Study On Lewis Acid-Catalyzed 1,3-Dipolar Cycloaddition Reactions

1,3-Dipolar cycloaddition reaction is a classic reaction which is widely used for synthesis of natural products and biologically active compounds.We expect to develop new cycloaddition reactions,such as[3 + 3],[6 + 3],[8 + 3]and double[3 + 2]cycloaddition to access heterocyclic compounds.On the basis of Lewis acid-catalyzed cycloaddition of azomethine ylides with alkenes and fulvenes,we developed copper/ferrocenyl P,N ligand-catalyzed asymmetric[3 + 3]cycloaddition of a-iminoesters with N,N'-azomethine imines.The reactions proceeded smoothly under mild conditions,affording heterocycles in moderate to high yields with excellent diastereo-and enantioselectivies.Under acidic conditions,an epimerization of the products occurred to give their diastereomers.The treatment of product with LiBH4 afforded a bicyclic heterocyclic compound.Then we reported the first metal-catalyzed[6+3]cycloaddition of tropone with azomethine ylides and its asymmetric variant.The procedures are operationally simple and the catalysts are cheap and readily accessible,thus providing a practical approach to piperidine-fused bicyclic heterocycles.The present asymmetric reaction could be performed on the gram scale.The conjugated diene motif in the product was reduced via Pd/C-catalyzed hydrogeanation.Alternatively,treatment of the product with NaBH4 gave the azabicyclo[4.3.1]deca-2,4-dien-10-ol derivative.In situ generated 1,3-dipole from cyclopropane and aziridine in the presence of Lewis acid can participate in cycloaddition reactions.The Sc(OTf)3-catalyzed diastereoselective[3 + 3]cycloaddition of phthalazinium dicyanomethanides with cyclopropane 1,1-diesters proceeded smoothly under mild reaction conditions,affordi'ng a variety of 3,4-dihydro-1H-pyrido[2,1-a]phthalazine derivatives in high yields with excellent diastereoselectivities.The present reaction is quite robust,allowing it to be performed on the gram scale.Through treatment of the product with H2/Pd/C,one of two cyano groups was reduced to an amine.On the other hand,by treatment of the product with NaBH4,one of two cyano groups was transformed into the MeO group.The Ni-catalyzed[8 + 3]cycloaddition of tropone with 2-aryl-N-tosylaziridines have been developed.The reaction can be performed on the gram scale.Three double bonds in the product was reduced to cycloheptindole derivative with H2/Pd/C.In addition,the 1,3-dipolar cycloaddition of allenoates with two nitrilimine precursors proceeded smoothly with the use of base,affording spirocyclic compounds in high yields and excellent diastereoselectivities.