The first stable “free” N-heterocyclic carbene (NHC) was isolated in 1991, since then many classes of NHCs were synthesized and isolated. N-heterocyclic carbene ligands have become a common ligand in the synthesis of metal complexes, due to their strong σ-donation with poor πeptor ability. Among all the NHC metal complexes, Hollis group was interested in exploring -NHC pincer complexes. In 2005, Hollis and co-workers synthesized and isolated first achiral -NHC zirconium pincer amido complex and studied its catalytic ability to perform intramolecular hydroamination of aminoalkenes. Later, Hollis group designed and developed new NHCs with a saturated chiral backbone, and used these new ligands to generate a new series of metal complexes. This dissertation is focused on the design, synthesis and characterization of several chiral bi-dentate NHC ligands with varying substituents on the backbone. These NHC ligands were used to synthesize several chiral mono, bis and tris amido -NHC zirconium pincer complexes. Further, transmetallation to cobalt complexes were achieved. Intramolecular hydroamination was measured for several chiral bis and tris amido -NHC pincer zirconium catalysts. Variants of these catalytic systems were generated with differing steric hinderance and electronic structure. The enantioselectivity of these novel new molecules were studied.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

<p> The catalytic asymmetric transformation of carbonyl compounds via iminium and enamine intermediates using chiral amines as organocatalyst has grown remarkably over last decade. Various "metal-free" reactions including aldol, Mannich, Michael, alkylation and Knoevenagel types have now been reported efficiently using simple amino acids as the sole organocatalysts. Amongst these, proline has proven to be particularly useful as a general catalyst in such catalytic asymmetric syntheses due to its unique properties. Nonetheless, proline suffers inherent fundamental disadvantages as an organocatalyst in terms of its solubility in organic media, limiting reactions to polar aprotic solvents such as DMF or DMSO. We have been interested in the synthesis of derivatives of proline incorporating functional groups that would render the chiral secondary amine fully soluble in organic solvents such as THF or dichloromethane and others that could be employed in aqueous media. The synthesis of these catalysts and their application towards the asymmetric synthesis will be presented.</p> <p> The thesis also describes isolation and identification of natural products and synthesis of their semi-stabilised derivatives. Sakuranetin and dihydrowagonine were isolated from Prunus avium plant parts, menisadurilide was isolated from Dicentra spectabilis extracts while narciclasine was isolated from Narcissus pseudonarcissus plant parts. Semi-synthetic derivative, trans-dihydronarciclasine was prepared from natural product narciclasine. Both the derivatives were subjected to antifungal and human cytochrome inhibition activity and their correlation is explained. The Amaryllidaceae family alkaloids and their semi-synthetic derivatives were subjected to biological testing and an important structural property is correlated to their activities.</p> / Thesis / Master of Science (MSc)

<p> A series of chiral transition metal clusters of the type MCo2(CO)6C-CO2R, where M = Co(CO)3, (C5H5)Mo(CO)2, (i-Pr-C5H4)Mo(CO)2 or (indenyl)Mo(CO)2 and R =menthyl or exo-bornyl have been synthesized and characterized using FAB mass spectrometry and high field NMR techniques. The isopropyl Cp and the indenyl ligands served as NMR probes to detect the chirality created by the incorporation of the terpenoidal capping group.</p> <p> The tricobalt clusters were treated with the bidentate ligands arphos, Ph2AsCH2CH2PPh2 and diphos, Ph2PCH2CH2PPh2. Treatment with arphos yields a pair of diastereomers which are interconverted via the migration of the Ph2As terminus of the arphos ligand from one cobalt vertex to another. This fluxionality was monitored by variable-temperature 31P NMR spectroscopy. The diphos cluster is not a fluxional molecule. However, the Co(CO)2P vertices are diastereotopic and give two signals in the 31P NMR. Thus, diphos serves as a convenient probe for chirality. </p> <p> In the case where M = Co(CO)3 , the two remaining cobalt vertices are diatereotopic and are, in principle, not equally susceptible to attack by an incoming ligand. To test for chiral discrimination, these molecules have been treated with several different phosphines. If the reaction were to proceed with any degree of selectivity, the 31P NMR spectrum ought to show resonances of unequal intensity. Such results have been obtained when a bulky phosphine, such as tricyclohexylphosphine, has been employed.</p> / Thesis / Master of Science (MSc)

Various innovative separation methods in chromatography have been proposed. The interaction of the 4-t-butylphenyl group with b-cyclodextrin is well-known; compounds tagged with the 4-t-butylphenyl group are separated from untagged compounds using b-cyclodextrin column. In this study, increasing the chain length of tagged molecules does not increase the retention time but depends on other functional groups present, while increasing the number of tags in a molecule increases retention time. The t-butyl group was also compared to adamantyl and lithocholic acid tags. In-house b-cyclodextrin columns were synthesized to observe the effect of the linkage of the cyclodextrin molecule to the support. Furthermore, tagged products could be separated from the starting materials using in-house columns employing flash b-cyclodextrin. Supported room temperature ionic liquids (SILs/MSILs) were explored for the extraction of polyunsaturated triacylglycerols (PUTAGs).Various room temperature ionic liquids (RTILs) with silver salts were tested for extraction effectiveness.The most hydrophobic RTIL [Hmim][PF6] in this study, with dissolved AgBF4 proved to be the best combination for effective extraction. RTILs supported on silica gel and mesoporous SBA-15 reacted with silver salts (psorbents) were synthesized and characterized. The later support revealed a conserved mesopore structure by SEM, TEM, SAXS and N2 isotherms. Trilinolenin (tri-18:3) quantification was explored by conversion to polyunsaturated fatty acid alcohols and methyl esters, Proton NMR spectroscopy and by non-aqueous reverse phase (NARP)-HPLC with evaporative light scattering detector (ELSD). Tri-18:3 and its free fatty acid (FFA-18:3) were extracted selectively and quantified using a two-step methodology. The extraction of a-tocopherol with RTILS modified with organic anions was also successfully demonstrated. Finally, studies of chiral stationary phases with on-resin cyclic oligoprolines were demonstrated. Cross linking of linear oligoprolines was shown to disrupt the poly-proline helix (II) thus leading to lower number of analytes resolved. On-resin cyclic oligoproline synthesis was successful for penta- and tetraproline but failed for the triproline. PyBOP/HOBt/DIPEA was employed for effective cyclization. The on-resin cyclic oligoproline CSP showed a lower number of resolved analytes, implying the importance of the poly-proline helix for chiral selectivity. The innovative separations in this study serve as starting points for developing mature separation methods.

No description available.

Yes / A series of novel nopyl-derived chiral phosphonium ionic liquids have been successfully synthesised and characterised. Analysis of each novel ionic liquid was conducted in order to confirm structure, purity and thermal stability.

Yes / Mandelic acids are prototypic chiral molecules where the sensitivity of crystallized forms (enantiopure/racemic compound/polymorphs) to both conditions and substituents provides a new insight into the factors that may allow chiral separation by crystallization. The determination of a significant number of single crystal structures allows the analysis of 13 enantiopure and 30 racemic crystal structures of 21 (F/Cl/Br/CH3/CH3O) substituted mandelic acid derivatives. There are some common phenyl packing motifs between some groups of racemic and enantiopure structures, although they show very different hydrogen-bonding motifs. The computed crystal energy landscape of 3-chloromandelic acid, which has at least two enantiopure and three racemic crystal polymorphs, reveals that there are many more possible structures, some of which are predicted to be thermodynamically more favorable as well as slightly denser than the known forms. Simulations of mandelic acid dimers in isolation, water, and toluene do not differentiate between racemic and enantiopure dimers and also suggest that the phenyl ring interactions play a major role in the crystallization mechanism. The observed crystallization behavior of mandelic acids does not correspond to any simple “crystal engineering rules” as there is a range of thermodynamically feasible structures with no distinction between the enantiopure and racemic forms. Nucleation and crystallization appear to be determined by the kinetics of crystal growth with a statistical bias, but the diversity of the mandelic acid crystallization behavior demonstrates that the factors that influence the kinetics of crystal nucleation and growth are not yet adequately understood. / EPSRC, Max Planck Society for the Advancement of Sciences, UCL-MPS Impact Ph.D. Fellowship, EU COST Action

L'oxazolidine trifluorométhylée (trans-Fox) dérivée du (R)-phénylglycinol a été préparée sous forme diastéréoisomériquement pure par résolution dynamique induite par la cristallisation d'un mélange d'oxazolidines cis et trans.La trans-Fox a été utilisée avec succès comme auxiliaire chiral pour des réactions d'hydroxylation par l'oxygène moléculaire et de fluoration électrophile d'énolates d'amide ainsi qu'en réarrangement sigmatropique [2,3] d'amines allyliques. Après clivage, des composés énantiomériquement purs d'une grande importance synthétique sont obtenus.Une voie d'accès à des pyrrolydines trifluorométhylées chirales a été mise au point à partir de la trans-Fox. La trans 2-phenyl-5-trifluoromethylpyrrolidine a été utilisée comme auxiliaire chiral pour des réactions d'alkylation asymétriques. / The trifluoromethylated oxazolidine (trans-Fox) derived from (R)-phenylglycinol was prepared as a single diastereoisomer by a cristallisation induced dynamic resolution of a mixture of cis and trans oxazolidines.The trans-Fox was used with success as a chiral auxiliary for hydroxylation by oxygen and electrophilic fluorination of amide enolates reactions and [2,3] sigmatropic rearrangements of allylic amines. After deprotection, very synthetically useful enantiomerically pure compounds were obtained.An acces to chiral trifluoromethylated pyrrolidines was developped starting from trans-Fox. The trans 2-phenyl-5-trifluoromethylpyrrolidine was used as a chiral auxiliary for asymmetric alkylation reactions.

This thesis deals with the preparation and use of chiralbispyridylamides as ligands in metal-catalyzed asymmetricreactions. The compounds were prepared by amide formation usingdifferent coupling reagents. Bispyridylamides havingsubstituents in the 4- or 6- positions of the pyridine ringswere prepared by functional group interconversion of the 4- or6- halopyridine derivatives. These synthetic approaches provedto be useful for various types of chiral backbones. Pseudo C2-symmetric bispyridylamides were also synthesizedby means of stepwise amide formation. The compounds were used as ligands in themicrowave-accelerated Mocatalyzed asymmetric allylic alkylationreaction. Ligands having ð-donating substituents in the4-positions of the pyridine rings gave rise to products withhigher branched to linear ratio. The catalytic reaction, whichproved to be rather general for allylic carbonates with anaromatic substituent, was used as the key step in thepreparation of (R)-baclofen. The Mo-bispyridylamide catalystprecursor was studied by NMR spectroscopy. Bispyridylamide complexes of metal alkoxides were alsoevaluated in the asymmetric addition of cyanide to aldehydesand the metal complexes involved were studied by NMRspectroscopy and X-ray crystallography. Chiral diamines wereused as additives to study the ring opening of cyclohexeneoxide with azide, catalyzed by Zr(IV)-bispyridylamidecomplexes. Various bispyridylamides were attached to solid supports oforganic or inorganic nature. The solid-supported ligands wereused in Mo-catalyzed asymmetric allylic alkylation reactionsand in the asymmetric addition of cyanide to benzaldehyde. Keywords:asymmetric catalysis, chiral ligand, pyridine,amide, allylic alkylation, enantioselective, cyanation,ring-opening, chiral Lewis acid.