Studies On Palladium-Catalyzed Selective Cleavage Of C-C ? Bonds Of Cyclopropenes And The Follow-up Transformations

As a kind of inert chemical bond widely existing in various organic compounds,C-C ?bond has the characteristics of thermodynamic stability and kinetic inertia.Therefore,the reactivity of C-C ? bond is very low under most conventional reaction conditions,and it is difficult to participate in the related reaction process.If such a nonpolar C-C ? bond can be selectively cut off and subsequently react with other reagents,not only the molecular carbon skeleton can be reconstructed,but also two different functional groups can be introduced at the same time,so as to realize the one-step construction of molecules or multi-functionalized products that are difficult to be efficiently synthesized by traditional methods from simple starting materials.The so-called "cut and sew" reaction mode endows the synthetic strategy with more flexibility and lays an important foundation for the synthesis and screening of bioactive drug-like molecular frameworks.Cyclopropene is the smallest unsaturated cyclic compound known at present,and its structure widely exists in natural products such as fatty acids.Thanks to its high ring strain and reactivity,the ring-opening and ring-retention reactions of cyclopropenes have been widely applied in the field of late modification of drug-like molecular framework and total synthesis of natural products.As a ?-metallophilic substrate,cyclopropene can undergo various transformations such as carbon metallization,hydrogen metallization,C-C bond activation and metal carbene formation under the action of transition metals.The extremely high ring strain of cyclopropene can provide an important driving force to facilitate the cleavage of C-C ? bond.Thus,cyclopropene has been an ideal candidate to realize metal-catalyzed C-C ? bond cleavage and the follow-up transformations.However,precisely controlling the selective cleavage of C-C ? bond in cyclopropene is challenging because of its high reactivity.The presented paper focused on the challenging project that transition metal catalyzed selective cleavage of C-C ? bonds of cyclopropenes and the follow-up transformations.The bifunctionalization and cycloaddition reactions of selective cleavage of the C-C ? bonds in cyclopropenes have been realized through two strategies,that is,?-carbon elimination and C-C activation.The main work is as follows:(1)Palladium-catalyzed selective alkynylallylation of the C–C ? bonds of cyclopropenesIn the field of metal-catalyzed dicarbofunctionalization of C-C bond,dicarbofunctionalization of C-C ? bond has been widely studied,but the selective dicarbofunctionalization of C-C ? bond is rarely reported.In this part(Chapter 2),palladium-catalyzed high regioselective and stereoselective alkynylallylation of the C–C ? bonds of cyclopropenes was achieved by using1,1-dicyanocyclopropenes and allyl propiolates for the first time.The results indicated that the reaction exhibited a wide range of substrates and good functional group tolerance.A series of1,5-diene-7-ynes can be prepared in good to excellent yields.Under the condition of reducing the loading of the catalyst,the catalytic products can be prepared in gram scale with a TON value of 390 by increasing the concentration of the reaction system and prolonging the reaction time.The catalytic products can be further transformed into phenanthrenes substituted with various functional groups,carboxylic acid and terminal alkyne.Moreover,a reasonable reaction mechanism was proposed through mechanism experiments and density functional theory(DFT)calculation.It was found that the process involving the selective insertion of C-Pd bond of the ambident palladium species into the double bond of the cyclopropenes,and the subsequent non-classical ?-carbon elimination promoted by1,4-palladium migration,took place in the reaction.In addition,the natural population analysis(NPA)charge evaluation was performed to further analyze the ? bond selectivity of the employed cyclopropenes.The results indicated that the selectivity of ? bond might be positively correlated with the difference of the NPA charges at C2 and C3 of the cyclopropenes.This reaction provides a method for the synthesis of drug molecules involving tetra-substituted ethylene skeleton in an atom-and step-economical manner.(2)Palladium-catalyzed [3+2] cycloaddition of cyclopropenes with allenesA few reports on the metal-catalyzed cycloaddition of cyclopropenes illustrated that the two carbon units employed in the reaction were concentrated on alkynes,alkynamides and other compounds containing triple bond.Therefore,finding suitable catalytic systems to precisely control the selective cleavage of C-C ? bond and other types of two carbon units matching with the reactivity of cyclopropenes will be important challenges to realize the related transformations and beneficial to enrich the structural types of catalytic products.In this part(Chapter 3),1,1-dicyanocyclopropenes and 1-substituted allenes or1,1-disubstituted allenes were employed to achieve palladium-catalyzed [3+2] cycloaddition reaction of cyclopropenes with allenes.The results indicated that a series of polysubstituted methylene cyclopentenes can be obtained with high regioselectivity and ?-bond selectivity by using tetratriphenylphosphine palladium as the catalyst,and the reaction also showed a wide range of substrates and excellent functional group tolerance.Moreover,the catalytic product can be further epoxidated to spirocyclic compound by taking advantage of the methylene active site.Then the possible reaction mechanism was preliminarily proposed through the mechanism experiment.It was inferred that the four-membered intermediates might form during the reaction process and the subsequent migration insertion of allenes in a high chemoselectivity manner are critical for the success of the reaction.In addition,the asymmetric cycloaddition of cyclopropenes with allenes was preliminarily studied,and the catalytic products were obtained in 85% yield and 87:13 er value.In this reaction,the allenes were used as two carbon units for the first time to go through [3+2] cycloaddition with cyclopropenes,and the reaction provides an atomic-and step-economical approach for the preparation of natural products and drug-like frameworks containing the structure of cyclopentene.