Transition-Metal-Catalyzed Reactions Of Enynes To Construction And Functionalization Of Polycyclic Natural Products Skeletons

Polycyclic terpenoids with diverse biochemical properties exist widely in nature,and they are often effective ingredients in many medicines,fragrances and cosmetics.How to selectively modify the designated sites of terpenoid molecules,or efficiently construct the bridged or spiro polycyclic structure of them,has always been a research hotspot in forest chemical industry.In the paper,transition-metal-catalyzed reactions of enynes were used to synthesize polycyclic terpenes containing the skeletons of bicyclo[3.3.1]nonenes or 6/5/5 fused spirocycles,and modified some polycyclic natural products by fluorination or olefin functionalization.In the paper,a variety of bicyclo[3.3.1]nonenes and 6/5/5 fused spirocyclic terpenes containing different functional groups such as indolyl were successfully prepared by gold(I)-catalyzed cycloisomerization of ene-alkene-ynes in one step.In order to explore the potential value of this gold catalytic strategy,we performed gram-scale experiments and functional group conversion,and proposed a plausible mechanism of gold(I)-catalyzed sequential cyclization of ene-alkene-ynes.We believe this strategy will provide a brand new method for the futural preparation of complex polycyclic natural products or drugs.Organic fluorine chemistry is currently one of the hot research fields and the introduction of fluorine will significantly change the physiological properties of bioactive molecules.We combined transition-metal-catalyzed reaction with fluorination,and found that linear enyne esters may convert to 5-fluorocyclopentenone under the gold catalyst and fluorination reagent with onepot operation.We then proposed the mechanism of gold(I)-catalyzed cycloisomerization and electrophilic fluorination of enyne esters based on relevant literature and control experiments.The paper also developed a Markovnikov-selective hydroalkylation for unactivated olefins using the amide derivative of the natural alkaloid quinoline as directing group.Compared with the traditional reductive coupling,owing to the dual role of haloalkanes as a mild hydride and alkyl donor,the strategy avoids exogenous protic source or hydrosilane/base reagent,so it has a much wider range of functional group compatibility and already has been successfully applied to the ?-position selective alkylation of 1,2-disubstituted alkenes and remote olefins.We have also proposed the nickel catalyst circulation mechanism based on the radical clock experiment and deuterium labeling experiments.In order to explore its practical value,the research modified the structure of some forest-derived bioactive molecules,and successfully prepared several precursors of small molecule drugs,so to provide new ways for the modification or preparation of drugs.We expect our catalytic strategy to find significant utility in chemical synthesis and might be the example of the combination of forest chemical industry and organic chemistry.