Palladium-catalyzed Oxidation Of Spirovinylcyclopropanes Ring-opening Formal [3+2]-cycloaddition To Construct Polycyclic Spirooxindoles

Spirooxindole frameworks are widely existed in natural products and pharmaceuticals.Some of spirooxindoles have been proved to possess various biological activities.Thus,it is of significance to develop new strategies for the construction of spirooxindole derivatives.In this thesis,the newly developed spirovinylcyclopropyl oxindole derivatives were used for the diatereoselective synthesis of bispirooxindoles through palladium-catalyzed ring-opening[3+2]-cycloaddition.Moreover,a various of chiral phosphine ligands were evaluated for the asymmetric construction of bispirooxindole derivatives.The body of reaserch work in this paper is divided into four parts as follows:In the first chapter,the structure and properties of spirooxindole and cyclopropane derivatives are introduced.The synthetic strategies of spirooxindoles and the ring-opening[3+n]-cycloaddition of donor-receptor cyclopropanes for the construction of five-membered cycle and five-membered heterocyclic compounds were reviewed.The significance and research ideas of this paper are illustrated on this basis of the above-mentioined studiesPIn the second chapter,the strategy of[3+2]-cycloaddition of spirovinyl cy cl opropyl oxindole derivatives and isatin derivatives,condition optimized process,the tolerance of substrates and exploring of asymmetric[3+2]-cycloaddition reaction are introduced.After the optimized reaction conditions established,the optimal conditions:Pd(OAc)2/Xantphos as catalyst,tetrahydrofuran as solvent,the reaction was carried out at room temperature.The bispirooxindole derivatives were successful delivered in good to excellent yields(up to 82%)with excellent diastereoselectivities(>20:1).Besides,the proposed mechanism and the asymmetric synthesis of bispirooxindoles catalyzed by chiral phosphine ligands were also invastigated.In the third part,the synthesis steps of the starting materials and chiral ligands as well as desired products and instruments were described.Furthermore,The synthesized compounds were subjected to characterization by NMR spectra,Fourier transformed infrared spectroscopy(FT-IR)and High resolution mass spectroscopy(HRMS),etc.The conclusion part has summarized the research contents of this thesis.In this paper,a series of bispirooxindole derivatives were synthesized via palladium-catalyzed ring-opening cyclizationin good to excellent yields with excellent diastereoselective.The asymmetric results revealed that the high enantioselective synthesis of bispirooxindole derivatives remains a difficult problem to overcome.