Asymmetric Construction Of Chiral Nitrogen Heterocycles Via Copper-Catalyzed 1,3-dipolar Cycloaddition

Chiral nitrogen heterocycles exhibit great value in pharmaceuticals,chemical research,and other fields.Furthermore,catalytic asymmetric 1,3-dipolar cycloaddition has arguably been one of the most ideal and powerful synthetic strategies for the construction of chiral nitrogen heterocycles.This dissertation mainly focuses on the asymmetric construction of chiral nitrogen heterocycles via copper-catalyzed 1,3-dipolar cycloaddition,including three aspects as follows:1)the asymmetric construction of highly substituted tetrahydro-?-carbolines via Cu-catalyzed 1,3-dipolar[3+3]cycloaddition;2)the asymmetric synthesis of dispiropyrrolidines via Cu-catalyzed 1,3-dipolar[3+2]cycloaddition;additionally,the development of an efficient route to 2,3'-dispiropyrrolidines;3)facile access to spirocyclic pyrrolidine-thia(oxa)zolidinediones via Cu-catalyzed asymmetric 1,3-dipolar[3+2]cycloaddition.In the first part,catalytic asymmetric[3+3]cycloaddition of azomethine ylides with 2-indolylnitroethylenes was described,providing an efficient method to highly substituted tetrahydro-y-carbolines.In the the presence of CuPF6/Ph-Phosferrox complex,tranditional[3+2]cycloaddition was suppressed obviously,and an array of chiral tetrahydro-y-carboline compounds was generally obtained in high yields with high chemoselectivities and excellent levels of stereoselectivities.Moreover,a stepwise mechanism was proposed according to the control experiments.In the second part,a highly stereoselective[3+2]cycloaddition of azomethine ylides to itaconic amide derivatives was developed,applying the Cu(OAc)2/1,3-dihydroimidazol pyridine-based N,O-ligands catalytic systems in our laboratory.The dispiropyrrolidine skeleton was builded in high-efficiency through the reduction of[3+2]cycloadduct.In addition,a novel route to chiral 2,3'-dispiropyrrolidine compounds via Michael addition of cyclic azomethine ylide to nitroalkenes was developed.In the third part,a highly efficient asymmetric[3+2]cycloaddition of azomethine ylides to 5-alkylidene thiazolidine-2,4-diones was discribed,affording structurally novel spirocyclic pyrrolidinethiazolidinedione compounds.Excellent levels of diastereo-and enantioselectivities were obtained in the presence of CuBF4/1,3-dihydroimidazolpyridine-based N,O-ligands catalytic systems.Furthermore,5-alkylidene oxazolidine-2,4-diones as dipolarophiles were also suitable to this transformation,providing spirocyclic pyrrolidine-oxazolidinediones in high stereoselectivities.