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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Main Author: Wu, Xingxing
Other Authors: Robin Chi Yonggui
Format: Theses and Dissertations
Language:English
Published: 2017
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Online Access:http://hdl.handle.net/10356/72774
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.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
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Chemistry
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
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.
author2 Robin Chi Yonggui
author_facet Robin Chi Yonggui
Wu, Xingxing
format Theses and Dissertations
author Wu, Xingxing
author_sort Wu, Xingxing
title 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_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_sort development of new reactions and reagents in carbene-catalyzed addition of carbon and nitrogen nucleophiles to unsaturated acyl azolium intermediates
publishDate 2017
url http://hdl.handle.net/10356/72774
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