by Huichang Zhang. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1996. / Includes bibliographical references (leaves 114-130). / Acknowledgment --- p.i / Abstract --- p.ii / Abbreviations --- p.iii / Table of Contents --- p.iv-v / Chapter Chapter I --- Introduction --- p.1 / Chapter I --- The basis of asymmetric catalysis --- p.6 / Chapter II --- Chiral catalyst --- p.8 / Chapter II-I --- Center metal --- p.9 / Chapter II-II --- Chiral ligand --- p.10 / Chapter III --- Structural analysis of effective chiral ligands --- p.13 / Chapter III-I --- Monodentate ligand --- p.15 / Chapter III-II --- Bidentate Ligand --- p.16 / Chapter 1 --- Bidentate phosphine ligand --- p.16 / Chapter 2 --- Bidentate oxygen ligand --- p.17 / Chapter 3 --- Bidentate nitrogen ligand --- p.19 / Chapter 4 --- "Bidentate ligand with N, 0，P, or S donor atom" --- p.21 / Chapter III-III --- Potentially tridentate ligand --- p.22 / Chapter III-IV --- Potentially tetradentate ligand --- p.23 / Chapter IV --- Tentative conclusions on the effect of structural elements --- p.24 / Chapter Chapter II --- "Design, synthesis and resolution of novel chiral pyridylphenols" --- p.27 / Chapter I --- Design of chiral ligand --- p.27 / Chapter II --- Synthesis of chiral ligands --- p.29 / Chapter II-I --- "Synthesis of the chiral N, O-donor ligands" --- p.29 / Chapter 1 --- Synthesis of the chiral ligands 75a-75c --- p.29 / Chapter 2 --- Synthesis of the chiral ligands 93a and 93b --- p.37 / Chapter 3 --- Synthesis of the chiral ligands 97a-97c --- p.41 / Chapter II-II --- "Synthesis of the chiral N, P-donor ligand 98 and N, S-donor ligand 101" --- p.42 / Chapter III --- Resolution of racemates of chiral ligands --- p.44 / Chapter III-I --- Resolution of of the pyridylphenol 75b --- p.44 / Chapter III-II --- Resolution of of the pyridylphenol 93a --- p.48 / Chapter III-III --- Racemization study of 75b and 93a --- p.52 / Chapter 1 --- Racemization test of 75b --- p.52 / Chapter 2 --- Racemization test of 93a --- p.52 / Chapter Chapter III --- Asymmetric addition of diethylzinc to aromatic aldehydes catalyzed by chiral pyridylphenols / Chapter I --- Backgound --- p.53 / Chapter II --- Asmmetric addition of Et2Zn to aldehydes catalyzed by chiral pyridylphenols --- p.61 / Chapter II-I --- Asmmetric addition of Et2Zn to aldehydes catalyzed by (R)-(+)-75b --- p.61 / Chapter 1 --- The influence of the solvent --- p.61 / Chapter 2 --- The influence of the reaction temperature --- p.64 / Chapter 3 --- The influence of the concentration of catalyst --- p.66 / Chapter 4 --- Electronic effect on the enantioselectivity of asymmetric addition of Et2Zn to aromatic aldehydes --- p.67 / Chapter II-II --- Asmmetric addition of Et2Zn to aldehydes catalyzed by (5)-(+)-75b --- p.73 / Chapter II-III --- Asmmetric addition of Et2Zn to aldehydes catalyzed by (R)-(+)-93a --- p.75 / Chapter III --- Conclusions --- p.78 / Chapter Chapter V --- Experimental Section --- p.79 / References --- p.114 / NMR Spectra --- p.131

by Fuk Yee Kwong. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2000. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Chiral amine motifs are found in many bioactive compounds and therefore strategies for their direct asymmetric synthesis are of great interest. Alongside traditional chemical methods, biocatalysis serves as an important tool for the formation of these compounds that can confer the benefits of sustainable catalyst supply and mild reaction conditions. This thesis describes the application of imine reductase (IRED) biocatalysts for the asymmetric reduction of pre-formed imines and the reductive amination of carbonyl compounds to produce chiral amines. These enzymes are relatively recent additions to the toolbox of biocatalysts for chiral amine synthesis and therefore their scope and application is still very much being explored. The research carried out as part of this PhD is presented as a series of manuscripts that have either been published or are planned for submission to peer-reviewed journals. The choice of presenting this thesis in journal format was made because a considerable body of the candidate's PhD research has been published, with the rest planned for publication in the near future. Furthermore, the compiled review articles and research papers lend themselves to a clear thesis narrative and, combined, have taken considerable time and effort to prepare, equal to that of a traditional thesis format. The contents are organised as follows: Chapter 1: an introduction to biocatalysis and its impact on sustainable chemical manufacturing; Chapter 2: a review assessing the current state of the art in imine reductase biocatalysts; Chapter 3: a perspective on the design and implementation of biocatalytic cascades; Chapter 4: a research article on the application of IREDs in a biocatalytic cascade for the synthesis of chiral piperidine and pyrrolidine frameworks; Chapter 5: aims of the PhD project; Chapter 6: a research article on the discovery and investigation of a reductive aminase (RedAm) found within the IRED family; Chapter 7: a research article on the screening of a diverse set of novel IREDs for their ability to facilitate reductive amination; Chapter 8: a research article on the synthesis of complex bulky dibenz[c,e]azepine compounds using IRED and transaminase biocatalysts; Chapter 9: a summary and outlook; Chapter 10: manuscript supporting information further detailing experimental work; Appendix: list of other publications resulting from this doctoral research.

We consider a pure exchange economy with asymmetric information where individual behavior exhibits ambiguity aversion along the line of maximin expected utility decision making. For such economies we introduce different notions of maximin value allocations. We also introduce a strong notion of (maximin) incentive compatibility. We prove existence and incentive compatibility of the maximin value allocation, when the economy's state space is either finite or non-finite. In the latter case, we provide two different existence results: assuming first countable and then uncountable infinitely many states of nature of the world. We conclude that unlike the Bayesian value allocation approach, incentive compatibility is related to efficiency rather than to direct exchange of information.

2-Pyridinyl-2-pyrazinylmethanone (L4) is able to exist in the neat ketone form and gem-diol form (2-C5H4N)C(OH) 2(2-C4H3N2) (L4a) in its Ag(I) and Cu(II) complexes. Two isostructural Cu(II) complexes [Cu(L4 a)2X2·2H2O, X = C lO4-, BF4-] with the L4a ligand taking the chelating mode are formed, in which the different linkage modes of lattice water molecules between the Cu(L4 a)22+ units lead to different space groups in crystallization. Through versatile anion-pi(pyrazinyl ring) and hydrogen-bonding interactions, the Cu(L4a)22+ units are assembled into distinct 3-D metal-organic hybrid frameworks in these two complexes. Different ligation modes of L4 in its neat ketone and gem-diol forms are found in its silver(I) complexes that exhibit diverse network structures. / By tuning the counter anion, mu2-bridging 2,6-pyridinediylbis(4-pyridinyl)methanone (L2) via two terminal 4-pyridyl N atoms links Ag(I) ions into two distinct structural motifs in its silver(I) complexes, namely infinite helical chain and metallacyclophane, which are further assembled into higher-dimensional metal-organic frameworks through Ag···Ag, pi···pi, hydrogen-bonding, Ag···O=C, carbonyl···carbonyl, as well as unconventional anion-pi(pyridyl ring) interactions. Intermolecular dipolar carbonyl···carbonyl interaction of three principal types serves as a common dominant non-covalent interaction in the supramolecular conglomeration of these complexes. / Di-2-pyrazinylmethanone (L3) readily undergoes metal-assisted hydration reaction in its Ag(I), Cu(II), Co(II) and Cd(II) complexes, and is potentially useful for the construction of extended coordination networks with its gem-diol (2-C4H3N2)2C(OH) 2 (L3a) or anionic (2-C4H3N 2)2C(OH)CO- (L3b) form as an architectural moiety. A sheet-like net, an alpha-polonium topology of the NaCl-type and a rare 1-D nanotubular coordination architecture has been generated in its Ag(I) complexes through the tuning of counter-anions. Three isostructural complexes Cu(L3a)2X2· nH2O (n = 4.5; X = ClO 4-, BF4-, PF 6-) have been obtained and characterized. The 3-D host frameworks of these complexes are constructed from the linkage of mononuclear Cu(L3a)22+ metallotectons through a combination of hydrogen-bonding and anion-pi interactions, leading to honeycomb-like channels that accommodate guest water molecules. A cubane-like Co(II) cluster stabilized by L3b and the topological structure of Cd(II) complexes with L3a have also been obtained. / Di-2-pyridinylmethanone (di-2-pyridyl ketone) is a well-known versatile ligand among the basic building blocks for the construction of metal-organic hybrid materials. It can exist in its neat form, or in the hydrated gem-diol and alcoholated hemiketal forms. In this thesis, through modification of the heterocyclic ring and the bridging functional group, we have systematically synthesized a series of transition metal complexes of five carbonyl-bridged heterocycles (L1-L5) (see P. xi) and two structural analogs with sulfinyl and sulfonyl bridging groups (L6-L7), which are expected to provide flexible coordination bonding and additional non-covalent interactions in the generation of metal-organic hybrid frameworks. / In the two mononuclear Cu(II) complexes of 2,6-pyridinediylbis(3-pyridinyl)methanone (L1) with the ligand taking a chelating mode, four distinct types of unconventional intermolecular C=O···pi interactions between the carbonyl and pyridyl rings were identified. Moreover, the mu2-bridging L1 via two 3-pyridyl N atoms proves to be an excellent building block for the construction of disilver(I) metallacyclophanes with a [Ag2(L1) 2]2+ skeleton in a series silver(I) complexes. The [Ag 2(L1)2]2+ metallacycle functions as a secondary building unit to form infinite chains through Ag···O=C or argentophilic interactions, which are further assembled into a 3-D supramolecular structure via collective weak interactions including the anion-pi interaction. The employment of different Cd(II) and Hg(II) salts to react with the flexible L1 ligand has resulted in infinite chain, mononuclear, and 3-D network structures, in which L1 takes eta1-terminal, N,N-chelating, and mu2- and mu3-bridging modes. In these complexes, C--H···O, C--H···Cl--M hydrogen bonding, pi···pi, carbonyl···carbonyl, O(perchlorate)···C=O, as well as unconventional anion···pi(pyridyl ring) interactions, play important roles in consolidation of the supramolecular frameworks. / Sulfinyldipyrazine (L7) is capable of forming intriguing architectures in various sivler(I) salts, including a series of coordination polymers exhibiting (4,4) net, infinite chain and 3-D framework structures. A remarkable characteristic of L7 is that the electron-deficient pyrazinyl ring and the sulfonyl group provide potential bonding sites for lone-pair-aromatic interactions in the supramolecular assemblies, such as anion-pi and S=O···pi(pyrazinyl ring) interactions. The S=O moiety of the sulfonyl group exhibits an affinity for the pyrazinyl ring, which is evidenced by the existence of two types of such interaction in the silver(I) complexes of L7. (Abstract shortened by UMI.) / by Wan, Chongqing. / Adviser: Thomas C. W. Mak. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3504. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 172-190). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

The palladium-catalysed asymmetric allylic alkylation is a mild and versatile bond forming reaction between a nucleophile and allylic electrophile. The wide scope of nucleophiles used, and the high regio- and stereoselectivity obtainable renders this transformation an important technique in enantioselective synthesis. The mechanism is known to go via a key palladium π-allyl intermediate, followed by nucleophilic addition occurring at the terminal allylic carbon. Both the formation of the palladium π-allyl, and the nucleophilic addition to generate the alkylated product and palladium(0) proceed with high levels of inversion of stereochemistry, and both provide an opportunity for the induction of stereochemistry. However in the case of ligand controlled nucleophilic addition memory effects have been observed. The epimerisation of the palladium π-allyl before nucleophilic attack is key to achieving high levels of selectivity when racemic starting materials and chiral ligands are employed. Previous work in the Lloyd-Jones group has determined that prolonging the lifetime of the palladium π-allyl species, either by the use of weakly coordinating counter ions or slow addition of the nucleophile reduces this memory effect, however increasing the rate of epimerisation would have a result in a similar effect. One of the mechanisms resulting in the epimerisation of the palladium π-allyl species is mediated by palladium(0), however the details of the mechanism are not well understood. We describe the synthesis of a diastereotopic palladium cyclohexenyl ester and labelled the complex with 108palladium and d3 at the cyclohexenyl ester. Using simultaneous 31P NMR and mass spectrometry, we have acquired strong evidence against mechanisms involving a single electron transfer, as proposed by Stille, of formation of a dinuclear palladium(I) species followed by an inversion event, and we have gained evidence supporting the direct nucleophilic addition of the palladium(0), resulting in inversion of stereochemistry. The differences in rates of nucleophilic attack involving monodentate and bidentate phosphine ligands on both the palladium I-cyclohexenyl ester have also been explored. Throughout the mechanistic investigation, it was noted that the 31P NMR spectroscopy experiment used gave non-quantitative results, and in fact the differences in quantification of the species varied with the spectrometer used. We also describe our investigations into where these differences arise from and an optimum set of parameters for quantitative 31P NMR spectroscopy. The conclusions are also applicable to other heternuclear NMR spectroscopic experiments.

Quantile regression (QR) (Koenker and Bassett, 1978), as a comprehensive extension to standard mean regression, has been steadily promoted from both theoretical and applied aspects. Bayesian quantile regression (BQR), which deals with unknown parameter estimation and model uncertainty, is a newly proposed tool of QR. This thesis aims to make some novel contributions to the following three issues related to QR. First, whereas QR for continuous responses has received much attention in literatures, QR for discrete responses has received far less attention. Second, conventional QR methods often show that QR curves crossing lead to invalid distributions for the response. In particular, given a set of covariates, it may turn out, for example, that the predicted 95th percentile of the response is smaller than the 90th percentile for some values of the covariates. Third, mean-based clustering methods are widely developed, but need improvements to deal with clustering extreme-type, heavy tailed-type or outliers problems. This thesis focuses on methods developed over these three challenges: modelling quantile regression with discrete responses, ensuring non-crossing quantile curves for any given sample and modelling tails for collinear data with outliers. The main contributions are listed as below: * The first challenge is studied in Chapter 2, in which a general method for Bayesian inference of regression models beyond the mean with discrete responses is developed. In particular, this method is developed for both Bayesian quantile regression and Bayesian expectile regression. This method provides a direct Bayesian approach to these regression models with a simple and intuitive interpretation of the regression results. The posterior distribution under this approach is shown to not only be coherent to the response variable, irrespective of its true distribution, but also proper in relation to improper priors for unknown model parameters. * Chapter 3 investigates a new kernel-weighted likelihood smoothing quantile regression method. The likelihood is based on a normal scale-mixture representation of an asymmetric Laplace distribution (ALD). This approach benefits of the same good design adaptation just as the local quantile regression (Spokoiny et al., 2014) does and ensures non-crossing quantile curves for any given sample. * In Chapter 4, we introduce an asymmetric Laplace distribution to model the response variable using profile regression, a Bayesian non-parametric model for clustering responses and covariates simultaneously. This development allows us to model more accurately for clusters which are asymmetric and predict more accurately for extreme values of the response variable and/or outliers. In addition to the three major aforementioned challenges, this thesis also addresses other important issues such as smoothing extreme quantile curves and avoiding insensitive to heteroscedastic errors as well as outliers in the response variable. The performances of all the three developments are evaluated via both simulation studies and real data analysis.

This thesis describes expansion of the ability of isothioureas to act as organocatalysts in formal [2+2]-, [3+2]- and [4+2]-cycloadditions between carboxylic acids and various acceptors via Type I ammonium enolate intermediates. Chapter 2 describes the optimisation and investigation of [2+2]-cycloadditions from ammonium enolates and N-sulfonylimines as the two components. The development of this methodology allows successful access to highly stereodefined β-lactams and, following in situ ring-opening, β-aminoesters. The products are obtained from either preformed homoanhydrides or directly from carboxylic acids, using open flask conditions, from simple, bench-stable starting materials and is scalable. A variety of anti-β-lactams (21 examples, 46-68% yield, up to >95:5 dr, 21->99% ee) and β-aminoesters (9 examples, 44-74% yield, up to >95:5 dr, 68-92% ee) were accessed in moderate yield, excellent diastereo- and good enantioselectivity. This represents an improved route to anti-β-lactams over previously described ketene and N-triflyl imine based methods. Chapter 3 subsequently describes studies focussed on the use of ester surrogates in the formal [4+2]-cycloaddition reactions of isothiourea generated Type I ammonium enolates. Iso-propylphosphonate 163 proved highly effective as the four-component in this process, which following the in situ ring-opening of the initial dihydropyranone product allowed isolation of a range of novel diester products which were previously unobtainable using this methodology. The products were accessed in moderate to excellent yields, excellent diastereo- and enantiocontrol (9 examples, 12-63% yield, up to >95:5 dr, 67-99% ee) with this process also amenable to a large scale. Furthermore, selective reduction and acid-catalysed cyclisation allowed access to δ-lactone products in good yield with retention of stereocontrol. Finally, Chapter 4 describes work on isothiourea-catalysed formal [3+2]-cycloadditions of oxaziridines and acetic anhydrides gave access to stereodefined five-membered oxazolidin-4-one heterocycles. In this case, the use of preformed homoanhydrides and an inorganic base was imperitive to avoid reduction of the oxaziridine starting material. The oxazolidin-4-one products could be accessed in excellent yield and ee however poor dr (13 examples, 63-96% yield, up to 59:41 dr anti:syn, up to >99% ee for both diastereoisomers). Following isolation, reduction of these heterocycles allowed access to enantioenriched diols with little loss in stereocontrol. Mechanistic analysis has shown that an improvement in diasterocontrol can be obtained by the use of an enantioenriched oxaziridine, demonstrating the stereospecificity of this process.

Wu, Kwun Wang. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 76-79). / Abstracts in English and Chinese. / Acknowledgment --- p.i / Table of Contents --- p.ii / Abstract --- p.iii / Abstract (Chinese Version) --- p.v / Abbreviation --- p.vi / Chapter 1. --- Introduction --- p.1 / Chapter 1.1 --- Organocatalysis --- p.1 / Chapter 1.2 --- Diels-Alder reaction --- p.3 / Chapter 1.3 --- Intramolecular Diels-Alder (IMDA) reaction --- p.4 / Chapter 1.4 --- Methods for obtaining optical active product --- p.5 / Chapter 2. --- Results and Discussion - Synthetic Studies of Carbocycles from Carbohydrates --- p.15 / Chapter 2.1 --- Organocatalyst dervied from D-arabinose --- p.15 / Chapter 2.2 --- Synthesis of Intramolecular Diels-Alder reaction substrates --- p.28 / Chapter 2.3 --- Organocatalytic enantioselective IMDA reaction --- p.36 / Chapter 4. --- Conclusion --- p.43 / Chapter 5. --- Experimental --- p.45 / Chapter 6. --- References --- p.76 / Appendix --- p.80 / HPLC chromatogram --- p.1-1 - 1-2 / NMR spectra --- p.II-1 - II-36

基於本課題組以前的工作，通過以廉價易得的D-阿拉伯糖為起始原料，我們進一步探討和優化了一條快速有效地合成手性胺類催化劑的有效路線（81-84）。在第一代催化劑的基礎上，我們設計合成了含有雙環碳酸酯結構的新型胺類催化劑（98）。 / 通過製備叁烯醛類底物，我們探討研究了一系類分子內DA反應的不對稱催化條件，如溶劑、共酸和水等。我們發現水的存在基本上不會影響反應的對映體選擇性，但對反應的非對映體選擇性卻具有極其重要的影響。同時我們也研究了各催化劑的手性誘導能力。 / 通過以催化劑（81）的高氯酸鹽和肉桂醛反應製備了反應中間體亞胺鹽，并經NOE試驗確認了其幾何構型。製備的胺類催化劑对空气和水不敏感，同時也能穩定存在於過量酸（1.2 eq）的環境中。 / 此外，我們也初步探討了由糖衍生的胺類催化劑催化的分子間DA反應。這些不成功的嘗試表明胺類催化的分子間DA反應需要更高的活化能，因此可能需要活性更強的催化劑。 / Based on our previous work, we further explored and optimized an efficient route to prepare chiral amine catalysts from inexpensive and commercially available D-arabinose with good yield (81-84). On the basis of our 1st generation catalysts, a novel amine catalyst with bicyclic carbonate structure was obtained (98). / By preparing trienal substrates, a series of asymmetric catalysis conditions for Intramolecular Diels-Alder (IMDA) reactions were investigated, such as solvent, co-acid, water, et.al. Water was found to have a significant effect to the diastereoselectivity and without losing the enantioselectivity. The chiral induction capability of the synthesized catalysts was also assessed. / The reactive intermediate of iminium salt was prepared from perchlorate salt of catalyst 81 with cinnamaldehyde, and the geometry of the iminium ion was proved by NOE experiment. The prepared catalysts were insensitive to moisture and oxygen and also stable even with excess amount of perchloric acid (1.2 eq). / A preliminary investigation to the amine catalyzed Intermolecular Diels-Alder reaction was also tried. The unsuccessful trials demonstrated that amine catalyzed Intermolecular Diels-Alder reaction requires higher activation energy. Some more reactive catalysts may be needed for this type of reaction. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Xiao, Qicai. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 76-82). / Abstracts also in Chinese. / Acknowledgment --- p.i / Table of Contents --- p.ii / Abstract --- p.iv / Abstract (Chinese Version) --- p.v / Abbreviation --- p.vi / Chapter 1. --- Introduction --- p.1 / Chapter 1.1 --- General background --- p.1 / Chapter 1.2 --- Chiral amine catalyzed organic reactions --- p.3 / Chapter 1.2.1 --- LUMO-Lowing activation (Iminium Catalysis) --- p.4 / Chapter 1.2.2 --- HOMO-Raising activation (Enamine Catalysis) --- p.6 / Chapter 1.2.3 --- SOMO activation (SOMO Catalysis) --- p.8 / Chapter 1.3 --- Diels-Alder reaction --- p.10 / Chapter 1.4 --- Chiral amine catalysts --- p.13 / Chapter 1.5 --- Objective of this study --- p.14 / Chapter 2. --- Results and Discussion --- p.16 / Chapter 2.1 --- Optimization and synthesis of amine catalysts from D-arabinose --- p.16 / Chapter 2.2 --- Synthesis of substrates for intramolecular Diels-Alder reactions --- p.23 / Chapter 2.3 --- Enantioselective organocatalytic intramolecular Diels-Alder (IMDA) reactions --- p.28 / Chapter 2.4 --- Determination the geometry of the iminium ion --- p.38 / Chapter 2.5 --- Determination the stereochemistry of the major and minor product for the organocatalyzed IMDA reaction --- p.41 / Chapter 2.6 --- Exploring the epimerization effect --- p.43 / Chapter 2.7 --- Amine catalyzed intermolecular Diels-Alder reactions --- p.46 / Chapter 3. --- Conclusion --- p.50 / Chapter 4. --- Experimental Section --- p.53 / Chapter 5. --- References --- p.76 / Chapter 6. --- Appendix --- p.83 / Chapter 6.1 --- HPLC spectra and data --- p.84 / Chapter 6.2 --- NMR spectra --- p.87 / Chapter 6.3 --- X-ray crystallographic structure and data --- p.126