| In the view of chiral nitrogen-containing fused ring compounds take on a very important role in organic synthesis and drug discovery.In this paper,we have devoted to developing novel catalytic asymmetric 1,3-dipolar cycloadditions of azomethine ylides,providing convenient and efficient strategies for the synthesis of structurally novel chiral nitrogen-containing fused ring compounds,the research work contains the following three aspects:(1)Asymmetric synthesis of chiral pyrrolidine-fused benzo[b]thiophene derivatives via 1,3-dipolar cycloaddition of azomethine ylides;(2)Asymmetric desymmetrization of cyclopropenes for synthesis of chiral 3-azabicyclo[3.1.0]hexane derivatives involved transformations of azomethine ylides;(3)Asymmetric construction of chiral 1,3-diazabicyclo[3.1.0]hexane skeletons and kinetic resolution of 2H-azirines via 1,3-dipolar cycloaddition of azomethine ylides.In the first part,a highly efficient asymmetric 1,3-dipolar cycloaddition of azomethine ylides with benzo[b]thiophene 1,1-dioxides was developed,providing a series of chiral pyrrolidinefused benzo[b]thiophene derivatives with significant biological activities.With(S)-DTBMSegphos/Cu(MeCN)4BF4 complex as the catalytic system,the desired products were obtained in good yields(72-99%)with excellent diastereo-and enantioselectivities(up to 99%ee,up to>25:1 dr).The asymmetric synthesis of chiral pyrrolidine-fused benzo[b]thiophene derivatives with synthetic application value was realized for the first time.In the second part,we have developed a highly efficient asymmetric 1,3-dipolar cycloaddition of azomethine ylides with prochiral cyclopropenes using the strategy of desymmetrization.With(S,Sp)-Ph-Phosferrox/Cu(MeCN)4BF4 complex as the catalyst,a wide range of 3-azabicyclo[3.1.0]hexane derivatives bearing five contiguous stereogenic centers(containing two all-carbon quaternary stereogenic centers)were synthesized in high yields(8099%)and extremely excellent level of stereoselectivities(97-99%ee)under mild reaction conditions.Moreover,the cycloadduct was successfully converted to rigid GABA analogues.This synthetic method offers a convenient and efficient approach to structurally important fullysubstituted chiral 3-azabicyclo[3.1.0]hexane derivatives.In the third part,a highly efficient kinetic resolution of racemic 2H-azirines has been achieved by means of catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides.With(S,Sp)-Ph-Phosferrox/Cu(MeCN)4BF4 complex as the catalyst,the optically pure 2Hazirines were obtained in good recovery yields(up to 49%)and excellent enantioselectivities(94-99%ee)with the S factors up to 845.Notable,this protocol provided a bran-new approach to structurally novel chiral 1,3-diazabicyclo[3.1.0]hexane derivatives,with excellent enantioselectivities which up to 99%ee. |
