Development of new reactions and reagents in carbene-catalyzed addition of carbon and nitrogen nucleophiles to unsaturated acyl azolium intermediates
This thesis focuses on development of efficient protocols for access to advanced complex molecules enabled by N-heterocyclic carbene (NHC) catalyzed LUMO activation of enal or its ester derivatives, and discovery of polyhalide as simple organic oxidant for oxidative carbene catalysis. It contains fi...
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| Format: | Thesis |
| Language: | English |
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2017
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| Online Access: | http://hdl.handle.net/10356/72774 |
| _version_ | 1826124087797219328 |
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| author | Wu, Xingxing |
| author2 | Robin Chi Yonggui |
| author_facet | Robin Chi Yonggui Wu, Xingxing |
| author_sort | Wu, Xingxing |
| collection | NTU |
| description | This thesis focuses on development of efficient protocols for access to advanced complex molecules enabled by N-heterocyclic carbene (NHC) catalyzed LUMO activation of enal or its ester derivatives, and discovery of polyhalide as simple organic oxidant for oxidative carbene catalysis. It contains five parts:
Chapter 1 first gives a brief introduction to the history of asymmetric organocatalysis, followed by development of N-heterocyclic carbene (NHC) catalysis. This includes three main aspects, (a) catalysis involving umpolung acyl-anion, (b) homoenolate catalysis, (c) reactions involving acyl azolium intermediates. This chapter also illustrates the challenges and opportunities in NHC catalyzed reactions, especially in heteroatoms as nucleophiles for α, β-unsaturated acyl azolium and simple oxidants for oxidative NHC catalysis.
Chapter 2 describes a single-step, organocatalytic and enantioselective cascade process for access to a multi-cyclic lactone that constitutes the core structure of iridoids. This protocol shows the synthetic power of a NHC catalyst for the activation of a readily available and stable carboxylic ester to give the unsaturated acyl azolium intermediate.
Chapter 3 demonstrates an efficient protocol for the preparation of pyrazolidinone products via nucleophilic β-carbon amination of enals under oxidative NHC catalysis. The heterocycle adducts from the catalytic reaction can readily undergo further transformations to afford various useful functional molecules, such as pyrazolidines and β-amino acid derivatives.
Chapter 4 shows a novel and efficient cascade approach for the direct assembly of two privileged scaffolds (pyrrolidine and β-lactone) with good to excellent yield and enantioselectivity. This study sheds light on modulating the reactivity of nitrogen atom for challenging NHC-catalyzed asymmetric C-N bond formations.
Chapter 5 introduces polyhalide reagents as simple and inexpensive oxidants for oxidative NHC catalysis, providing efficient methods for functionalization of the α, β and γ atoms of aldehydes. The oxidative process involves multiple radical intermediates, and shall inspire new reaction development via NHC-catalyzed radical process. |
| first_indexed | 2024-10-01T06:14:56Z |
| format | Thesis |
| id | ntu-10356/72774 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:14:56Z |
| publishDate | 2017 |
| record_format | dspace |
| spelling | ntu-10356/727742023-02-28T23:49:13Z Development of new reactions and reagents in carbene-catalyzed addition of carbon and nitrogen nucleophiles to unsaturated acyl azolium intermediates Wu, Xingxing Robin Chi Yonggui School of Physical and Mathematical Sciences DRNTU::Science::Chemistry This thesis focuses on development of efficient protocols for access to advanced complex molecules enabled by N-heterocyclic carbene (NHC) catalyzed LUMO activation of enal or its ester derivatives, and discovery of polyhalide as simple organic oxidant for oxidative carbene catalysis. It contains five parts: Chapter 1 first gives a brief introduction to the history of asymmetric organocatalysis, followed by development of N-heterocyclic carbene (NHC) catalysis. This includes three main aspects, (a) catalysis involving umpolung acyl-anion, (b) homoenolate catalysis, (c) reactions involving acyl azolium intermediates. This chapter also illustrates the challenges and opportunities in NHC catalyzed reactions, especially in heteroatoms as nucleophiles for α, β-unsaturated acyl azolium and simple oxidants for oxidative NHC catalysis. Chapter 2 describes a single-step, organocatalytic and enantioselective cascade process for access to a multi-cyclic lactone that constitutes the core structure of iridoids. This protocol shows the synthetic power of a NHC catalyst for the activation of a readily available and stable carboxylic ester to give the unsaturated acyl azolium intermediate. Chapter 3 demonstrates an efficient protocol for the preparation of pyrazolidinone products via nucleophilic β-carbon amination of enals under oxidative NHC catalysis. The heterocycle adducts from the catalytic reaction can readily undergo further transformations to afford various useful functional molecules, such as pyrazolidines and β-amino acid derivatives. Chapter 4 shows a novel and efficient cascade approach for the direct assembly of two privileged scaffolds (pyrrolidine and β-lactone) with good to excellent yield and enantioselectivity. This study sheds light on modulating the reactivity of nitrogen atom for challenging NHC-catalyzed asymmetric C-N bond formations. Chapter 5 introduces polyhalide reagents as simple and inexpensive oxidants for oxidative NHC catalysis, providing efficient methods for functionalization of the α, β and γ atoms of aldehydes. The oxidative process involves multiple radical intermediates, and shall inspire new reaction development via NHC-catalyzed radical process. Doctor of Philosophy (SPMS) 2017-11-13T12:35:52Z 2017-11-13T12:35:52Z 2017 Thesis Wu, X. (2017). Development of new reactions and reagents in carbene-catalyzed addition of carbon and nitrogen nucleophiles to unsaturated acyl azolium intermediates. Doctoral thesis, Nanyang Technological University, Singapore. http://hdl.handle.net/10356/72774 10.32657/10356/72774 en 259 p. application/pdf |
| spellingShingle | DRNTU::Science::Chemistry Wu, Xingxing Development of new reactions and reagents in carbene-catalyzed addition of carbon and nitrogen nucleophiles to unsaturated acyl azolium intermediates |
| title | Development of new reactions and reagents in carbene-catalyzed addition of carbon and nitrogen nucleophiles to unsaturated acyl azolium intermediates |
| title_full | Development of new reactions and reagents in carbene-catalyzed addition of carbon and nitrogen nucleophiles to unsaturated acyl azolium intermediates |
| title_fullStr | Development of new reactions and reagents in carbene-catalyzed addition of carbon and nitrogen nucleophiles to unsaturated acyl azolium intermediates |
| title_full_unstemmed | Development of new reactions and reagents in carbene-catalyzed addition of carbon and nitrogen nucleophiles to unsaturated acyl azolium intermediates |
| title_short | Development of new reactions and reagents in carbene-catalyzed addition of carbon and nitrogen nucleophiles to unsaturated acyl azolium intermediates |
| title_sort | development of new reactions and reagents in carbene catalyzed addition of carbon and nitrogen nucleophiles to unsaturated acyl azolium intermediates |
| topic | DRNTU::Science::Chemistry |
| url | http://hdl.handle.net/10356/72774 |
| work_keys_str_mv | AT wuxingxing developmentofnewreactionsandreagentsincarbenecatalyzedadditionofcarbonandnitrogennucleophilestounsaturatedacylazoliumintermediates |