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.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:262319 |
| Date | January 1995 |
| Creators | Aboutayab, Karim |
| Publisher | University of Sussex |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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