Synthesis of camphor derived ligands for applications in asymmetric catalysis.
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Date
2009
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Abstract
Chiral monoterpenes such as camphor have been widely used in the development of asymmetric
catalysts with varying degrees of success. Pyridyl N-donor ligands derived from camphor have been
extensively studied and have proven to be very successful. C3 pendant pyridyl alcohol ligands have
been neglected until this study. Herein the synthesis of a series of six novel C3 pendant ligands is
described. The ligands were synthesised in six steps (seven for ligand 4) using R-(+)-camphor as the starting material. Two alternative methods for the synthesis were investigated with the second method
(Method B) proving to be superior. Several difficulties with regards to regioisomers and
diastereomers were overcome in establishing the procedure for the synthesis of the ligands. The final
compounds were successfully synthesised in moderate yields with absolute regio- and stereo-control.
The ligands were evaluated as chiral catalysts in a series of different reactions. The first of these was
the alkylation of a series of aldehydes using diethylzinc. This reaction was investigated in order to
compare the efficacy of the novel compounds to previous camphor derived pyridyl alcohol ligands.
All previous molecules of this type have been evaluated as catalysts in this reaction with varying
degrees of success. The novel ligands successfully catalysed this reaction with moderate to good
enantioselectivity (up to 85% ee). The results obtained showed these compounds to be significantly
superior to a previous analogous C2 pendant β-amino alcohol reported in literature. The results were also comparable to other camphor derived pyridyl alcohol ligands reported previously.
The synthesis of ligands 1-4 as well as their evaluation as catalysts in the alkylation of aldehydes with diethylzinc is discussed in detail in chapter 2 (Paper 1).
The second reaction in which the ligands were evaluated was the Henry (Nitroaldol) reaction. This
reaction has not seen many camphor derived ligands applied as catalysts. Two additional derivatives
(5-6) were synthesized and all the compounds were screened as catalysts in this reaction. The ligands
successfully catalyzed the reaction with good to excellent yields but only moderate selectivity (up to
56% ee). The details of this evaluation are discussed in chapter 3 (Paper 2).
The final reaction in which the ligands were evaluated was the Diels-Alder reaction of 2-
acrolyloxazolidinone with cyclopentadiene. The reaction was again successfully catalysed in
moderate to good yields with good endo:exo selectivity but fairly poor stereoselectivity (up to 43%
ee). Computational models of the proposed complexes were developed in order to explain the poor
observed selectivity. The details of this study are reported in chapter 4 (Paper 3).
Chapter 5 (Paper 4) involves a NMR and computational investigation of some of the ligands.
Complete NMR elucidation using 2D NMR techniques were carried out for the selected ligands.
Optimisation of the ligands using high level DFT calculations was carried out in order to aid in the
visualisation of potential through space interactions within each molecule.
Description
Thesis (Ph.D.)-University of KwaZulu-Natal, 2009.
Keywords
Camphor., Asymmetric synthesis., Theses--Chemistry.