Asymmetric Dearomatiye [3+2] Cycloaddition Of 2-Nitrobenzofurans With Morita-Baylis-Hillman Carbonates

Tricyclic hydrogenated benzofuran structures are the core backbones of many natural products,bioactive molecules and drugs.Experiments have proved that compounds containing a tricyclic hydrogenated benzofuran structure have anti-leukemia,anti-tumor,anti-inflammatory and other biological activities.One of these compounds,galantamine,has been successfully used in the treatment of polio,myasthenia gravis and other diseases.Therefore,it is of great significance to develop an effective construction route for such compounds.Catalytic asymmetric dearomatization(CADA)reactions are a powerful tool for the enantioselective construction of polycyclic three-dimensional molecules from easily available aromatic compounds,so it has attracted much attention.The CADA reactions of electron-rich heteroarenes(such as indoles,pyrroles,furans,etc.)have been widely developed.However,electron-deficient nitro-heteroarenes are challenging substrates for CADA reactions.In recent years,our group has been exploring the dearomatization reactions of heteroarenes,and in 2019 reported the Cu(I)-catalyzed asymmetric dearomative 1,3-dipolar cycloaddition of 2-nitrobenzofurans with imine ylides for the synthesis of pyrrole-fused hydrobenzofurans.Based on this,we developed the asymmetric dearomative [3+2] cycloaddition reaction of 2-nitro-benzofurans with MBH carbonates.The reaction is catalyzed by organocatalyst,various cyclopentannulated hydrobenzofurans with three continuous stereocenters,highly functionalized were obtained in good to excellent yields,excellent regioselectivity,excellent diastereoselectivities and enantioselectivities.The reaction conditions are mild and simple,and the substrates are universal.It can carry out scale-up experiments,and the products can be further functionalized.Furthermore,the asymmetric dearomative [3+2] cycloaddition reaction of 2-nitrobenzofuran and allenoate can obtain product with moderate enantioselectivity,related research work is continuing.The structures of the new compounds were characterized by NMR,high-resolution mass spectrometry and other detection instruments.The absolute configuration of the dearomatization products were determined by X-ray single crystal diffraction,and the absolute configuration of the derivative was indirectly determined by two-dimensional spectrum.