The investigation has been focussed on the synthesis and characterisation of camphor-derived chiral auxiliaries that incorporate two camphor skeletons and an evaluation of their stereodirecting potential in ester α-benzylation reactions. Two regioisomeric camphorquinone-derived monoketals were synthesised and identified by 1D- and 2D-NMR, and X-ray crystallography. The stereo-directing potential of the alcohols that resulted from reduction of these ketones as chiral auxiliaries in the alkylation of carboxylate ester derivatives has been studied. The diastereoselectivities shown by NMR spectroscopy range from 14- 30 % d.e. for (1R,2 S, 3R) -2 ,2-[ (1R, 2 S, 3R) -bornane-2,3-dioxy] - bornan-3-ol and 68-74 % d.e. for (1R, 2S ,3R) -3 ,3-[ (1R, 2S ,3R) - bornane-2, 3 -dioxy]bornan-2-ol with selectivities that correlate with the size of the alkyl group in the ester moiety. Trapping of the enolates generated from (1R, 2S ,3R)-2, 2 -[(1R,2 S, 3R) -bornane- 2,3-dioxy]bornan-3-yl propanoate afforded both E- and Z-silyl ketene acetal derivatives in the ratio of 64:36 confirming the formation of both possible enolate structures during enolization. Chiral auxiliaries containing a hemiaminal ether blocking group as well as two chiral alcohols containing monothio-ketal blocking groups have also been synthesised. α-Benzylation of their corresponding propanoate esters afforded the alkylated product with disappointingly low diastereos electivities. Asymmetric reduction of α-keto esters attached to (1R, 2 S, 3R) - 2,2- [ (1R,2 S, 3R) -bornane-2, 3 -dioxy]bornan-3-ol and (1R, 2S ,3R) - 3,3- [ (1R,2 S, 3R) -bornane-2, 3 -dioxy]bornan-2-ol with metal hydrides proceeded with selectivities of up to 30 % d.e. Modelling of the keto ester derivatives at DFT levels provided useful insights into possible conformations adopted by the two α-keto esters and hence the preferred face of attack by metal hydride during reduction.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:nmmu/vital:10372 |
| Date | January 2008 |
| Creators | Skiti-Mama, Neliswa |
| Publisher | Nelson Mandela Metropolitan University, Faculty of Science |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis, Doctoral, PhD |
| Format | viii, 206 leaves, pdf |
| Rights | Nelson Mandela Metropolitan University |
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