Controlling absolute stereochemistry in hydrogen borrowing catalysed alkylation
<p>Hydrogen borrowing catalysis has recently emerged as a powerful alternative strategy for C–C bond formation and represents a green alternative to typical alkylation methodologies. Described in this thesis are novel strategies for controlling the absolute stereochemistry in hydrogen borrowin...
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| Other Authors: | |
| Format: | Thesis |
| Language: | English |
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2023
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| _version_ | 1826313781742927872 |
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| author | Cheang, DMJ-Y |
| author2 | Donohoe, T |
| author_facet | Donohoe, T Cheang, DMJ-Y |
| author_sort | Cheang, DMJ-Y |
| collection | OXFORD |
| description | <p>Hydrogen borrowing catalysis has recently emerged as a powerful alternative strategy for C–C bond formation and represents a green alternative to typical alkylation methodologies. Described in this thesis are novel strategies for controlling the absolute stereochemistry in hydrogen borrowing catalysed alkylations. Chapter two details the enantioselective synthesis of β,β-disubstituted ketones, efficiently forming sterically hindered C(sp3)–C(sp3) carbon bonds. The key enantiodetermining step, controlling the β-stereogenic centre, is an asymmetric reduction of a tri-substituted enone. The β,β-disubstituted ketone products were further derivatised via Ph* cleavage to the corresponding amides, esters and alcohols showing no racemization of the newly installed stereogenic centre.</p>
<p>Chapters three and four describe the development of methods controlling the γ-centre via dynamic kinetic resolution. Acyclic systems were explored, namely the alkylation of Ph* methyl ketone with racemic 1,2-amino alcohols demonstrating proof-of-concept reactivity via DKR (chapter 3). Subsequently, two complementary syntheses of enantioenriched γ-substituted cyclohexanes were developed (chapter 4). Mechanistic experiments revealed that alkylation with 1,5-diols led to a regioisomeric mixture of enone intermediates resulting in reduced enantioselectivity. By employing linear alcohols, a single enone intermediate was formed that could be racemised efficiently at the γ-centre via formation of an extended enolate, resulting in a highly enantioselective DKR process.</p> |
| first_indexed | 2024-09-25T04:22:02Z |
| format | Thesis |
| id | oxford-uuid:5feb6140-d4c1-40bc-8eff-b7d08ad13b56 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:22:02Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | oxford-uuid:5feb6140-d4c1-40bc-8eff-b7d08ad13b562024-08-09T09:03:18ZControlling absolute stereochemistry in hydrogen borrowing catalysed alkylationThesishttp://purl.org/coar/resource_type/c_db06uuid:5feb6140-d4c1-40bc-8eff-b7d08ad13b56EnglishHyrax Deposit2023Cheang, DMJ-YDonohoe, T<p>Hydrogen borrowing catalysis has recently emerged as a powerful alternative strategy for C–C bond formation and represents a green alternative to typical alkylation methodologies. Described in this thesis are novel strategies for controlling the absolute stereochemistry in hydrogen borrowing catalysed alkylations. Chapter two details the enantioselective synthesis of β,β-disubstituted ketones, efficiently forming sterically hindered C(sp3)–C(sp3) carbon bonds. The key enantiodetermining step, controlling the β-stereogenic centre, is an asymmetric reduction of a tri-substituted enone. The β,β-disubstituted ketone products were further derivatised via Ph* cleavage to the corresponding amides, esters and alcohols showing no racemization of the newly installed stereogenic centre.</p> <p>Chapters three and four describe the development of methods controlling the γ-centre via dynamic kinetic resolution. Acyclic systems were explored, namely the alkylation of Ph* methyl ketone with racemic 1,2-amino alcohols demonstrating proof-of-concept reactivity via DKR (chapter 3). Subsequently, two complementary syntheses of enantioenriched γ-substituted cyclohexanes were developed (chapter 4). Mechanistic experiments revealed that alkylation with 1,5-diols led to a regioisomeric mixture of enone intermediates resulting in reduced enantioselectivity. By employing linear alcohols, a single enone intermediate was formed that could be racemised efficiently at the γ-centre via formation of an extended enolate, resulting in a highly enantioselective DKR process.</p> |
| spellingShingle | Cheang, DMJ-Y Controlling absolute stereochemistry in hydrogen borrowing catalysed alkylation |
| title | Controlling absolute stereochemistry in hydrogen borrowing catalysed alkylation |
| title_full | Controlling absolute stereochemistry in hydrogen borrowing catalysed alkylation |
| title_fullStr | Controlling absolute stereochemistry in hydrogen borrowing catalysed alkylation |
| title_full_unstemmed | Controlling absolute stereochemistry in hydrogen borrowing catalysed alkylation |
| title_short | Controlling absolute stereochemistry in hydrogen borrowing catalysed alkylation |
| title_sort | controlling absolute stereochemistry in hydrogen borrowing catalysed alkylation |
| work_keys_str_mv | AT cheangdmjy controllingabsolutestereochemistryinhydrogenborrowingcatalysedalkylation |