Allylic substitution is an important procedure for carbon-carbon, carbon-nitrogen and carbon-oxygen bond formation, and palladium-mediated allylic substitution reactions have previously been employed in the synthesis of a range a physiologically active and natural products. 2,5-Dicarbon substituted 2,5-dihydrofurans have not to date been synthesised by palladium-mediated allylic substitution reactions. It was found in the first part of the work that allylic substitution reactions of 2,5-diacetoxy-2,5-dihydrofuran with a tertiary carbon nucleophile did not result in the desired mono-substitution product due to the elimination of acetic acid from the product, to form the aromatised furan derivative. In an attempt to differentiate between the two potential leaving groups on the dihydrofuran, one of the acetate groups was displaced in a palladium-mediated allylic substitution reaction. This approach was also intended to inhibit the aromatisation reaction. The desired product 2-acetoxy-5-phenoxy-2,5-dihydofuran was obtained. The palladium-mediated allylic substitution reactions of this product with a range of tertiary carbon nucleophiles provided the desired mono-substituted dihydrofuran products in good yield with minimal by-products being detected. The substitution of the phenoxy-leaving group with a carbon nucleophile, however, was not achieved under a range of reaction conditions. Other more electrondeficient phenol derivatives were used in the initial substitution reactions but due to time constraints the work could not be completed in the current study. This would hopefully have increased the leaving group ability of the phenoxy group and the desired disubstituted dihydrofuran would have been achieved, and this will be the subject of further work in this regard. Milder reaction conditions were applied to 2,5-diacetoxy-2,5-dihydrofuran in its reaction with a tertiary carbon nucleophile. The desired mono-substituted mono acetoxy products were obtained in reasonable yields when column chromatography was performed at –15 °C and the silica was neutralised with Et3N. These mono-acetoxy products were reacted with a range of tertiary carbon nucleophiles and the desired disubstituted dihydrofurans could be prepared in reasonable yields. One-pot reactions were investigated by using three equivalents of nucleophile and in most cases the desired symmetrical dihydrofuran was achieved. This result prompted the investigation into the synthesis of disubstituted dihydrofurans in a one-pot reaction by successive addition of two carbon nucleophiles with 2,5- diacetoxy-2,5-dihydrofuran. The disubstituted dihydrofurans were isolated in higher yields than the two-pot procedure and the complex purification procedure developed was not necessary. This study, therefore, allowed for the synthesis of a range of symmetrical and unsymmetrical dicarbon substituted dihydrofurans. This methodology will later be applied to the synthesis of a range of natural products. / Prof. D.B.G. Williams
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:uj/uj:6972 |
| Date | 09 May 2008 |
| Source Sets | South African National ETD Portal |
| Detected Language | English |
| Type | Thesis |
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