No description available.

Meso 1,9-diketones (six to seven stereocenters)are readily obtained by stepwise or simultaneous two-directional aldol reactions of tetrahydro-4H-thiopyran-4-one with a thiopyran-derived aldehyde. Enantioselective enolizations of these diketones with the lithium amide from (R,R)-bis(1-phenylethyl)amine occur with simultaneous kinetic resolution to give the mono-TMS enol ethers in >90% yields based on recovered starting material (BORSM) and >90% ee. The developed methodology was applied in synthetic studies towards the asymmetric synthesis of denticulatin A.

Meso 1,9-diketones (six to seven stereocenters)are readily obtained by stepwise or simultaneous two-directional aldol reactions of tetrahydro-4H-thiopyran-4-one with a thiopyran-derived aldehyde. Enantioselective enolizations of these diketones with the lithium amide from (R,R)-bis(1-phenylethyl)amine occur with simultaneous kinetic resolution to give the mono-TMS enol ethers in >90% yields based on recovered starting material (BORSM) and >90% ee. The developed methodology was applied in synthetic studies towards the asymmetric synthesis of denticulatin A.

No description available.

The accomplishment of the γ-alkylation reaction from β-keto esters of tropinone and the enantioselective aziridine formation from nortropinone is first reported. This opened two new paths to develop tropinone enolate chemistry. One is indirect α-alkylation of tropinone, another is the nucleophilic attack from α-C enolate to the nitrogen atom.<p>Seven interesting chiral amines have been synthesized and applied into the enolate chemistry of two interesting precursors of synthesis of natural products: 1,4- cyclohexanedione monoethylene ketal and tropinone.<p>The aldol reaction between the lithium enolate of 1,4-cyclohexanedione monoethylene ketal and benzaldehyde demonstrated the high diastereoselectivity (up to 98% de) and the moderate to high enantioselectivity (up to 75% ee) induced by those chiral lithium amides. On the other hand, high diastereoselectivity (up to 100% de) and the low enantioselectivity were obtained from the aldol reaction of tropinone enolate with benzaldehyde differentiated by chiral lithium amides with extra electron donor atoms.<p>An analysis method to determine enantioselectivity from racemic α-hydroxytropinone was developed. That will, no doubt, benefit the further enantioselective α-hydroxylation reaction of tropinone.

The accomplishment of the γ-alkylation reaction from β-keto esters of tropinone and the enantioselective aziridine formation from nortropinone is first reported. This opened two new paths to develop tropinone enolate chemistry. One is indirect α-alkylation of tropinone, another is the nucleophilic attack from α-C enolate to the nitrogen atom.<p>Seven interesting chiral amines have been synthesized and applied into the enolate chemistry of two interesting precursors of synthesis of natural products: 1,4- cyclohexanedione monoethylene ketal and tropinone.<p>The aldol reaction between the lithium enolate of 1,4-cyclohexanedione monoethylene ketal and benzaldehyde demonstrated the high diastereoselectivity (up to 98% de) and the moderate to high enantioselectivity (up to 75% ee) induced by those chiral lithium amides. On the other hand, high diastereoselectivity (up to 100% de) and the low enantioselectivity were obtained from the aldol reaction of tropinone enolate with benzaldehyde differentiated by chiral lithium amides with extra electron donor atoms.<p>An analysis method to determine enantioselectivity from racemic α-hydroxytropinone was developed. That will, no doubt, benefit the further enantioselective α-hydroxylation reaction of tropinone.

This thesis is concerned with the development of methodology for the regioselective ring-opening of aziridines and aziridinium intermediates and its subsequent application to the asymmetric synthesis of &beta;-substituted-&alpha;-amino acids and 1,2,3,4-tetrahydroisoquinolines. Chapter 1 introduces methods for the formation of aziridines and aziridinium ions and focusses on their utility as intermediates in synthesis. Chapter 2 describes studies into the synthesis of aziridines from enantiopure &alpha;-hydroxy-&beta;-amino esters and their subsequent conversion to the corresponding &beta;-hydroxy-&alpha;-amino acids via either a regioselective ring-opening with Cl₃CCO₂H, or a rearrangement promoted by Cl3CCO2H. Application of this procedure to both syn- and anti-configured substrates enabled the syntheses of (S,S)-allo-threonine, (2R,3S)-threonine, (R,R)-3-hydroxyphenylalanine and (2S,3R)-3-hydroxyphenylalanine. Chapter 3 details attempts to truncate the synthesis described in Chapter 2 by investigating the synthesis of enantiopure anti-&beta;-hydroxy-&alpha;-amino acids via the intermediacy of aziridinium ions. These studies culminated in the development of a regioselective and stereospecific one-pot aziridinium formation and ring-opening protocol, leading to the synthesis of a range of C(3)-aryl and C(3)-alkyl substituted anti-&beta;-hydroxy-&alpha;-amino acids. Chapter 4 discusses the conversion of enantiopure anti-&alpha;-hydroxy-&beta;-amino esters to anti-&beta;-fluoro-&alpha;-amino esters via the regioselective and stereospecific ring-opening of an aziridinium intermediates in situ. The subsequent development of a one-pot deprotection strategy leads to a concise and expedient synthesis of anti-&beta;-fluorophenylalanines. The extension of this methodology to access a representative anti-&alpha;,&beta;-diamino acid is also demonstrated. Chapter 5 describes the development of a one-pot diastereoselective rearrangement of enantiopure &alpha;-hydroxy-&beta;-amino esters to 1,2,3,4-tetrahydroisoquinolines. The substrate scope of this reaction manifold is examined and application to the asymmetric synthesis of enantiopure 1,2,3,4-tetrahydroisoquinolines also discussed. Chapter 6 contains full experimental procedures and characterisation data for all compounds synthesised in Chapters 2, 3, 4 and 5.

This thesis investigates the chemistry of ammonia borane (NH3BH3) relevant to the development of hydrogen storage systems for vehicular applications. Because of its high hydrogen content and low molecular weight ammonia borane has the potential to meet stringent gravimetric hydrogen storage targets of gt;9 wt%. Two of the three moles of H2 in ammonia borane can be released under relatively mild conditions, with the highest gravimetric yield obtained in the solid-state. However, ammonia borane does not deliver sufficient H2 at practical temperatures and the products formed upon H2 loss are not amenable to regeneration back to the parent compound. The literature synthesis of ammonia borane was modified to facilitate large scale synthesis, and the deuterated analogues ND3BH3 and NH3BD3 were prepared for the purpose of mechanistic studies. The effect of lithium amide on the kinetics of dehydrogenation of ammonia borane was assessed by means of solid-state reaction in a series of specific molar ratios. Upon mixing lithium amide and ammonia borane, an exothermic reaction ensued resulting in the formation of a weakly bound adduct with an H2N...BH3-NH3 environment. Thermal decomposition at or above temperatures of 50eg;C of this phase was shown to liberate gt;9 wt% H2. The mechanism of hydrogen evolution was investigated by means of reacting lithium amide and deuterated ammonia borane isotopologues, followed by analysis of the isotopic composition of evolved gaseous products by mass spectrometry. From these results, an intermolecular multi-step reaction mechanism was proposed, with the rates of the first stage strongly dependent on the concentration of lithium amide present. Compounds exhibiting a BN3 environment (identified by means of solid-state sup1;sup1;B NMR spectroscopy) were formed during the first stage, and subsequently cross link to form a non-volatile solid. Further heating of this non-volatile solid phase ultimately resulted in the formation of crystalline Li3BN2 - identified by means of powder X-ray diffractometry. This compound has been identified as a potential hydrogen storage material due to its lightweight and theoretically high hydrogen content. It may also be amenable to hydrogen re-absorption. The LiNH2/CH3NH2BH3 system was also investigated. Thermal decomposition occurred through the same mechanism described for the LiNH2/NH3BH3 system to theoretically evolve gt;8 wt% hydrogen. The gases evolved on thermal decomposition were predominantly H2 with traces of methane detected by mass spectrometry.

In this dissertation, hydrogen storage enhancement in hypercrosslinked polystyrene, effects of single walled carbon nanotubes (SWCNTs) supported ruthenium (Ru) catalyst on the kinetics and ammonia suppression in the LiNH2-MgH2 complex hydride system and the accuracy of hydrogen storage measurements are investigated in detail. High surface area physisorption materials are of interest for room temperature hydrogen storage enhancement by spillover. Six different commercially available hypercrosslinked polystyrenes are screened by considering the specific surface area, average pore size, pore volume, and adsorption enthalpy. MN270 is selected mainly due to its high surface area and narrow pores for investigation of the spillover enhancement at room temperature. Two different platinum (Pt) doped MN270 samples are prepared by wet impregnation (MN270-6wt%Pt) and bridge building technique (MN270-bridged) with an average Pt particle size of 3.9 and 9.9nm, respectively, as obtained from X-ray diffraction analysis. Pt doping altered the surface property of MN270, and reduced the nitrogen and hydrogen uptake at 77 K and 1 atm due to pore blocking. The room temperature hydrogen uptake at 100 atm demonstrated a 10% enhancement for the MN270-bridged (0.36 wt. %) compared to the pristine MN270 (0.32 wt. %), but did not show any enhancement for the MN270-6wt%Pt under the same conditions. The hydrogen uptake of MN270-bridged has little value for practical applications; however, it showed the effectiveness of the bridge building technique. The LiNH2 - MgH2 (2:1.1) complex metal hydride system (Li-Mg-N-H), which is prepared by high energy ball milling, is investigated in terms of the hydrogen ab/desorption kinetics and the concomitant NH3 emission levels. By selecting more intense ball milling parameters, the hydrogen ab/desorption kinetics were improved and the NH3 emission reduced. However, it is shown that NH3 emission cannot be completely eliminated by ball milling. The hydrogen desorption kinetics of the Li-Mg-N-H system is much faster than the absorption kinetics at a specific T and P, but the desorption kinetics degraded considerably over a number of cycles as opposed to the stabilized absorption kinetics. Furthermore, SWCNTs and 20 wt. % Ru doped SWCNTs (SWCNT-20Ru) are utilized as catalysts to study their effects on NH3 emission and kinetics characteristics of the Li-Mg-N-H system. The SWCNT doped sample did not show any kinetics improvement, whereas the SWCNT-20Ru doped sample showed similar kinetics performance as that of the base sample. More importantly, the presence of SWCNT increased the NH3 emission as compared to the base sample. On the other hand, SWCNT-20Ru doping reduced the NH3 emission compared to the SWCNT doping, but did not eliminate it completely. As revealed from the mass spectrometry signals, the SWCNT-20Ru catalyst starts to decompose NH3 at a temperature as low as 200°C. However, an optimal catalyst still needs to be developed by fine tuning the Ru particle size and the SWCNT structural properties to maximize its effectiveness to suppress NH3 release in the Li-Mg-N-H system. The design of a volumetric measurement apparatus is studied by means of an uncertainty analysis to provide guidelines for optimum hydrogen sorption measurements. The reservoir volume should be as small as possible (i.e., 10 cc) to minimize the uncertainty. In addition, the sample mass loading has a profound effect on the uncertainty and the optimum loading is a function of the sample's intrinsic storage capacity. In general, the higher the sample mass loading the lower is the uncertainty, regardless of any other parameters. In cases where the material to be tested is not available in gram quantities, the use of high accuracy pressure and temperature transducers significantly mitigates the uncertainty in the sample's hydrogen uptake. Above all, the thermal equilibration time is an important parameter for high accuracy measurements and needs to be taken into consideration at the start of the measurements. Based on computational analysis, a 5 min wait time is required for achieving thermal equilibrium when the instrument enclosure temperature is different than the ambient temperature.

This thesis is concerned with the application of the conjugate addition of functionalised lithium amides in the asymmetric syntheses of (−)-morphine and all members of the homalium alkaloids. Chapter 1 introduces the conjugate addition reaction as an important bond forming reaction, and explores its utility in the asymmetric synthesis of a variety of natural products. The conjugate addition of secondary lithium amides derived from α-methylbenzylamine is discussed, along with its application to the asymmetric synthesis of alkaloids. Chapter 2 describes two distinct attempts towards the asymmetric synthesis of (−)-morphine, both reliant upon the lithium amide conjugate addition and an intramolecular Diels-Alder reaction to set the five required stereogenic centres. The use of the novel and highly functionalised reagent lithium (R)-N-[2′-(7-methoxybenzofuran-3-yl)ethyl]-N-(α-methylbenzyl)amide and its derivatives is reported. Chapter 3 focuses on the use of the novel reagent lithium (R)-N-(3-chloroprop-1-yl)-N-(α-methylbenzyl)amide and its derivatives in the asymmetric synthesis of two of the homalium alkaloids, (−)-(S,S)-homaline and (−)-(R,R)-hopromine, culminating in the most efficient syntheses of these alkaloids to date. Further, a sample of the (4′R,4′′S)-diastereoisomer of hopromine was synthesised, serving to confirm the proposed absolute configuration within natural (−)-(R,R)-hopromine. Chapter 4 extends the methodology developed in chapter 3 to the asymmetric synthesis of all possible diastereoisomers of the remaining homalium alkaloids, (−)-hopromalinol and (−)-hoprominol. These syntheses were used to propose the absolute configurations within these alkaloids, and therefore represented the first asymmetric syntheses of natural (−)-(4′S,4″R,2‴R)-hopromalinol and (−)-(R,R,R)-hoprominol. Chapter 5 contains full experimental procedures and characterisation data for all compounds synthesised in Chapters 2, 3 and 4.