Synthesis Of Chiral Aza-[n.2.1] Skeleton Derivatives

In this paper,the synthesis of chiral bridged aza-[n.2.1] skeletons is mainly studied.Under the induction of chiral auxiliary group,the separable chiral bridged aza-[n.2.1] skeletons are efficiently constructed through intramolecular [3+2] cycloaddition reaction of DA-cyclopropane catalyzed by Lewis acid.Removal of auxiliary groups and derivation of chiral aza-[3.2.1] skeleton compounds are explored.The full text is divided into two chapters:In chapter 1,the research progress including cycloaddition reactions of DA-cyclopropane and the synthesis of nitrogen heterocyclic skeleton is reviewed.Cycloaddition reactions of DA-cyclopropane with imine,carbonyl,thiocarbonyl and olefin are described,and the construction methods of the nitrogen heterocyclic skeleton are summarized from the perspectives of aza-bridged ring and aza-fused ring skeletons in detail.In chapter 2,the synthesis,removal of auxiliary groups and derivation conversion of chiral bridged aza-[n.2.1] skeleton are introduced.The intramolecular [3+2] cross cycloaddition reaction between cyclopropane and chiral sulfinylimines catalyzed by Lewis acid is used to synthesize the separable chiral bridged aza-[n.2.1] skeletons through the induction of chiral auxiliary group.This synthesis can be performed in gram-scale with high yield.In addition,the auxiliary group sulfinyl can be removed,and we have synthesized four chiral bridged aza-[3.2.1] skeleton enantiomers.It is worth noting that the configuration of the chiral bridged aza-[3.2.1] skeleton remains unchanged during these transformations.In summary,intramolecular [3+2] cross cycloaddition reaction of cyclopropane and chiral sulfinylimine catalyzed by Lewis acid is applied to synthesize chiral bridged aza-[n.2.1] skeleton and its derivatives,which is of great significance for the screening of active drugs and the absolute configuration control of the aza-bridged ring skeleton.