A number of oxygenated heterocycles have been described in nature as having a myriad of biological activities. Owing to these biological activities and their complex structure, these compounds are of interest to us and the preparation of selected oxygenated heterocycles is described in this thesis. Three main sections form this thesis, with each representing a class of oxygenated heterocycle. The first part of the thesis deals with pyranonaphthoquinone analogues where a model study was performed to construct the skeleton of the isochromane kalafungin. The synthesis of isochromane 6,9-dimethoxy-3,3a,5,9b-tetrahydro-2H-furo[3,2-c]isochromen-2-one was successfully achieved from commercially available 2,5-dihydroxybenzoic acid in an overall yield of 9.5%. The key steps employed in the synthesis of the isochromane were a cross metathesis reaction between (2-allyl-3,6-dimethoxyphenyl)methanol and ethyl acrylate to afford the α,β-unsaturated ester (E)-ethyl-4-(2-(hydroxymethyl)-3,6-dimethoxyphenyl)but-2-enoate which, after several synthetic steps, was converted to the isochromane via a radical induced lactonization using a hypervalent iodine reagent. The success of this route led us to the preparation of iscochromane (3aR, 5R, 9bR)-6,9-dimethoxy-5-methyl-3,3a,5,9b-tetrahydro-2Hfuro[ 3,2-c]isochromen-2-one. Our initial aim was to enzymatically resolve intermediate racemic alcohol 1-(2-allyl-3,6-dimethoxyphenyl)ethanol, however, the use of Candida antarctica lipase B (CALB) to facilitate the kinetic resolution was not as successful as we hoped. Therefore, using racemic alcohol 1-(2-allyl-3,6-dimethoxyphenyl)ethanol and the key reaction conditions developed in the model study of 6,9-dimethoxy-3,3a,5,9b-tetrahydro-2H-furo[3,2-c]isochromen-2-one, we successfully prepared isochromane (3aR, 5R, 9bR)-6,9-dimethoxy-5-methyl-3,3a,5,9btetrahydro 2H-furo[3,2-c]isochromen-2-one in an overall yield of 0.4%, albeit racemically. The second part of this thesis involved the use of nitroalkanes as precursors to spiroketals. In this section, we managed to successfully elucidate the mechanism of a novel Nef reaction previously described in our laboratories using three different substrates. The key steps involved during the elucidation of the mechanism were a Henry condensation reaction and a key modified Nef reaction. The preparation of the spiroketal skeleton of the griseusins was also attempted. The last part of this PhD thesis focused on the formation of angucycline analogues, specifically analogues related to the landomycins. We have successfully managed to prepare landomycin analogues tetraphene-7,12-dione, 3-methoxytetraphene-7,12-dione and 3,8-dimethoxytetraphene-7,12-dione. A Suzuki reaction followed by a Wittig reaction, isomerisation and final ring closing metathesis allowed for the smooth preparation of these analogues. The preparation of related analogues bearing seven-membered rings has also been achieved and is described.

MSc., Faculty of Science, University of the Witwatersrand, 2011 / The 2-isopropenyl-2,3-dihydrobenzofuran moiety is found in many naturally occurring compounds including rotenone, a complex pentacyclic molecule isolated from several leguminous plants of the Derris and Lonchocarpus species. Interest in rotenone stems from the fact that it possesses significant pesticidal and piscicidal properties which have been employed for centuries. Furthermore, as it has three stereogenic centres, rotenone poses an interesting and challenging synthetic target for organic chemists. Although various syntheses of this natural compound have been reported, none of these were stereoselective. The first stereoselective total synthesis of rotenone is described in this dissertation. Initially, a model study was conducted in which the simplest of the natural rotenoids, munduserone, was synthesised. The key step in this transformation involves the use of a platinum catalysed 6-endo-hydroarylation reaction of an alkynone intermediate, thus affording munduserone in 6 steps and an overall yield of 23%. We then attended to the synthesis of the more complex rotenoid, rotenone. Rotenone was synthesised by the initial assembly of a chiral (-)-(R)-2-isopropenyl-2,3-dihydrobenzofuran-4-ol moiety, asymmetrically accessible using a stereoselective Pd π-allyl mediated cyclisation of (E)-4-(2,6-dihydroxyphenyl)-2-methylbut-2-enyl methyl carbonate. Having constructed the dihydrobenzofuran in an enantiomeric excess of 94.8%, the chromene part of rotenone could then be synthesised. To this end, the LDA mediated coupling reaction of the formylated dihydrobenzofuran and 1,2-dimethoxy-4-(prop-2-ynyloxy)benzene, gave a secondary alcohol which was subsequently oxidised to the corresponding alkynone, (-)-(R)-(6,7-dimethoxy-2H-chromen-4-yl)(4-methoxy-2-isopropenyl-2,3-dihydrobenzofuran-5-yl)methanone. A 6-endo-hydroarylation reaction was employed as a mild strategy to construct the chromene moiety, (-)-(R)-(6,7-dimethoxy-2H-chromen-4-yl)(4-methoxy-2-isopropenyl-2,3-dihydrobenzofuran-5-yl)methanone. Finally, a deprotection and a base-catalysed intramolecular oxo-Michael addition concluded the first stereoselective synthesis of rotenone in 17 steps and an overall yield of 0.02%

The purpose of this project was to investigate whether methodology developed in these laboratories for preparing 5/6 and 6/6 azabicyclic systems with bridged head nitrogen can be extended to 7/6, 8/6, 9/6 and 13/6 azabicyclic systems. The methodology entails the use of enaminones as central to the formation of the azabicyclic systems. The synthetic route adopted began with the Beckmann rearrangement reaction and/or the Schmidt reaction of cyclic ketones to make lactams, which were then thionated by Curphy or Brillon procedures. The Michael reaction of NH thiolactams with tert-butyl acrylate was followed by Eschenmoser sulfide contraction to afford the enaminones 132 which were utilised in the ring-closing step. This involved hydrolysis of the tert-butyl ester and cyclisation via a mixed anhydride. Ethyl 7-oxo-1,2,3,5,6,7-hexahydroindolizine-8-carboxylate 170b, 1-(4- nitrobenzoyl)-3,4,6,7,8,9-hexahydroquinolizin-2-one 172a, 1-benzoyl- 3,4,7,8,9,10-hexahydropyrido[1,2-a]azepin-2(6H)-one 173d, 1-(4-nitrobenzoyl)- 3,4,6,7,8,9,10,11-octahydropyrido[1,2-a]azocin-2-one 174a, and 1-(4- nitrobenzoyl)-3,4,7,8,9,10,11,12,13,14,17,16-dodecahydropyrido[1,2-a]azacyclotridecin- 2(6H)-one 176a were synthesised in good yields, but yields of 8-(4- nitrobenzoyl)-2,3,5,6-tetrahydroindolizin-7(1H)-one 171a and 1-(4-nitrobenzoyl)- 3,4,7,8,9,10,11,12-octahydropyrido[1,2-a]azonin-2(6H)-one 175a were not satisfactory. In a much shorter synthetic route that involves enaminone chemistry as well, NH vinylogous amides were synthesised by the Eschenmoser sulfide contraction and used in the aza-annulation reaction with acryloyl chloride. Structural isomers (to compounds mentioned above) 8-(4-nitrobenzoyl)-2,3,6,7-tetrahydroindolizin- 5(1H)-one 178a, 1-(4-nitrobenzoyl)-2,3,7,8,9,10-hexahydropyrido[1,2-a]azepin- 4(6H)-one 180a, 1-benzoyl-2,3,7,8,9,10-hexahydropyrido[1,2-a]azepin-4(6H)-one 180b, 1-(4-nitrobenzoyl)-2,3,6,7,8,9,10,11-octahydropyrido[1,2-a]azocin-4-one 181a, 1-(4-nitrobenzoyl)-2,3,7,8,9,10,11,12-octahydropyrido[1,2-a]azonin-4(6H)- one 182a and 1-(4-nitrobenzoyl)-2,6,7,8,9,10,11,12,13,14,15,16- dodecahydropyrido[1,2-a]azacyclo-tridecin-4(3H)-one 183a were synthesised in good yields. 1-(4-Nitrobenzoyl)-2,3,6,7,8,9-hexahydroquinolizin-4-one 179a was obtained in low yield, and apparently as two conformational isomers.

MSc, School of Chemistry, Faculty of Science, University of the Witwatersrand, 2011 / In this work, a detailed study of the evaluation of gold-based catalysts supported on manganese oxides for the oxidation of volatile organic compounds (VOCs) has been undertaken. Model catalysts were prepared by deposition-precipitation methods to establish the effect of the support on the catalytic activity of the gold catalysts. The catalysts were characterised by X-ray diffraction, transmission electron microscopy, N2–physisorption measurements and temperature programmed reduction techniques. The activity of the catalysts for VOC oxidation reactions were tested in a continuous flow fix bed glass reactor. The products were analysed by GC/TCD and GC/FID. The catalysts Au/TiO2, Au/Al2O3, Au/ZnO and Au/MnO2 were used for the VOC oxidation reaction. 2-propanol, 2-butanol and toluene were used as VOCs for the study. These were chosen because they are important indoor pollutants given their wide laboratory use and high volatility. Toluene was found to be the most difficult to oxidise, followed by 2-propanol. The effect of calcination temperature and preparation procedure was evaluated for the gold/manganese oxide catalysts. Au/b-MnO2 catalysts prepared by deposition-precipitation showed some catalytic performance which was less than the performance shown by Au/MnOx, prepared by co-precipitation. g-MnO2 proved to be more efficient in the oxidation of 2-propanol than pyrosulite phase MnO2. The addition of gold to any metal oxide support was found to enhance the oxidation of VOCs. Gold-based catalysts were more active than the Ce/MnO2 catalyst. Catalytic tests showed that Au/CeO2 was the superior catalyst for the total oxidation of toluene, 2-propanol and 2-butanol. Ceria is a highly reducible oxide and the formation of gold–ceria interactions produced an even more easily reduced material. University of the Witwatersrand, Johannesburg ii

A dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Master of Science. January 1996. / Aspects of the literature of the ant venom alkaloid monomorine I and its stereoisomers were reviewed. Racemic 5-butyl-2-pyrrolidinone was synthesised in two steps from methyl acrylate and 1-nitropentane, A thionation step yielded 5-butylpyrrolidine-2-thione. The Michael addition reaction between 5-butylpyrrolidine-2-thione and ethyl crotonate proceeded with difficulty to form a separable mixture of diastereomers of 5-butyl-l-(2-ethoxycarbonyl-l-methylethyl) pyrrolidine-2-thione. [Abbreviated Abstract. Open document to view full version] / AC2017

This thesis describes the application of the Sonogashira coupling reaction to access a variety of 5-and 7-azaindoles derivatives. The background chapter paints a picture about the importance of indole-containing compounds and azaindole-containing compounds. In this first chapter, discovery, synthesis, properties and reactivity of indole and azaindoles were explained.

The synthesis of alkaloids from enaminones has been used extensively in the University of the Witwatersrand’s organic chemistry laboratories. In this thesis enaminone precursors are one of the main ways of accessing lamellarin analogues. The lamellarin alkaloids are an important family of marine alkaloids, owing to their vast biological properties. A brief background to marine alkaloids and their general potential is given, followed by a review of lamellarin alkaloids, their structural and biological properties and some of the major syntheses carried out over the past few years. Two novel features form the basis of the synthetic methods described in the thesis. The first is an approach to forming the lamellarin alkaloids from enaminone precursors, which are prepared through the Eschenmoser sulphide contraction. The second method uses a novel pyrrole formation, which was initially conceptualized by Garreth L. Morgans in his PhD thesis (2008). The main target of the investigation was lamellarin G trimethyl ether. In Chapter 3, the syntheses of a range of mono-, di- and tetra-substituted phenacyl halides are discussed. The phenacyl halides were used in the preparation of various enaminone precursors. The tetrasubstituted phenacyl halide 2-bromo-1-(2-hydroxy-4,5-dimethoxyphenyl)ethanone 3.17 is required for the synthesis of our target lamellarin G trimethyl ether. The phenacyl halides are important in both the model synthesis described in Chapter 4 and the synthesis toward lamellarins in Chapter 5. Chapter 4 deals mainly with the synthesis of pyrrolizine systems. Methodology is described for the preparation of a variety of enaminones, pyrroles and tetracyclic lamellarin analogues. The closest pyrrolizine system to lamellarin G trimethyl ether, 11-(3,4-dimethoxyphenyl)-2,3-dimethoxy-9,10-dihydrochromeno[4,3-b]pyrrolizin-6(8H)-one 4.52, was the final and most complex tetracyclic model structure analogous to lamellarin G trimethyl ether. Indolizine and pyrroloazepine adaptations were also demonstrated and tetracyclic systems 10,11-dihydro-8H-chromeno[3,2-a]indolizin-12(9H)-one 4.39 and 9,10,11,12-tetrahydrochromeno[3',2':3,4]pyrrolo[1,2-a]azepin-6(8H)-one 4.40 were successfully prepared, even though the pyrrole formed in an unexpected way. Finally in Chapter 5, the methodology established in the model study was used in the attempted synthesis of lamellarin G trimethyl ether. A second method was also investigated. Thus, various N-alkylated and N-H enaminones were successfully synthesized, from which novel and unexpected pyrrole-containing products 8-(3,4-dimethoxyphenyl)-2,3-dimethoxy-5H-chromeno[3',2':3,4]pyrrolo[2,1]isoquinolin-14(6H)-one 5.28 and (3-ethoxy-8,9-dimethoxy-2-phenyl-5,6-dihydropyrrolo[2,1-a]isoquinolin-1-yl)(phenyl)methanone 5.37 were formed, even though our desired product lamellarin G trimethyl ether could not be attained from either method.

A dissertation submitted to the Faculty of Science for the degree of Master of Science University of the Witwatersrand, Johannesburg / It is well known that chlorinated organic compounds behave as highly toxic substances in the environment. Catalytic hydrodechlorination .... one of the more convenient approaches used to treat chlorinated organic substances with the aim of obtaining compounds with lower or null toxiciy. Further, the selective cleavage of the C-Cl bond plays a key role in processes related to the manufacture of fine chemicals. These reactions can be performed over noble-metal catalysts, either in the gas or liquid phase. (Abbreviation abstract) / Andrew Chakane 2018

by Lun Kue Sun. / Includes bibliographical references / Thesis (M.Ph.)--Chinese University of Hong Kong, 1986

Pang Sik Wing. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1979. / Bibliography: leaves 70-73. / Acknowledgement --- p.i / Abstract --- p.ii / Chapter Section I --- Introduction -- Annulenes, azaannulenes, bridged annulenes, and bridged azaannulenes --- p.1 / Chapter Section II --- Synthetic Plans --- p.19 / Chapter Section III --- Results and Discussions --- p.26 / Chapter Section IV --- Experimental --- p.51 / Bibliography --- p.70 / List of Spectra