In this thesis, we have investigated the coupling of methane with olefins, such as ethylene and propylene using silica-supported nickel and sulphate-promoted zirconia-silica catalysts. Control experiments over hydrogen-reduced Ni/SiO$\sb2$ in which propylene was co-fed with helium rather than with methane resulted in increased propylene conversions and in an increase of the yields of propane, C$\sb2$'s and C$\sb4$'s. It was concluded that the production of C$\sb4$'s was due to homologation or metathesis reactions, rather than to methane coupling. Variation of the temperature of the methane preactivation treatment from 350$\sp\circ$C to 600$\sp\circ$C revealed an increased CH$\sb4$ conversion from approximately 1% at 350$\sp\circ$C to 60% at 600$\sp\circ$C. Subsequent reaction of $\rm C\sb3H\sb6/CH\sb4$ mixtures over these catalysts at 350$\sp\circ$C revealed that there was virtually no activity over the former catalyst and very little over the latter. However, catalysts activated between 400$\sp\circ$C and 500$\sp\circ$C showed very similar activities. Experiments in which helium was co-fed with propylene rather than methane over CH$\sb4$-preactivated catalysts suggested that the same processes were responsible for C$\sb4$ production over CH$\sb4$-reduced NiO/SiO$\sb2$ and hydrogen-reduced NiO/SiO$\sb2$ i.e. propylene homologation and/or metathesis. Dissociatively adsorbed methane only served to block metal sites at which reactions could otherwise occur. Zirconia-silica, like many binary oxide mixtures, possesses enhanced surface acidity relative to its parent components. TPD experiments using NH$\sb3$ found that samples of 5, 10, and 20 wt.% ZrO$\sb2$/SiO$\sb2$, previously activated by evacuation at 450$\sp\circ$C, contained a similar amount of surface acid sites, 260 $\mu$mole/g sample. XRD analysis revealed no peaks due to crystalline phases following calcination at 450$\sp\circ$C, suggesting that these materials were amorphous, even with zirconia loadings as high as 20 wt.%. Infrared analysis of 10 wt.% ZrO$\sb2$/SiO$\sb2$ with sulphate loadings ranging from 100 to 1000 $\mu$mole/g revealed that the nature of the surface sulphate species was dependent on the temperature of activation. IR analysis using NH$\sb4$ as a probe revealed that both Lewis and Bronsted acid sites existed after 500$\sp\circ$C activation. The amount of each type of acid site appeared to increase with increased sulphate loading. The acidity of 10 wt.% ZrO$\sb2$/SiO$\sb2$ with various loadings of sulphate was measured by gravimetric ammonia adsorption following evacuation at various temperatures. The amounts of irreversibly adsorbed ammonia were found to increase with increased sulphate loading at 25, 100, and 200$\sp\circ$C. Attempts to measure the amount of irreversible adsorption at temperatures greater than 200$\sp\circ$C were hampered by weight loss due to sulphate. Thus, precise measurement of the number of acid sites at high temperature was not possible. Sulphate-promoted ZrO$\sb2$/SiO$\sb2$, previously activated by evacuation at 500$\sp\circ$C, was tested as a catalyst for the coupling of methane and ethylene (or propylene) in a fixed-bed reactor at atmospheric pressure and at temperatures ranging from 225 to 275$\sp\circ$C. All experiments were hampered by rapid deactivation of the catalyst (within 35 minutes on stream) due to oligomerization. Only minute quantities of propane were detected. Reactions of methane alone showed that it also interacted strongly with the catalyst, leading to deactivation. (Abstract shortened by UMI.)

The preparation of chiral amino alcohols which can be used in the asymmetric reduction of acetophenone is described. These amino alcohols were complexed with lithium aluminum hydride (LAH) and achiral agents in various ratios and once treated with acetophenone, afforded l-phenylethanol in poor to moderate optical yields (20%-70%). These chiral molecules were grafted to 1% crosslinked polystyrene and the polymeric hydride complexes yielded l-phenylethanol in lower optical yield than the model compounds. A detailed study of this behavior using l-ephedrine as the chiral auxiliary allowed us to conclude that site interactions as well as site accessibility were responsible for a decrease in the optical yield of the alcohol when the polymer-supported reagent was used in the reduction of the ketone. This polymer behavior is referred to as the "polymer effect". By making use of polymers with a low degree of functionalization, it was nonetheless possible to obtain optical yields comparable to that of the model molecules. Some amino alcohols were also tested as complexes of diborane and similar optical yields to those of the aluminum hydride complexes were obtained. In order to study the limitation of polymer aluminum complexes vs. the borane complexes, we attempted to prepare polymer-supported 83 and 84. Because of the lability of the benzyl ether bond, the desired polymers were not obtained in sufficiently high yield to allow their use in the reduction of acetophenone.

No description available.

Alkyl radicals, generated with tributyltin hydride from their haloprecursors, are trapped efficiently by carbon monoxide under pressure, and the resulting acyl radicals undergo rapid cyclization onto N,N-diphenylhydrazones to yield alpha-hydrazinocyclopentanones. Selective reduction of the resulting ketones provided the corresponding cis- or trans-beta-hydrazinoalcohols, such as 282a--283b. A novel rearrangement was uncovered when the corresponding alpha-carbonyl hydrazine was treated with Lewis acids to afford product 292. Attempted carbonylation of aminyl radicals failed to provide the expected products. Tandem radical reactions were employed for the synthesis of the bicyclic ring system 359. The monocyclized products 362 and 363 were also formed. Attempted synthesis of tropane analogs via tandem radical reactions resulted only in the formation of the 7-membered ring products, such as 406. The level of asymmetric induction in radical carbocyclizations mediated by the presence of hydrazone chiral auxiliaries, such as 417 and 418 was examined.* *Please refer to dissertation for diagrams.

This thesis describes a study of the hydrogenation of different functional groups in the presence of clays or metals anchored on clays as catalysts. The thesis also describes the selective aerobic oxidation of sulfides to sulfoxides using a palladium based catalyst. Chapters 2 and 3 detail work on the hydrogenation processes. Ruthenium clays were prepared using montmorillonite-phosphine or montmorillonite-bipyridine and RuCl3·H2O. The clays obtained were found to be effective catalysts for the reduction of unsaturated esters, epoxides, sulfones and phosphonates. It was shown that Ru-phosphine clay is an efficient catalyst for reduction of the alpha-carbonyl group of alpha-ketoesters and alpha-ketoamides, and the alpha-imine group of alpha-iminoesters and alpha-iminoketones. The reductive amination of alpha-ketoesters with amines, catalyzed by ruthenium clay, was studied. The diastereoselectivity of the reactions was studied using chiral amines. Modification of the clay structure using organic ligands and/or metals was also investigated. The reduction of aliphatic and aromatic ketones by hydrogen transfer was studied. The reaction was catalyzed by sodium montmorillonite and took place under basic conditions (0.06 M KOH in isopropanol). The cis /trans selectivity of the process was also examined. The last chapter (Chapter 4) describes the selective oxidation of sulfides to sulfoxides. The palladium complex [Pd(PBut2H)(mu-PBu t2)]2, on exposure to oxygen in tetrahydrofuran, generates an active catalytic system for this reaction. The presence of other functional groups (amide, carboxyl) does not interfere with the oxidation process at sulfur. It was shown that this process is stereospecific in the case of (+)-biotin-sulfoxide 4-nitrophenyl ester.

Glycomimetics of alpha-D-mannose were synthesized by derivatizing it at the 1-, 2-, and 6-positions. The synthesis of a series of known aryl alpha-D-mannopyranosides and novel aryl thio-alpha-D-mannopyranosides using Lewis acid catalysis is described. The method affords the desired products in very good yields (61--76%). Synthesis of the corresponding, novel arylsulfinyl alpha-D-mannopyranosides and arylsulfonyl alpha-D-mannopyranosides by conventional mCPBA oxidation is also described. The inhibitory effect by the C-1 modified compounds mentioned above on the binding of concanavalin A to yeast mannan was evaluated by ELLA and is reported. Aryl thio-alpha-D-mannopyranosides proved to be better inhibitors than the analogous aryl alpha-D-mannopyranosides. Arylsulfinyl alpha-D-mannopyranosides and arylsulfonyl alpha-D-mannopyranosides are better inhibitors than the corresponding aryl alpha-D-mannopyranosides but poorer inhibitors than the corresponding sulfides, except for p-methoxyphenylsulfonyl 1-thio-alpha-D-mannopyranoside which proved to be the most potent inhibitor of all the above tested compounds. Derivatization of methyl alpha-D-mannopyranoside to methyl 6-amino-6-deoxy-alpha-D-mannopyranoside, methyl 2-O-alkyl-alpha-D-mannopyranosides (alkyl = Me and Bn) and methyl 6-amino-2-O-alkyl-6-deoxy-alpha-D-mannopyranosides (alkyl = Et and Bn) is also described. The inhibitory effect of the first and latter series on the binding of Concanavalin A to yeast mannan was evaluated by ELLA and is reported. Modification of alpha-D-mannose at the 2- and 6-positions decreased the inhibitory effect of the binding of Concanavalin A to yeast mannan.

This thesis consists of four separate chapters. The first three chapters contain a common theme; the diastereoselective synthesis of medicinally relevant compounds using Dynamic Kinetic Resolution (DKR). Unfortunately, in chapter three DKR could not be applied to our desired target, and an alternate route was found. This chemistry allowed for the preparation of two novel classes of bis-indole compounds. Chapter four is unrelated to the first three chapters and describes the synthesis of two tricyclic chiral ligand precursors, using known ring annulation techniques. Chapter One. DKR was applied to the preparation of the core structures of several Angiotensin-converting Enzyme (ACE) inhibitors. High levels of diastereoselectivity were observed in the DKR of [ R]-pantolactone 2-iodo-4-phenylbutanoate with benyl and dibenzylamine, several chiral alpha-amino esters, and [S]-2-aminocaprolactam. The benzolactam core of benazepril was prepared by the DKR of [R]-pantolactone 2-iodo-4-(2-nitrophenyl)butanoate with benzylamine, and reductive cyclization of the resultant DKR product. Chapter Two. The treatment of alpha-halo [ R]-pantolactone esters with various diamines resulted in the formation of optically active 6 membered heterocycles, via DKR mediated displacement of the halide followed by transamidation. Alternately, this reaction yielded diastereomerically enriched bis-alpha-amino esters when the chain length between the amines was greater than 3 carbon atoms. Similarly, alpha-halo [R]-pantolactone acrylates provided 6 membered heterocyclic esters, via a 1,4-Michael addition of one amine to the acrylate, followed by DKR mediated halide displacement by the second amine. Moderate to high levels of diastereoselectivity were observed in these reactions. Chapter Three. beta,beta-Disubstituted and beta-monosubstituted glyoxylate esters reacted with substituted indoles and SnCl4, to provide highly substituted tryptol derivatives in 45 to 70% yield. Conversion of these trytols to the corresponding azides was facilitated by the Mitsunobu reaction, however, it proved difficult to reduce these azides to the corresponding tryptophan derivatives. Ringing opening reaction using ZnI2 as the Lewis acid provided access to alpha,alpha-bis(indolyl) esters. Modifications to this chemistry provided access to alpha,beta- bis(indolyl) esters. Chapter Four. 4,5-Benz-1-indene was prepared regioselectively, in 45--50% yield, after 5 steps, via a modified ring annulation/dehydration process. This new synthetic strategy dramatically increased the overall yield while simplifying the synthetic manipulations required for its preparation. A similar procedure was used in the preparation of a new ligand precursor 8,9,10,11-tetrahydro-4,5-benz(o)indene, in 22% overall yield, after 7 steps.

The preparation of enantiomerically enriched bi- and tricyclic heterocycles via a dynamic kinetic resolution protocol is discussed. This methodology was applied to the reaction of o-bromo-alpha-iodo alkyl [R]-pantolactone esters with a number of bifunctional nucleophiles such as, 1,2-phenylenediamine, which resulted in the formation of bicyclic piperazines. Several other nucleophiles such as 2-aminophenols, also formed the expected heterocycles, but aliphatic 1,2-diamines tended to give elimination rather than displacement products, with the above dihalo esters. The preparation of these heterocycles in a simple three step sequence, starting from commercially available o-bromo alkyl acids is detailed. Attempts were made to prepare benzocyclobutenones and benzocyclobutenols via halogen-metal exchange and subsequent cyclization in o-halobenzyl cyanide. Finally, the reaction of amide, ester and ketone enolates with a benzyne species generated via reaction of halobenzenes with lithium 2,2,6,6-tetramethylpiperidide at room temperature or below is also discussed. The reaction of amide and ester enolates with benzynes has not been previously discussed in the literature. Surprisingly, reaction of ester or amide enolates with benzyne in the presence of excess iodobenzene afforded substituted iodobenzenes as the major reaction product. These products were obtained by reaction of the enolates with benzynes followed by transfer of iodine from iodobenzene. The results represent the first example in which iodobenzene acts as a positive source of halogen.

An enantioselective approach via an intramolecular Diels-Alder reaction to the total synthesis of podophyllotoxin, an antimitotic lignan, is described. The two requisite synthons, an o-quinodimethane precursor, and a chiral tether/dienophile derived from tartrate, were efficiently synthesized, but all attempts at effecting the convergent etherification step failed, likely due to a lack of nucleophilicity of the tartrate-derived primary alcohol. Very reproducible synthetic sequences were developed for the synthesis of a number of different chiral potential tether/dienophile molecules based on tartrate, but connection of these molecules to the diene precursor was never successful. Also described is some investigative work into the synthesis and use in synthesis of phosphonates as (Z)-selective Horner-Wadsworth-Emmons olefination reagents. An efficient synthesis of alkyl diphenyl phosphites and the success of subsequent Arbuzov reactions of these phosphites with halides has led to the synthesis of a number of new olefination reagents, for which evaluation of the (Z)-selectivity is ongoing.

The importance of cell surface carbohydrates in biological processes has led to remarkable progress in carbohydrate synthesis and glycobiology. However, efficient protocols for building oligosaccharides from monosaccharide components are still the major challenges in the field of carbohydrate synthesis. On the other hand, individual carbohydrate-protein interactions are characterized by low affinities. This drawback can be overcome by using the "multivalent or cluster effect". Therefore, the chemical synthesis of oligosaccharides and multivalent glycoconjugates is presented herein. A very simple and efficient synthetic route towards N-acetyllactosamine derivatives was developed. This strategy has used "lightly protected" acceptors, 6-O-tert-butyldiphenylsilyl protected N-acetylglucosamine derivatives, to reduce tedious multiple protection and deprotection steps. Most importantly, these 6-O-tert-butyldiphenylsilyl protected N-acetylglucosamine acceptors allow the regiospecific introduction of a galactosyl moiety. In addition, this method constitutes a highly practical synthesis of Lewis X trisaccharide. The "active-latent" glycosylation strategy made it possible to manipulate the reactivity of both glycosyl donors and acceptors by means of changing the electron density of the aryl substituents at the anomeric center. This strategy provides a facile approach toward the synthesis of complex oligosaccharides such as Lewis X pentasaccharide in a highly convergent manner. The facile regio- and alpha-stereoselective glycosidation of Neu5Ac with several glycosyl acceptors was achieved using a thiophilic promoter (NIS/TfOH) in acetonitrile under kinetically controlled conditions. Under such conditions, the desired sialyl-alpha-(2→3)- and sialyl-alpha-(2→6)-sugar derivatives were obtained in good yields. The syntheses of sialyl alpha-(2→6) thioglycosides were also achieved in situ using diethylamine in chemoselective de-S-acetylation of thioacetate sialic acid derivative. These sialoside derivatives with their azido or p-nitrothiophenyl aglycone can be simply transformed into various neoglycoconjugates using well-established strategy. Glycoclusters with various valencies were synthesized using transition metal-catalyzed reactions. Grubbs' ruthenium benzylidene catalyst had been successfully applied in olefin metathesis reactions from alkenyl sialic acid derivatives. The reactions afforded divalent sialoside derivatives in reasonable yields under mild reaction conditions. Using copper (I)-catalyzed Glaser reaction and palladium-catalyzed Sonogashira reaction, divalent 'rod-like' glycoclusters; were prepared from terminal alkynes such as 2-propynyl thioglycosides in excellent yields. Such strategies also allowed 2-propynyl O-and S-sialic acid derivatives to form dimers, trimers and tetramers, respectively. Divalent sialosides scaffolded on p-tert-butylcalix[4]arene were prepared using an isothiocyanate conjugation strategy. Following the same strategy, a GM3 isothiocyanate derivative was coupled with multivalent amines based on gamma-resorcylic acid- or gallic acid-cores to give multivalent GM3 ligands in good yields. This strategy was extended to synthesize starburstRTM PAMAM-based glycodendrimers. PAMAM cores with generation G0 to G1 were conjugated with the GM3 isothiocyanate derivative to give hypervalent thiourea derivatives containing four and eight GM3 trisaccharide residues. Lactosamine- and GM3-containing glycopolymers were successfully prepared by incorporating the corresponding amine-terminated glycosides into pre-formed active poly(N-oxysuccinimidyl acrylate). The grafting polymerization reactions are carried out under mild conditions and afford fair to good yields.