This thesis deals with the design of ligands for efficientasymmetric catalysis and studies of the conformation of theligands in the catalytically active complexes. All ligandsdeveloped contain chiral oxazoline heterocycles. The conformations of hydroxy- and methoxy-substitutedpyridinooxazolines and bis(oxazolines) during Pd-catalysedallylic alkylations were investigated using crystallography,2D-NMR techniques and DFT calculations. A stabilising OH-Pdinteraction was discovered which might explain the differencein reactivity between the hydroxy- and methoxy-containingligands. The conformational change in the ligands due to thisinteraction may explain the different selectivities observed inthe catalytic reaction. Polymer-bound pyridinooxazolines and bis(oxazolines) weresynthesised and employed in Pd-catalysed allylic alkylationswith results similar to those of monomeric analogues;enantioselectivities up to 95% were obtained. One polymer-boundligand could be re-used several times after removal of Pd(0).The polymer-bound bis(oxazoline) was also used in Zn-catalysedDiels-Alder reactions, but the heterogenised catalyst gavelower selectivities than a monomeric analogue. A series of chiral dendron-containing pyridinooxazolines andbis(oxazolines) were synthesised and evaluated in Pd-catalysedallylic alkylations. The dendrons did not seem to have anyinfluence on the selectivity and little influence on the yieldwhen introduced in the pyridinooxazoline ligands. In thebis(oxazoline) series lower generation dendrimers had a postiveon the selectivity, but the selectivity and the activitydecreased with increasing generation. Crown ether-containing ligands were investigated inpalladium-catalysed alkylations. No evidence of a possibleinteraction between the metal in the crown ether and thenucleophile was discovered. A new type of catalyst, an oxazoline-containing palladacyclewas found to be very active in oxidations of secondary alcoholsto the corresponding aldehydes or ketones. The reactions wereperformed with air as the re-oxidant. Therefore, this is anenviromentally friendly oxidation method. <b>Keywords:</b>asymmetric catalysis, chiral ligand,oxazolines, conformational study, allylic substitution,polymer-bound ligands, dendritic ligands, crown ether,oxidations, palladacycle.

No description available.

This thesis describes the use of chiral counter-ions for the enantiomeric separation of amines in non-aqueous capillary electrophoresis. The investigations have been concentrated on studies of the influence, of the chiral counter-ion, the solvent, the electrolyte and the analyte, on the enantioselective separation. Modified divalent dipeptides have been introduced in capillary electrophoresis for the separation of amino alcohols and chiral resolution of amines. Association constants for the ion-pair between dipeptide and amino alcohol could be utilized for development of separation systems with higher amino alcohol selectivity. Chiral discrimination (ion-pair formation) between the dipeptides and amines are preferably generated in non-aqueous background electrolytes (BGEs). The amount of triethylamine in the BGE determined the dipeptide charge and a divalent dipeptide promoted higher enantioselectivity than a monovalent dipeptide. An N-terminal-end blocking group and glutamic acid at the C-terminal-end of the dipeptide was important for chiral separation of the amines. Chemometric and univariate methods have been employed for evaluation of suitable solvent compositions in the BGE. An experimental design including a single solvent as well as binary, ternary and quaternary mixtures of polar organic solvents, showed that optimal enantioresolution was obtained with an ethanol:methanol 80:20 mixture in the BGE.  Furthermore, water was found to have an adverse influence on enantioselectivity and no enantioresolution was obtained with BGEs containing more than 30 % water. An alkali metal hydroxide added to the BGE affected the chiral separation by competing ion-pair formation with the selector. The electroosmosis was reduced in order of decreasing alkali metal ion solvated radius and became anodic using K, Rb or Cs in ethanolic BGEs. The correlation between the amino alcohol structure and the enantioselectivity was investigated using chemometrics. The obtained models showed that enantioselectivity for the amino alcohols was promoted by e.g. degree of substitution and substituent size on the nitrogen.

Amino alcohols are valuable bioactive substances and frequently used as chiral catalyst in various asymmetric transformation reactions. In the synthetic route, the asymmetric synthesis of novel chiral N,N-dialkyl substituted chiral 1,4-amino alcohols are performed starting with meso-anhydride 38. Quinine-mediated desymmetrization of the anhydride with methanol afforded (2S,3R)-cis-monoester 39 with a high enantiomeric excess (up to 98% ee). Chemoselective amidation of hemiester with various N,N-dialkyl substituted amines resulted in amido esters and they were subjected to LAH reduction to afford chiral 1,4-amino alcohol ligands. The activities of the chiral ligands, (2S,3R)-43, (2S,3R)-44, (2S,3R)-45, (2S,3R)-46 were tested in various asymmetric transformation reactions, i.e. asymmetric diethylzinc addition and asymmetric Diels-Alder reactions. Keywords: 1,4-Amino alcohols, chiral ligand, asymmetric diethylzinc addition reaction, Diels-Alder reaction

In the first part of this study, four new chiral ligands (FAM) were synthesized and used in catalytic amounts in asymmetric 1,3-dipolar cycloaddition reactions of azomethine ylides. This method leads to the synthesis of chiral pyrrolidines, which are found in the structure of many biologically active natural compounds and drugs. It was found that using 10 mol% of one of these chiral ligands with different dipolarophiles (dimethyl maleate, dimethyl fumarate, methyl acrylate, tert-butyl acrylate, and Nmethylmaleimide), pyrrolidine derivatives could be synthesized in up to 94% yield and 95% ee. In the second part of the study, the catalytic activity of these chiral ligands were tested with titanium in asymmetric alkynylzinc addition reactions to aldehydes. By this method, chiral propargylic alcohols, which are important precursors for the natural products and pharmaceuticals can be synthesized. Using our catalyst, chiral propargylic alcohols were obtained in up to 96% yield and 98% ee. Although, most of the catalyst systems in the literature worked only with aromatic or aliphatic aldehydes and phenylacetylene, the catalyst system developed in this study worked with four different types of aldehydes (aromatic, aliphatic, heteroaromatic and a,b-unsaturated) and two different aliphatic acetylenes very successfully. Additionally, chiral ligand can be recovered in more than 90% yield and reused without losing its activity.

In this study new twelve phosphorus based chiral ligands were synthesized and characterized. Then the catalytic activity of these chiral ligands was tested with Cu(II) and Ag(I) salts in asymmetric 1,3-dipolar cycloaddition reactions of azomethine ylides. This method provides the synthesis of different pyrrolidine derivatives with up to four stereogenic centers. Pyrrolidine derivatives are found in the structure of many biologically active natural compounds and drugs. Therefore the asymmetric synthesis of these compounds is highly important and many groups are involved in this area. As the precursor of the azomethine ylides, N-benzyliden-glycinmethylester, N-(4-methoxy benzyliden)-glycinmethylester, N-(naphthalene-1-ylmethylene)-amino-acetic acid methyl ester, and N-(naphthalen-2-ylmethylene)-amino-acetic acid methyl ester were synthesized and used. As the dipolarophiles, methyl acrylate, dimethyl maleate and N-methyl maleimide were used. Using these imines and dipolarophiles with 6 mol % of one of the P-FAM chiral ligands in the presence of Ag(I) salt, pyrrolidine derivatives were synthesized in up to 95% yield and 89% enantioselectivity. Additionally, chiral ligand was recovered in more than 80% yield and reused without losing its activity.

In this study, resolution of racemic mandelic acid by enyzme enhanced ultrafiltration (EEUF) was studied. In order to develop a methodology, bovine serum albumin (BSA) was used as a model protein for polymer enhanced ultrafiltration (PEUF) experiments and the enzyme S-mandelate dehydrogenase was used for EEUF experiments. To be used for enzyme enhanced ultrafiltration experiments, the gene which is responsible from the production of S-mandelate dehydrogenase was isolated from Pseudomonas putida, expressed in Escherichia coli and the recombinant enzyme was produced. For PEUF experiments, effects of pH and ligand ratio were investigated. Total retention of mandelic acid increased with decrease in pH and total retention of mandelic acid reached to a maximum value of 74.4% at pH 4.3. For EEUF experiments, pH and ligand ratio effect on total retention, enantiomeric excess, enantioselectivity were investigated. Although apoenzyme was tried to be obtained by diafiltration and conversion was tried to be prevented, conversion occured especially at high pH values. To create the apoenzyme effect, three methods were studied. Enzyme conversion was prevented by sodium sulfite inhibition but enzyme did not retain mandelic acid. By oxygen saturation of enzyme, conversion was prevented, binding was achieved but enzyme showed no enantioselectivity. When the enzyme was diafiltrated at pH 10.0, total mandelic acid retention, enantiomeric excess and enantioselectivity reached to 77.2%, 38.9%, 2.27, respectively and the enzyme selectivity was reversed as R-selective.

Among Nature's creation, terpenoids are more versatile and exciting natural products. In a remarkable display of synthetic ingenuity and creativity, nature has endowed terpenes with a bewildering array of carbocyclic frameworks with unusual assemblage of rings and functionalities. This phenomenal structural diversity of terpenes makes them ideal targets for developing and testing new synthetic strategies for efficient articulation of carbocyclic frameworks. The thesis entitled “Enantiospecific approaches to komarovispiranes” describes the utility of the monoterpene α-campholenaldehyde as chiral starting material in the enantiospecific synthesis of a variety of bi- and tricyclic compounds, and enantiospecific first total synthesis of spiro diterpenes komarovispiranes. For convenience the results are described in two different sections, viz., (a) Chiral synthons from α-campholenaldehyde; and (b) Enantiospecific synthesis of a komarovispirane. In the thesis, the compounds are sequentially numbered (bold) and the references are marked sequentially as superscripts and listed in the last section of the thesis. Complete details of the experimental procedures and the spectroscopic data were provided in the experimental section. A brief introduction is provided wherever appropriate to keep the present work in proper perspective. All the spectra included in the thesis were obtained by xeroxing the original NMR spectra. Monoterpenes are widely used as chiral auxiliaries, but their potential as chiral synthons has not been properly exploited. In the present thesis, utility of α-campholenaldehyde, which is readily available from α-pinene in two steps, as chiral synthon has been demonstrated in the enantiospecific synthesis of a few bi- and tricarbocyclic frameworks as well as spiroditerpenes komarovispiranes. To begin with, synthesis of several bi- and tricyclic compounds, namely bicyclo[3.3.0]octan-3-one; bicyclo[3.2.1]octan-2-one; bicyclo[3.2.1]octan-3-one; 3-cyclopentylcyclopentanone; bicyclo[4.3.0]non-3-one; spiro[4.4]non-2-one; tricyclo[6.3.0.02,6]undecan-6-ol; and spiro[4.5]decan-2-one; have been accomplished employing an intramolecular rhodium carbenoid C-H insertion, intramolecular type II carbonyl ene cyclisation, intramolecular acid catalysed diazoketone cyclisation reactions and ring-closing metathesis (RCM) reaction as the key steps. Komarovispirone is a tricyclic spiro diterpene isolated from Dracocephalum komarovi Lipsky, a perennial semishrub available in Uzbekistan and exhibits trypanocidal activity. The novel diterpene containing an unusual carbon framework, cyclohexane spiro fused to bicyclo[4.3.0]nonane, coupled with the potential biological activity have made komarovispirone, and its analogues interesting and challenging synthetic targets. Initially, as a model study, enantiospecific synthesis of a bis-norkomarovispirane was developed employing 7,8,8-trimethylbicyclo[3.3.0]oct-6-en-3-one as the starting material, which was readily available from campholenaldehyde. A Claisen rearrangement and RCM reaction based methodology was developed for the spiroannulation of a cyclohexane ring at the C-3 position of the bicyclo[3.3.0]octan-3-one. For the enantiospecific first total synthesis of komarovispiranes, the AB-trans ring system was generated via ring expansion of 7,8,8-trimethylbicyclo[3.3.0]oct-6-en-3-one employing ozonolytic cleavage followed by an intramolecular aldol condensation reaction of the resultant keto aldehyde. For the generation of the ABC ring system of the komarovispiranes, initially, a Claisen rearrangement and intramolecular type II carbonyl ene reaction based methodology was developed for the spiroannulation of a cyclohexane ring at the C-8 position of the bicyclo[4.3.0]nonan-8-one. Subsequently, an alternate Claisen rearrangement-RCM reaction based methodology was also developed for the spiroannulation, and extended it to the first total synthesis of a komarovispirane.

<p>This thesis deals with the design of ligands for efficientasymmetric catalysis and studies of the conformation of theligands in the catalytically active complexes. All ligandsdeveloped contain chiral oxazoline heterocycles.</p><p>The conformations of hydroxy- and methoxy-substitutedpyridinooxazolines and bis(oxazolines) during Pd-catalysedallylic alkylations were investigated using crystallography,2D-NMR techniques and DFT calculations. A stabilising OH-Pdinteraction was discovered which might explain the differencein reactivity between the hydroxy- and methoxy-containingligands. The conformational change in the ligands due to thisinteraction may explain the different selectivities observed inthe catalytic reaction.</p><p>Polymer-bound pyridinooxazolines and bis(oxazolines) weresynthesised and employed in Pd-catalysed allylic alkylationswith results similar to those of monomeric analogues;enantioselectivities up to 95% were obtained. One polymer-boundligand could be re-used several times after removal of Pd(0).The polymer-bound bis(oxazoline) was also used in Zn-catalysedDiels-Alder reactions, but the heterogenised catalyst gavelower selectivities than a monomeric analogue.</p><p>A series of chiral dendron-containing pyridinooxazolines andbis(oxazolines) were synthesised and evaluated in Pd-catalysedallylic alkylations. The dendrons did not seem to have anyinfluence on the selectivity and little influence on the yieldwhen introduced in the pyridinooxazoline ligands. In thebis(oxazoline) series lower generation dendrimers had a postiveon the selectivity, but the selectivity and the activitydecreased with increasing generation.</p><p>Crown ether-containing ligands were investigated inpalladium-catalysed alkylations. No evidence of a possibleinteraction between the metal in the crown ether and thenucleophile was discovered.</p><p>A new type of catalyst, an oxazoline-containing palladacyclewas found to be very active in oxidations of secondary alcoholsto the corresponding aldehydes or ketones. The reactions wereperformed with air as the re-oxidant. Therefore, this is anenviromentally friendly oxidation method.</p><p><b>Keywords:</b>asymmetric catalysis, chiral ligand,oxazolines, conformational study, allylic substitution,polymer-bound ligands, dendritic ligands, crown ether,oxidations, palladacycle.</p>

No description available.