The work presented in this thesis is aimed at the total synthesis of 14,21-dehydrosecodine (1). This substance is an indole derivative with reactive substituents at position 2 (an acrylic ester segment) and 3 (a 1,6-dihydropyridine system). The stabilization of the latter involved the generation of chromium carbonyl complexes employing trisacetonitriletricarbonylchromium (0) as the reagent with appropriate synthetic indole derivatives. In order to develop the required methodology for the preparation of the above complexes, the initial experiments employed simple dihydropyridine systems. Thus, when N-methyl-3-ethyl pyridinium iodide (4_1) was treated with NaBH^ in a two-phase system (ether - water), N-methyl-3-ethyl-1,2-dihydropyridine (46_) was obtained. When this compound was treated with the above complexing agent a mixture (ratio 1:2) of (N-methyl-3-ethyl-l,2-dihydropyridine) tricarbonylchromium (0) (4_3) and (N-methyl-3-ethyl-l, 6-dihydropyridine) tricarbonylchromium (0) (4_4) was obtained. Thermal isomerization of this mixture in refluxing cyclo-hexane afforded a 1 : 1 ratio of (4_3) and (4_4) . Liberation of the organic ligand could be achieved by stirring (43) and/or (4_4) with pyridine. The above strategy was applied to the indole intermediate, N-(2-carbomethoxymethyltryptophyl)-3-ethylpyridinium per-chlorate (_36) but only a low yield (2%) of the desired chromium complexes was obtained. These results prompted a change in the original synthetic strategy and a new approach was initiated by other coworkers in this laboratory. Some studies with the novel system (4_6) were conducted as they relate to position of alkylation. It was shown that (46) undergoes reaction with benzyl bromide to afford the 5-substituted derivative. / Science, Faculty of / Chemistry, Department of / Graduate

The work in this thesis describes investigations into the development of a tandem radicallDiels-Alder reaction strategy for the construction of indole alkaloids. The synthesis of a key precursor, 2-[(4-methylphenyl)sulfonyl]indole, was investigated and involved two main· strategies: functionalisation of the indole ring using lithiation procedures and assembling the indole as a key step (chapter 2). A method based on the former strategy was deemed to be the most practical and delivered the desired product in moderate yields (35 - 45%). The viability of the first step of the proposed tandem radicallDiels-Alder strategy was investigated by examining the intramolecular addition of vinyl and aryl radicals to a sulfone substituted indole (chapter 3). These studies showed that the addition of sp2 centred radicals to substituted indoles was feasible (20 - 40%). A study using an acetylenic precursor also provided useful information about the relative rates of desulfonylation and radical addition to acetyleneS; de-sulfonylation is a competing process. An alternative tandem palladiumlDiels-Alder reaction was briefly examined, but was thwarted by capricious palladium catalysed cross coupling reactions. Further studies were carried out to extend the scope of the novel ipso substitution reaction (chapter 4). It was found that alkyl radical cyclisations proceed efficiently to give a new ~ethod for the synthesis of fused[1,2-a]indoles (30 - 84%). The feasibility of a related ipso substitution using phenylthio and phenylsulfinyl substituted indoles was also examined. It was found that these reactions are also successful, but proceed in reduced yields compared with the sulfones (24 - 51 %). These results could be attributed to the more favoured reaction of the electron rich carbon centred radical with the more electrophilic 1t bond. The thesis is concluded by a brief discussion of the mechanism of these cyclisations with the available experimental evidence supporting an addition! elimination pathway.

Thesis (Ph. D.)--University of Texas at Austin, 2007. / Vita. Includes bibliographical references.

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

No description available.

Thesis (Ph. D.)--University of Hong Kong, 1993.

Thesis (M. Phil.)--University of Hong Kong, 1990.

Thesis (M. Phil.)--University of Hong Kong, 1991.

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

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