Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1982. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE / Includes bibliographical references. / by Steven Edward Hall. / Ph.D.

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

During the course of this work we have synthesized and evaluated a series of new enantiopure silyl triflmides as catalysts for asymmetric reactions. 3-Phenyl dialkylsilyl ketones, which were the key precursors to the target silyl triflmides were prepared by 1,4-addition of the corresponding silyl cuprate to enones, and resolved by chiral HPLC. Enantiopure trans silyl ketones were successfully reduced via the corresponding tosylhydrazones by the NaBH3CN/ZnCl2 system. However, due to an isomerization of the tosylhydrazone during the reaction, cis isomers (m = 0) were reduced via the corresponding dithioketals followed by desulfurization. The diastereoselective synthesis of enantiopure silyl triflimides from enantiomerically pure compounds has been also studied. The enantiopure trialkylsilyl triflimides were generated in situ by protodesilylation of the corresponding phenylsilanes with bis-(trifluoromethylsulfonyl)imide. The Diels-Alder reaction of methyl acrylate with cyclopentadiene was used as the model reaction for testing the new chiral catalysts : 1) Almost all silyl triflimides were efficient catalysts giving high yields and excellent diastereoselectivities in favour of the endo-isomer. 2) the best ee's (up to 56%) were obtained from catalysts carrying an aryl group directly attached to the cyclohexane ring (m = 0) which were much better than those obtained from catalysts carrying a benzyl-type group (m = 1). Interestingly catalysts of the same configuration carrying phenyl or naphthyl group gave cycloadducts of opposite configuration. 3) When m = 0, additional substituents at position-3 or 6 of the cyclohexyl ring had little influence on the ee. However, for m = 1, a methyl group at C2 increased the ee from 3% to 35%. 4) The replacement of the methyl groups connected to the silicon atom by bulkier ethyl groups decreased the ee (m = 0). 5) When m = 0, ee's for cycloaddition reactions of N,N-dimethyl acrylamide or acryloxazolidinone with cyclopentadiene were lower than those obtained with methyl acrylate.

Thesis (M.Sc.)--Memorial University of Newfoundland, 2005. / Bibliography: leaves 97-99.

This work was a kinetic study of the Diels-Alder reaction of isoprene with variously substituted benzalmalononitriles. Application of the Hammett equation, a linear free energy relationship, to the kinetic rate data yielded a value of 1.31 for rho. This was interpreted as meaning the transition state for this Diels-Alder reaction was probably of the concerted type, although the nonconcerted polar transition state could not be eliminated in one case by the data of this study.Ball State UniversityMuncie, IN 47306

The first comprehensive account of Diels-Alder reactions occurring by a simultaneous self-assembly of the components and catalysis of the reaction via a Lewis Acid (LA) is presented in this study. The synthetic usefulness of the intramolecularity achieved by temporary connection of DA reaction components has been combined with the benefits of LA catalysis to overcome the regio- and stereochemical diversities associated with DA reactions of unsymmetrically substituted dienes and dienophiles. LA's employed in this study act both as temporary connectors (by binding to LB sites of the diene and dienophile) and as catalysts (by complexation to oxygen of carbonyl moieties of the dienophiles). Formation of the tether, cycloaddition; and removal of the transient linker all occurs in a single operation.* To illustrate the high selectivity accomplished in this approach, an experimental model system consisting of unsymmetrically substituted dienol 6 and methoxy diene 397 and an unsymmetrically substituted dienophile (methyl acrylate, MAC) was designed. Thermal combination of either of these two dienes with MAC produces nearly equimolar mixtures of all four possible adducts illustrating the unselective nature of the reactions. Use of LA's to mediate the reaction between dienol 6 and MAC results in exclusive regio- and stereoselective formation of a single adduct. In contrast, application of the same LA's for the reaction between the methoxy diene and MAC either results in the formation of two 'endo' regioisomers in low yield or no reaction at all.* Exclusive formation of a single adduct for the reactions of 6 is attributed to a process in which the LA both pre-organizes the reactants and catalyzes the cycloaddition. This phenomenon is not expected to be observed in the reactions of the methoxy diene. The difference in the behavior of the two dienes is ascribed to the difference in their interactions with the LA's. Dienol 6 is able to bind covalently and irreversibly to the LA's while methoxy diene 397 is only able to co-ordinate to the LA's in a reversible manner. Mechanistic studies strongly support the self-assembled pathway and exclude other potential routes. Reactions of dienol 6 with other structurally suitable dienophiles under similar LA mediated conditions exhibit higher selectivities and reactivities in comparison with their uncatalyzed counterparts. Use of a structurally similar chiral dienol induces a highly diastereoselective cycloadditions with different dienophiles, whereas the thermal versions of the reactions again produce all possible adducts. The strategy has also been used for DA reactions of ' 2H'-thiopyran dienols with dienophiles 'N'-acroyl-2-oxazolidinone (NAO), ('E')-3-[3-(methoxycarbonyl)propenoyl]-1,3-oxazolidin-2 -one (MCPO), and 'N'-phenylmaleimide (NPM). Use of MgII is demonstrated to be effective to stereoselectively catalyze reactions which are unselective thermally or do not proceed at all. *Please refer to dissertation for diagrams.

(-)-Gymnodimine is a member of a growing family of spirocylic imine containing marine natural products. The construction of the complete skeleton of (-)- gymnodimine has been accomplished in a convergent manner in 23 steps (the longest linear sequence). A highly diastereo- and enantioselective Diels-Alder reaction employing bis(oxazoline)·Cu(II) catalyst provided the spirolactam core structure of gymnodimine bearing a quaternary carbon stereogenic center. An improved procedure for hydrostannylation of the hindered internal triple bond in 96a was discovered by slow addition of tributyltin hydride to minimize formation of hydrogenated byproduct. Fragment coupling featured a Nozaki-Hiyama-Kishi reaction between a vinyl iodide derived from the spirolactam and a tetrahydrofuran moiety. The macrocyclization was realized through a rather unusual intramolecular opening of an activated Ntosyllactam by an alkyllithium species generated in situ. The butenolide was appended through a vinylogous Mukaiyama aldol addition of silyloxyfuran 155 to the ketone 163 under meticulously controlled conditions. The generality of this process was explored in some detail. Addition of silyloxyfurans to cyclohexanones proceeds with moderate to good diastereoselectivities. The potential application of this process to the synthesis of butenolide and g-lactone containing natural products was demonstrated by further transformations of the addition adducts. Finally, toward our goal of developing an enzyme-linked immunosorbent assay (ELISA) for gymnodimine monitoring a hapten derived from the tetrahydrofuran has been synthesized. Even though the raised antibodies failed to recognize the natural product itself, the results provided some information regarding the essential structural elements of an efficient hapten.

Thesis (Ph.D.)--Memorial University of Newfoundland, 2001. / Bibliography: leaves 245-257.

Thesis (Ph. D.)--University of Chicago, Department of Chemistry, 2002. / Includes bibliographical references. Also available on the Internet.