found in this appendix.</p> <p><b>Appendix 2: Experimental Procedures by Indi Marriott</b></p> <p>Experimental data for compounds 411 and 410 prepared by Indi Marriot.</p> <p><b>Appendix 3: References</b></p> <p>The references cited within the thesis can be found in this appendix.</p> |
| spellingShingle | Chemistry Catalysis Synthesis Hall, C Hydrogen borrowing reactions of amino alcohols and the total synthesis of (–)-γ-lycorane |
| title | Hydrogen borrowing reactions of amino alcohols and the total synthesis of (–)-γ-lycorane |
| title_full | Hydrogen borrowing reactions of amino alcohols and the total synthesis of (–)-γ-lycorane |
| title_fullStr | Hydrogen borrowing reactions of amino alcohols and the total synthesis of (–)-γ-lycorane |
| title_full_unstemmed | Hydrogen borrowing reactions of amino alcohols and the total synthesis of (–)-γ-lycorane |
| title_short | Hydrogen borrowing reactions of amino alcohols and the total synthesis of (–)-γ-lycorane |
| title_sort | hydrogen borrowing reactions of amino alcohols and the total synthesis of γ lycorane |
| topic | Chemistry Catalysis Synthesis |
| work_keys_str_mv | AT hallc hydrogenborrowingreactionsofaminoalcoholsandthetotalsynthesisofglycorane |