Synthetic studies of taxol and asymmetric Diels-Alder reaction using Fischer carbene chemistry

This dissertation describes the study of the synthesis of Taxol skeleton. The key steps involved an intramolecular cycloaddition of (2+2) ketene and alkene generated by 1,6-enyne and chromium carbene complex and a Grob fragmentation reaction. Both reactions were very successful in generating an ABC ring intermediate. This approach afforded a 6, 8, 6-membered ring intermediate of taxol which could be further functionalized at C13 position for putting the side chain by a known procedure. The synthesis of the suitable enyne for use in the (2+2) cycloaddition reaction and chromium carbene complex containing a partially functionalized C ring by a Diels-Alder reaction approach were also achieved. Unfortunately, the methyl methoxy carbene complex with C-8 methyl on the C ring gave fairly amount of non-CO insertion product and therefore carbene complex with C ring but without C-8 methyl group will be needed. The alternative way is to tune the electronic factor on the carbene complex and thus affect the CO insertion step in the formative steps of ketene. The experiment showed that the MOM carbene complexes increase the CO insertion product as well as increasing the thermal product vs the kinetic product in the (2+2) reaction.;The exo-selective Diels-Alder reaction of chelate imidazolidinone carbene complex and the trans-piperylene gave lower exo/endo selectivity than the similar reaction of Danishefsky's diene. The concerted mechanism was supported by the X-ray crystallography and can explain the change of the selectivity when the two different dienes were used.;Benzannulation reaction of non-chiral chelate oxazolidinone chromium carbene complex and alkyne was studied in two different solvents. The terminal alkyne gives higher yield than the internal alkyne.