The Asymmetric Total Synthesis Of Natural Product Isocurcumenol

This thesis aimed at the study on the total synthesis of guaiane-type natural product sesquiterpenoid Isocurcumenol.The main content was divided into the following two chapters :In the first chapter,the research status of asymmetric catalytic metal carbene transformations was reviewed.We briefly summarized the chiral catalysts for metal carbene transformations and introduced the applications of metal carbene transformations in organic synthesis,such as asymmetric insertion reactions,asymmetric cyclopropanation reactions,asymmetric ylide reactions,and so on.Among these,carbene carbonyl ylide cycloaddition cascade(CCCC)reaction was the most widely used in the synthetic world.These oxygen-containing polycyclic systems formed by this reaction are conspicuous structural units in many naturally occurring compounds,and have received extensive attentions from pharmaceutical chemists.In the second chapter,the structural characteristics of Isocurcumenol were briefly introduced;and the total synthesis study of Isocurcumenol was carried out.The precursor compound of Isocurcumenol 75 was obtained through 17 steps using readily available 3-butyn-1-ol as starting material.The key steps of this synthetic strategy includs: introduction of chiral methyl group in ?-position of carbonyl group by Evans asymmetric alkylation reaction;rapid prolongation of carbon chain by reaction of Weinreb amide 53 with Normant's Grignard reagent 87;the construction of [5,7]oxatricycle ketone by CCCC reaction of compound 56.Futuremore,We put emphasis on the preparation of diazocarbonyl compound 56;the asymmetric CCCC reaction catalyzed by chiral Rhodium catalysts and the reductive ring-opening of the oxygen bridge to generate hemiketal.And it provides the constructive suggestion for the total synthesis of guaiane sesquiterpenoid natural products.