Employing a chiral pool strategy, enantiospecific syntheses of di- and triquinanes have been accomplished. α-Campholenaldehyde 95, readily available from the abundantly available monoterpene α-pinene 94, has been utilised as the chiral starting material.
To begin with, enantiospecific synthesis of the diquinane 134 has been developed employing Nazarov cyclisation of the cross-conjugated dienone 132 as the key reaction (Scheme 37).71 Synthesis of the dienone 132 was accomplished by selenium dioxide mediated oxidation of the olefinic methyl group in α-campholenyl methyl ether 130, followed by further elaboration of the resultant aldehyde 131.
OMe P2O5 MsOH
The Nazarov cyclisation strategy has been further extended, as depicted in Scheme 38, for the synthesis of the triquinane enones 145 and 146 via the cross conjugated enone 144.71 The dienone 144 was obtained from the diquinane 136, which is readily available from campholenaldehyde 95 via an intramolecular rhodium carbenoid CH insertion reaction.
Of the three methyl groups in campholenaldehyde 95, the olefinic methyl group can easily be functionalised, for example, via allylic oxidation. However, the remaining two tertiary methyl groups are difficult to functionalise, and there is no report in the literature on the utility of these two gem dimethyl groups either for functionalisation or for further elaboration, and remained only as gem dimethyl group in the products. It was conceived that it could be possible to utilise the tertiary methyl carbon for the ring construction via an intramolecular rhodium carbenoid γ-CH insertion reaction. To test the hypothesis, campho¬lenaldehyde 95 was converted into the diazoketone 165. Treatment of the diazoketone 165 with a catalytic amount of rhodium acetate furnished the diquinane 166, via a highly regio-and stereoselective insertion of the intermediate rhodium carbenoid in the CH bond of the tertiary methyl group, which is located cis with respect to the diazoketone, Scheme 39.72
As an application of the Nazarov cyclisation mediated synthesis of the diquinane 134, enantiospecific synthesis of the analogues of capnellenes, ABC and ABD ring systems of aberraranes have been carried out. A methyl cuprate reaction on the enone 134 generated the key intermediate, the ketone 169. A ring-closing metathesis (RCM) based cyclo¬pentannulation has transformed the diquinane 169 into the analogue of capnellene 175, as well as the analogue 197 of the ABC ring system of aberrarane. On the other hand, a Wacker reaction-intramolecular aldol condensation based spirocyclohexannulation transformed the diquinane 169 into an analogue 201 of the ABD ring system of aberrarane, Scheme 40.73
Finally, degradation of the two additional carbon atoms present on the A-ring furnished the ABC and ABD ring systems 235 and 238 of aberrarane, Scheme 41.(For structural formula pl refer the abstract pdf file)
| Identifer | oai:union.ndltd.org:IISc/oai:etd.ncsi.iisc.ernet.in:2005/3159 |
| Date | January 2012 |
| Creators | Janardhan, Ghodke Neetu |
| Contributors | Srikrishna, A |
| Source Sets | India Institute of Science |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
| Relation | G25476 |
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