No description available.

No description available.

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. / Thesis (Ph.D.)-University of KwaZulu-Natal, 2009.

I. Catalytic Conjugate Allylation of Alkylidene Malonates Nucleophilic conjugate addition of allylsilanes and allylstannanes to alkylidene malonates under the action of ytterbium catalysis in the presence of hexafluoro-isopropanol has been developed. Enantioselective conjugate allylation of alkylidene malonates under ytterbium or scandium catalysis using chiral bis(oxazoline) ligands allows access to the conjugate addition products in an enantiomerically-enriched form. Furthermore, elaboration of the allylated substrates via decarboxylation and an oxidative cleavage was demonstrated. II. Catalytic Enantioselective Conjugate Addition of Azaarylacetates and Acetamides to Nitroalkenes An enantioselective nickel-catalysed Michael addition of azaarylacetates and acetamides to nitroalkenes has been developed. A range of azaaryl pronucleophiles were shown to react with a variety of nitroalkenes to generate highly functionalised Michael addition products with impressive diastereo- and enantiocontrol. A possible mechanism for this process is proposed and crystal structures of the addition products have also been attained, allowing determination of the absolute stereochemistry. Elaboration and further functionalisation of these products was also possible under a range of conditions.

Diastereoselective control of glycosylation still remains a difficult task. Therefore, new glycosylation methods using asymmetric catalysis were developed to control the diastereoselectivity. Two systems were developed and each focused on a separate type of glycosyl donor. In the first system, glycosyl halides were subjected to reaction conditions inspired by Hamilton et al., who effectively had controlled the substitution of a racemic chloroamine by an alcohol. Asymmetric control of glycosylation was achieved through this adapted catalytic system. Both enantiomers of the catalyst ((R) and (S) TRIP) generally displayed b-selectivity with tertiary butyl methyl ether (TBME) as the solvent allowing almost exclusive formation of the β-anomer. However, low and inconsistent yields were obtained. The second system proposed the use of the same phosphoric acid catalyst (TRIP) to catalyse the glycosylation of glycals. However, this was ineffective as the catalyst was not a strong enough Brønsted acid. These studies then led to the development of two new chiral catalysts which then promoted the glycosylation of glycals, along with the formation of an undesired side product. Attempts were made to reduce the formation of the side product but unfortunately this proved unsuccessful. The diastereoselective outcome displayed between the different catalysts in separate trials was negligible, but the principles developed in this study should lead to the further development of new chiral catalysts for the glycosylation of glycals.

The success of homogeneous asymmetric catalysis has been attributed to the structure and stereochemistry of the coordinated ligand(s). The most effective ligands are C₂-symmetrical bisphosphines containing either a rigid chiral backbone linking two PPh₂ units or a bisphosphine, DIPAMP containing two chiral phosphine units linked by an achiral backbone. The synthesis of P-chiral ligands of this type has been severely hindered by the lack of a general synthetic route allowing the incorporation of phosphorus chirality without the need for separation of diastereomeric precursors or resolution of intermediate enantiomers. The objective of this work was to develop a general synthetic route to homochiral bulky arylphosphines with substantial flexibility in the groups at phosphorus and extend the approach to new P-chiral bisphosphines. In one approach, diastereomerically pure (2R, 4S, 5R)-2,5-diphenyl-3,4-dimethyl-1,3,2-oxazaphospholidine was prepared directly from PhPCl₂ using l-ephedrine as a chiral auxiliary. Stereospecific oxidation using Bu^tOOH gave the corresponding P-oxide which was shown to have R-stereochemistry at phosphorus by single-crystal X-ray diffraction studies. The compound reacted regiospecifically with ortho-anisylmagnesium bromide to afford the product formed by P-O bond cleavage with >96% d.e. and with retention of configuration at phosphorus as demonstrated by single-crystal X-ray diffraction studies. The l-ephedrine residue was replaced by O-methyl under acid-catalysis with inversion of configuration and with >95% e.e., the reaction was monitored by ¹H n.m.r. spectroscopy which gave t_1/2 of ca. 30 min. Attempts to incorporate para-fluorophenol using similar conditions led to the isolation of the pyrophosphinate in low yield. The OMe residue in the methyl (ortho-anisyl)phenylphosphinate was readily displaced by aliphatic Grignard reagents giving the corresponding phosphine oxides with inversion of configuration and with >95% e.e. Displacement of methoxy using aryl magnesium bromides showed similar enantioselectivity but in lower chemical yield, however the corresponding arylmagnesium chlorides were more efficient. In a second approach, diastereomerically pure (2R, 4S, 5R)-2-chloro-3,4-dimethyl-5-phenyl-1,3,2-oxazaphospholidine was prepared from PCl₃ and l-ephedrine. The compound underwent diastereoselective P-C1 cleavage with aryl Grignard and aryllithium reagents with net retention of configuration at phosphorus and with 90% d.e. Oxidation of the ortho-anisyl derivative afforded (2R, 4S, 5R)-2-(ortho-anisyl)-3,4-dimethyl-5-phenyl-1,3,2-oxazaphospholidine-2-oxide which was subsequently reacted with a range of bulky aryl Grignard reagents to afford the corresponding biarylphosphinamides with retention of configuration at phosphorus. Subsequent acid-catalysed methanolysis and displacement of the methoxy residue with PhMgCl afforded a range of bulky arylphosphine oxides with defined configuration at phosphorus with >95% e.e. as determined by ¹H n.m.r. methods. (S)-ortho-anisyl (meta-anisyl)phenylphosphine oxide underwent regiospecific ortho-lithiation on the meta-anisyl ring which on quenching with D₂O afforded the corresponding 2-deuteride in 80% yield. The 2-iodo analogue was also prepared although in low chemical purity and is a key precursor to new axially dissymmetric bisphosphines containing chiral phosphorus centres. Other approaches to P-chiral ferrocenyl ligands and biaryl ligands are also described and modifications for further development are implicated. An X-ray crystallographic study of six aryl-oxazaphospholidines is also presented and demonstrates the influence of the substituents at phosphorus in determining the conformation of the 1,3,2-oxazaphospholidine ring. A comparison with solution ¹H n.m.r. data showed, in some cases, good correlation between the P-O-C-H dihedral angle and the corresponding solid state torsion angle.

No description available.

This thesis describes three types of reactions that were carried out using iridium catalysts. The first type is the iridium-catalyzed asymmetric hydrogenation of olefins. In paper I, the preparation of a new type of bicyclic thiazole-phosphine based iridium complex was described. The new catalysts have displayed high activity and enantioselectivity in the asymmetric hydrogenation of unfunctionalized olefins. Papers II and III focus on the expansion of the substrate scope for the iridium catalyzed asymmetric hydrogenation in which a number of heterocyclic olefins were evaluated. In paper IV, the enantioselective asymmetric hydrogenation of α, β-unsaturated esters was described. The chiral products bearing tertiary stereogenic centers obtained by hydrogenation have great synthetic value and have been used in the synthesis of pharmaceuticals as well as in the total synthesis of natural products. The second type is the asymmetric isomerization of allylic alcohols. In paper V, both cis and trans primary allylic alcohols were isomerized to the corresponding β-chiral aldehydes in high enantioselectivities by an N,P-chelating iridium complex. The third type is the selective mono-N-alkylation of amines with alcohols. In paper VI, a phosphine/NHC based iridium catalyst was synthesized and applied in the alkylation of amines. It is the first time that this type of transformation is carried out at room temperature.

Thesis (M.S.)--West Virginia University, 2008. / Title from document title page. Document formatted into pages; contains vi, 78 p. : ill. Includes abstract. Includes bibliographical references (p. 37-38).

Thesis (Ph.D.) - University of St Andrews, May 2008.