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Due to the ever increasing demand for the production of enantiopure drugs and biologically active compounds, the study of asymmetric synthesis and the production of more efficient and cost effective methods of obtaining chiral compounds suggests that there are expanding opportunities for Organic Chemists in this field. Of the broad range of chiral technologies available today for the synthesis of even the most complex multi-centre chiral molecules, the use of chiral auxiliaries continues to remain an important means of obtaining single enantiomer chiral compounds. In this investigation, the imidazolidinone chiral auxiliary (i) was synthesised in order to determine its efficiency and ability to transfer chiral information in Diels-Alder cycloaddition reactions. The products of such reactions are extensively used in the synthesis of natural compounds and pharmaceutical drugs. The synthesis of the imidazolidinone auxiliary is described and mention is made of the fact that the starting materials are cheap and readily available in both enantiomeric forms. The pathway involves only a single reaction that is easily carried out in moderate yields of 60-65%. An adaptation of this auxiliary is the cyclohexyl derivative (ii) which was obtained in a single hydrogenation step of (i) in very high yields (98%). This was compared to the synthesis of the bornane-1O,2-sultam auxiliary (ii). Although the starting materials are also cheap and readily available, there are more reaction steps involved. The synthesis of the imidazolidinone auxiliary proved to be much more simple as well as more time and cost effective. The huge advantage of these auxiliaries is the fact that they are both crystalline which facilitates their purification and that of their derivatives. A possible deficiency of the imidazolidinone auxiliary and the bornane-1O,2-sultam auxiliary was the fact that substitution reaction yields with various a,b-unsaturated acyl chlorides were consistently low (<50%). A major by-product of the acylation reaction was a 'double-adduct' compound that severely affected the reaction yields. This was overcome by employing a new method of acylation developed during the course of this research. It involves the use of DABCO as base with reaction yields between 60 and 98%. In addition to this, reaction conditions were mild and work up procedures simple. The N-acylimidazolidinone auxiliary proved to be extremely successful in Diels-Alder reactions with cyclopentadiene With results equalling those obtained with the well known and highly publicised bornane-10,2-sultam auxiliary. The scope of the N-acylimidazolidinone auxiliary in these reactions included the use of a- and b- substituted dienophiles. Although reactions with a-methyl and b-methyl substituted dienophiles were successful, the auxiliary proved to be unreactive with b-phenyl and b,b-dimethyl substituted dienophiles. The scope of dienes used was extended to include the relatively less reactive isoprene and 2,3-dimethyl-l,3-butadiene. Only the former reacted successfully in Diels-Alder reactions with the N-acylimidazolidinone auxiliary. Crystallinity was imparted to all the products except for the cyclohexyl derivative whose cycloaddition adducts only solidified on standing. The Diels-Alder adducts were successfully cleaved under standard reaction conditions to give products with ee's ranging from 95:5 to 99:1. This investigation also includes the use of the tertiary amine, DABCO, as a catalyst in the Diels-Alder reaction with, specifically, the N-acryloylimidazolidinone chiral auxiliary. Most examples of Diels-Alder reactions involve the use of Lewis acids as a means of improving the rate and selectivity of Diels-Alder reactions. DABCO not only increased the reactivity of the N-acryloylimidazolidinone auxiliary towards cyclopentadiene, but selectivity was also observed. An explanation was put forward as to the mechanism of the reaction as well as to the source of selectivity. Selectivity was much more pronounced in Diels-Alder reactions with the N-acryloylimidazolidinone auxiliary than with the N-acryloylbornane-10,2-sultam auxiliary. It was predicted that DABCO catalysed reactions are amenable to large scale procedures. Due to the fact that the diastereomeric cycloadducts are easily purified by recrystallization or chromatography, and together with the practical advantages and mild reaction conditions this could render the DABCO methodology with the N-acryloylimidazolidinone auxiliary industrially viable. / Thesis (M.Sc.)-University of Natal, Pietermaritzburg, 1997.

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Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

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.

Este trabalho mostra uma série de reações para a síntese de naftacendionas, partindo da l-acetilamino-4-hidroxi-9,10-antraquinona e seu produto de oxidação, a 4-acetilamino-9a-acetoxi-l,9, 10-antracenotriona, em presença de Pb(OAc)4. Estudou-se o comportamento da 4-acetilamino-9a-acetoxi- 1,9,10-antracenotriona frente a reagentes nuclefílicos de diferente natureza. Estas reações permitem o isolamento e a preparação de uma série de novos derivados antracênicos., úteis como intermediários sintéticos para outros amino-hidroxi-antracenos. / In this master work have been shown a series of reactions concern an the synthesis of naphthacendiones, starting from the l-acetylamine-4-hydroxy-9,10-anlhraquinone and its oxydation product the 4-acelylamine-ga-aceloxy-l~9,10-anthracentriane in presence of Pb(OAc)4. The behavior of the 4-acelylamine-9a-acelaxy-l,9,10- anthracentrione against nucleophylic reagents of different .nature have been studied. These reactions permit the isolation and preparation of a series of new anthracene derivatives useful as synlhelic inlermediales through other amine-hydraxyanthracenes and for analytical applications.

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

Salvinorin A [(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(acetyloxy)-2-(3-furanyl)-dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naptho[2,1-c]pyran-7-carboxylic acid methyl ester] is a trans-neoclerodane diterpene from the leaves of the hallucinogenic Mexican sage Salvia divinorum and has been identified as the principal psychoactive component in this plant of traditional spiritual importance. Salvinorin A is the most potent naturally occurring hallucinogen found so far and is reported to act selectively as a ƒÛ-opioid receptor agonist. Synthetic modification of the natural product has contributed to a number of proposed pharmacophores to identify the key structural features necessary for biological activity and a direct strategy for the asymmetric synthesis of the natural product is desirable since it allows access to a more diverse range of analogues. An ambitious retrosynthetic study of salvinorin A indicated the C(3)-heterosubstituted furan as an appropriate starting material for a Diels-Alder approach towards the ketone ring of the natural product. An expedient and high yielding methodology for the preparation of 3-furylamines is described, allowing the flexible introduction of alkyl substituents in the C(5) position. Optically pure ephedrine isomers have been explored as chiral amine auxiliaries and have been successfully attached as 3-furylamine substituents using the general methodology described. The 3-furylamines are electron rich dienes that are highly reactive towards Diels-Alder cycloaddition reactions with methyl acrylate. Diastereoisomers of the 7-oxanorbornane species methyl 1-methyl-5-oxo-7-oxa-bicyclo[2.2.1]heptane-2-carboxylate were prepared as new compounds from the hydrolysis of Diels-Alder cycloadducts and are functionalised bicyclic intermediates to access the ketone of the natural product. Diels-Alder reactions between the non-racemic (2S)-ephedrine-derived furans and methyl acrylate gave spiro-oxazolidine adducts that underwent hydrolysis to give the desired ketone. X-ray crystallography data for the derivatised cycloadduct established diastereoselectivity in favor of the (1S,4S)-enantiomer, as desired for the asymmetric natural product synthesis. A procedure for the ether cleavage of methyl 1-methyl-5-oxo-7-oxa-bicyclo[2.2.1]heptane-2-carboxylate was required to access the convergent precursor methyl 5-acetoxy-2-methyl-4-oxocyclohex-2-enecarboxylate. Successful C-O cleavage was achieved using Lewis-acid catalysis with BBr3 followed by mixing with the hindered base 2,4,6-collidine to yield methyl 5-hydroxy-2-methyl-4-oxocyclohex-2-enecarboxylate albeit only at high dilution. Acetylation proceeded in excellent yield in the same reaction vessel to give methyl 1-methyl-5-oxo-7-oxa-bicyclo[2.2.1]heptane-2-carboxylate in excellent yield. The devised synthetic pathway is shown to successfully construct the ketone ring of salvinorin A and stereoselectivity for the (1S,4S)-enantiomer can be achieved using the ephedrine derived furans as desired for the asymmetric natural product synthesis. The ƒÔ-lactone ring 6-(furan-3-yl)-5,6-dihydro-4-methyl-3-vinylpyran-2-one was derived from rudimentary precursors as a convergent reagent to introduce the lactone ring of salvinorin A. A short synthesis for the racemic compound is described starting from the aldol reaction between 3-furaldehyde and acetone to give the 3-furfurol, 4-(furan-3-yl)-4-hydroxybutan-2-one in quantitative yield. The 3-furfurol was reacted to form the ƒÑ-bromovinyl ester, 1-(furan-3-yl)-3-oxobutyl 2-bromobut-3-enoate using a deconjugation/esterification protocol with 2-bromobut-3-enoyl chloride. Intramolecular ring closure to the ƒÔ-lactone was achieved using a Reformatsky reaction and dehydration under acidic conditions yielded the racemic convergent precursor 6-(furan-3-yl)-5,6-dihydro-4-methyl-3-vinylpyran-2-one in high yield. A possible strategy for joining the ketone and lactone fragments for the total synthesis of salvinorin A is proposed.