Studies towards the development of novel multidentate ligands
- Authors: Magqi, Nceba
- Date: 2007
- Subjects: Density functionals , Ligands , Ligands -- Design , Ligands -- Analysis , Camphor
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4358 , http://hdl.handle.net/10962/d1005023 , Density functionals , Ligands , Ligands -- Design , Ligands -- Analysis , Camphor
- Description: In this study, attention has been given to the design and synthesis of novel multidentate ligands for use in the construction of ruthenium-based metathesis catalysts, and their chelating potential has been explored by computer modelling at the Density Functional Theory (DFT) level. Both Kemp’s triacid (1,3,5-trimethyl-1,3,5-cyclohexanetricarboxylic acid) and D-(+)-camphor have been investigated as molecular scaffolds for the development of such ligands. However selective elaboration of the functional groups in Kemp’s triacid proved difficult to achieve, and the research has focused on the development of camphor derivatives. The synthesis of the camphor-based ligands has involved C-8 functionalisation and ring-opening of the bicyclic system to afford tridentate products. The formation of 9-iodocamphorquinone bis(ethylene ketal) together with the desired product, the 8-iodo isomer, has been confirmed by single crystal X-ray analysis of both compounds. Formation of the 9-iodo analogue has provided new insights into the intramolecular rearrangement of camphor skeleton, and the mechanistic implications have been assessed by coset analysis. Attempts to effect nucleophilic displacement of the 8-halogeno groups by nucleophilic donor moieties proved unexpectedly difficult and, coupled with the susceptibility of the carbonyl groups to nucleophilic attack, has led to the formation of novel tricyclic products, viz., 1,6-dimethyl-3-(2-pyridylamino)-4-oxatricyclo[4.3.0.0[superscript 3,7]]-2-nonanone and 6,7-dimethyl-3-(2-pyridylamino)-4-oxatricyclo -[4.3.0.0[superscript 3,7]]-2-nonanone. However the diphenylphosphine group was successfully introduced at C-8 and oxidative ring-opening of the camphor skeleton has afforded the tridentate ligands, 2-(diphenylphosphinoylmethyl)-1,2-dimethyl-1,3-cyclopentanedicarboxylic acid and 2-(diphenylphosphinoylmethyl)-1,3-bis(hydroxymethyl)1,2-dimethylcyclopentane. One- and two-dimensional NMR and, where appropriate, high-resolution MS methods have been used to characterise the products. Three [superscript 13]C NMR chemical shift prediction programmes, viz., ChemWindow and the MODGRAPH neural network and HOSE (Hierachially Ordered Spherical description of Environment), have been applied to representative compounds to assess their efficacy. While the predicted shifts correlated reasonably well with the experimental data, they proved to be insufficiently accurate to differentiate the isomeric systems examined.
- Full Text:
- Date Issued: 2007
- Authors: Magqi, Nceba
- Date: 2007
- Subjects: Density functionals , Ligands , Ligands -- Design , Ligands -- Analysis , Camphor
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4358 , http://hdl.handle.net/10962/d1005023 , Density functionals , Ligands , Ligands -- Design , Ligands -- Analysis , Camphor
- Description: In this study, attention has been given to the design and synthesis of novel multidentate ligands for use in the construction of ruthenium-based metathesis catalysts, and their chelating potential has been explored by computer modelling at the Density Functional Theory (DFT) level. Both Kemp’s triacid (1,3,5-trimethyl-1,3,5-cyclohexanetricarboxylic acid) and D-(+)-camphor have been investigated as molecular scaffolds for the development of such ligands. However selective elaboration of the functional groups in Kemp’s triacid proved difficult to achieve, and the research has focused on the development of camphor derivatives. The synthesis of the camphor-based ligands has involved C-8 functionalisation and ring-opening of the bicyclic system to afford tridentate products. The formation of 9-iodocamphorquinone bis(ethylene ketal) together with the desired product, the 8-iodo isomer, has been confirmed by single crystal X-ray analysis of both compounds. Formation of the 9-iodo analogue has provided new insights into the intramolecular rearrangement of camphor skeleton, and the mechanistic implications have been assessed by coset analysis. Attempts to effect nucleophilic displacement of the 8-halogeno groups by nucleophilic donor moieties proved unexpectedly difficult and, coupled with the susceptibility of the carbonyl groups to nucleophilic attack, has led to the formation of novel tricyclic products, viz., 1,6-dimethyl-3-(2-pyridylamino)-4-oxatricyclo[4.3.0.0[superscript 3,7]]-2-nonanone and 6,7-dimethyl-3-(2-pyridylamino)-4-oxatricyclo -[4.3.0.0[superscript 3,7]]-2-nonanone. However the diphenylphosphine group was successfully introduced at C-8 and oxidative ring-opening of the camphor skeleton has afforded the tridentate ligands, 2-(diphenylphosphinoylmethyl)-1,2-dimethyl-1,3-cyclopentanedicarboxylic acid and 2-(diphenylphosphinoylmethyl)-1,3-bis(hydroxymethyl)1,2-dimethylcyclopentane. One- and two-dimensional NMR and, where appropriate, high-resolution MS methods have been used to characterise the products. Three [superscript 13]C NMR chemical shift prediction programmes, viz., ChemWindow and the MODGRAPH neural network and HOSE (Hierachially Ordered Spherical description of Environment), have been applied to representative compounds to assess their efficacy. While the predicted shifts correlated reasonably well with the experimental data, they proved to be insufficiently accurate to differentiate the isomeric systems examined.
- Full Text:
- Date Issued: 2007
Applications of camphor-derived chiral auxiliaries in the asymmetric synthesis of α-amino acids and other systems
- Authors: Matjila, Joseph Moemise
- Date: 1998-04
- Subjects: Imino compounds , Alpha-amino acid , Asymmetric synthesis , Camphor , Enantioselective catalysis , Baylis–Hillman reaction
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/191501 , vital:45106
- Description: A viable synthetic route to camphor-derived imino lactones as precursors for the asymmetric synthesis of a-amino acids has been established. Several synthetic strategies have been investigated and the required regioisomeric imino lactones were finally obtained via the step-wise condensation of JV-(carbobenzyloxy)glycine with the a-ketols, 3-exo-hydroxycamphor and 2-exo- hydroxy-3-bomanone. Enolates of the camphor imino lactones, generated using potassium tert- butoxide, were reacted with a range of alkyl halides. Dialkylation was observed using the 2-imino lactone, while the regioisomeric 3-imino lactone derivative gave monoalkylated products with diastereoselectivities, shown by NMR spectroscopy, to range from 43% d.e. for the methylated product to > 99% d.e. for larger alkyl groups. The expected preference for endo-alkylation is supported by NMR (chemical shift, coupling constant and NOE) data and was confirmed by acidic hydrolysis of the pentylated 3-imino lactone to afford the known acid. Computer modelling, with the software package HYPERCHEM®, was used to explore the conformational properties of the alkylated products and their enolate precursors. Exploratory work on the enantiomeric beneficiation of racemic amino acids, using alkylated imino lactone derivatives, revealed preferential exo-protonation of the enolate intermediates. Asymmetric Baylis-Hillman reactions between a novel camphor-derived acrylic ester and a range of aldehydes afforded the corresponding 2-(hydroxyalkyl)acrylates in up to 59% d.e., the observed stereoselectivities being sensitive to both steric and electronic factors. Attempts to prepare imino lactone derivatives from ketopinic acid, although unsuccessful, led to the isolation of two novel W-(carbobenzyloxy)glycinates, whose structures were established by 1- and 2-D NMR spectroscopy. Attempts to prepare "BINAP" analogues from dibomyl ether's also proved unsuccessful, but the investigation led to the discovery of a third, novel dibomyl ether. , Thesis (PhD) -- Faculty of Science, Chemistry, 1998
- Full Text:
- Date Issued: 1998-04
- Authors: Matjila, Joseph Moemise
- Date: 1998-04
- Subjects: Imino compounds , Alpha-amino acid , Asymmetric synthesis , Camphor , Enantioselective catalysis , Baylis–Hillman reaction
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/191501 , vital:45106
- Description: A viable synthetic route to camphor-derived imino lactones as precursors for the asymmetric synthesis of a-amino acids has been established. Several synthetic strategies have been investigated and the required regioisomeric imino lactones were finally obtained via the step-wise condensation of JV-(carbobenzyloxy)glycine with the a-ketols, 3-exo-hydroxycamphor and 2-exo- hydroxy-3-bomanone. Enolates of the camphor imino lactones, generated using potassium tert- butoxide, were reacted with a range of alkyl halides. Dialkylation was observed using the 2-imino lactone, while the regioisomeric 3-imino lactone derivative gave monoalkylated products with diastereoselectivities, shown by NMR spectroscopy, to range from 43% d.e. for the methylated product to > 99% d.e. for larger alkyl groups. The expected preference for endo-alkylation is supported by NMR (chemical shift, coupling constant and NOE) data and was confirmed by acidic hydrolysis of the pentylated 3-imino lactone to afford the known acid. Computer modelling, with the software package HYPERCHEM®, was used to explore the conformational properties of the alkylated products and their enolate precursors. Exploratory work on the enantiomeric beneficiation of racemic amino acids, using alkylated imino lactone derivatives, revealed preferential exo-protonation of the enolate intermediates. Asymmetric Baylis-Hillman reactions between a novel camphor-derived acrylic ester and a range of aldehydes afforded the corresponding 2-(hydroxyalkyl)acrylates in up to 59% d.e., the observed stereoselectivities being sensitive to both steric and electronic factors. Attempts to prepare imino lactone derivatives from ketopinic acid, although unsuccessful, led to the isolation of two novel W-(carbobenzyloxy)glycinates, whose structures were established by 1- and 2-D NMR spectroscopy. Attempts to prepare "BINAP" analogues from dibomyl ether's also proved unsuccessful, but the investigation led to the discovery of a third, novel dibomyl ether. , Thesis (PhD) -- Faculty of Science, Chemistry, 1998
- Full Text:
- Date Issued: 1998-04
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