Exploring New Asymmetric Reactions Catalysed by Dicationic Pd(II) Complexes
Author(s)
Smith, Alexander
Type
Thesis
Abstract
Dicationic palladium(II) complexes have been shown to catalyse a number of important
asymmetric transformations including Michael, Mannich and aldol reactions. This PhD
thesis describes work undertaken to discover and develop novel applications of
dicationic palladium(II) complexes in asymmetric catalysis. The introductory chapter
outlines the advances in catalytic asymmetric α-functionlisation of β-ketoesters. This
includes both metal-catalysed and organocatalytic processes with reference to C-C, C-X
(X = F, Cl, Br), C-N, C-O and C-S bond forming reactions.
Chapter 2 discusses the work towards the synthesis of β-amino acids via Michael
reactions catalysed by Pd(II) complexes. These reactions failed to proceed with good
enantioselectivities, leading to the investigation of a number of related transformations.
In the following Chapter the reaction of β-ketoesters with oxaziridines to generate α-
hydroxy-β-ketoesters was discovered. Extensive screening of reaction parameters led to
the identification of dimethyldioxirane (DMD) as a superior oxidant for this reaction,
providing ee’s of up to 98%. Examining a range of substrates revealed several key
structural elements required for both reactivity and enantioselectivity.
Determination of the absolute stereochemistry of the products revealed opposite facial
selectivity to that reported in a number of related reactions. Chapter 4 discusses the
results of DFT calculations undertaken by a colleague (Prof H. S. Rzepa), to identify the
origins of stereoselectivity in the Pd(II) mediated α-hydroxylation of β-ketoesters with
DMD.
Chapter 5 discusses the investigation of carboxylated pyrrolidinones and succinimides
as substrates in the hydroxylation reaction. Successful α-hydroxylation provided access
to 3 classes of synthetically useful hydroxylated N-heterocyclic products with high
optical purity, and brief synthetic studies directed towards the natural product
Pramanicin were undertaken. The last Chapter contains experimental procedures and
characterisation data of all the compounds synthesised during the course of this project.
asymmetric transformations including Michael, Mannich and aldol reactions. This PhD
thesis describes work undertaken to discover and develop novel applications of
dicationic palladium(II) complexes in asymmetric catalysis. The introductory chapter
outlines the advances in catalytic asymmetric α-functionlisation of β-ketoesters. This
includes both metal-catalysed and organocatalytic processes with reference to C-C, C-X
(X = F, Cl, Br), C-N, C-O and C-S bond forming reactions.
Chapter 2 discusses the work towards the synthesis of β-amino acids via Michael
reactions catalysed by Pd(II) complexes. These reactions failed to proceed with good
enantioselectivities, leading to the investigation of a number of related transformations.
In the following Chapter the reaction of β-ketoesters with oxaziridines to generate α-
hydroxy-β-ketoesters was discovered. Extensive screening of reaction parameters led to
the identification of dimethyldioxirane (DMD) as a superior oxidant for this reaction,
providing ee’s of up to 98%. Examining a range of substrates revealed several key
structural elements required for both reactivity and enantioselectivity.
Determination of the absolute stereochemistry of the products revealed opposite facial
selectivity to that reported in a number of related reactions. Chapter 4 discusses the
results of DFT calculations undertaken by a colleague (Prof H. S. Rzepa), to identify the
origins of stereoselectivity in the Pd(II) mediated α-hydroxylation of β-ketoesters with
DMD.
Chapter 5 discusses the investigation of carboxylated pyrrolidinones and succinimides
as substrates in the hydroxylation reaction. Successful α-hydroxylation provided access
to 3 classes of synthetically useful hydroxylated N-heterocyclic products with high
optical purity, and brief synthetic studies directed towards the natural product
Pramanicin were undertaken. The last Chapter contains experimental procedures and
characterisation data of all the compounds synthesised during the course of this project.
Date Issued
2010-05
Date Awarded
2011-02
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Hii, Mimi
Creator
Smith, Alexander
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)