Lithium Iodide-promoted Intramolecular [3+2] Cycloaddition Of Aziridine And Epoxy With Electron-deficient Olefins

Bridged aza-and oxa-[n.2.1](n=3,4)skeletons,which have specific rigid structures,are frequently found in many natural products and biologically active molecules with great application value in chemistry,biology and medicine.They show good biological activities such as anti-tumor,anti-inflammatory,anti-depressant,anti-fungal and anti-virus,and play an extremely important role in the development of modern medicine and pesticides.The synthetic methodologies of these compounds with bridged skeletons have always been a research hotspot in synthetic organic chemistry.Especially in recent years,many chemists begin to search for the new,concise,efficient and selective synthetic methods towards bridged compounds with more and more complicated bridged natural products found.In this paper,we mainly introduce the methods for the efficient construction of bridged aza-and oxa-[n.2.1](n=3,4)skeletons by intramolecular formal[3+2]cycloaddition reaction.Firstly,we designed and synthesized a kind of substrates containing both aziridines and electron-deficient alkenes.We selected lithium iodide to react with such aziridines to initiate the tandem reactions.Lithium iodide first selectively attacked the side with less steric hindrance in the aziridine to provide ring-opening products,which underwent further intramolecular Michael addition reaction and S_N2substitution reaction to general the final products with bridged aza-[n.2.1](n=3,4)skeletons.The lithium iodide-promoted tandem cyclizations can be regarded as intramolecular formal[3+2]cycloaddition of aziridines with electron-deficient alkenes.In this intramolecular formal[3+2]cycloaddition,new C-C bond and C-N bond was formed.This intramolecular formal[3+2]cycloaddition is also used to synthesize the important intermediate of homoepiboxidine.Secondly,we designed and synthesized a kind of substrates containing both epoxides and electron-deficient alkenes.We selected lithium iodide to react with such epoxides to initiate the tandem reactions.Lithium iodide first selectively attacked the side with less steric hindrance in the epoxide to provide ring-opening products,which underwent further intramolecular Michael addition reaction and S_N2 substitution reaction to general the final products with bridged oxa-[n.2.1](n=3,4)skeletons.The lithium iodide-promoted tandem cyclizations can be regarded as intramolecular formal[3+2]cycloaddition of epoxides with electron-deficient alkenes.In this intramolecular formal[3+2]cycloaddition,new C-C bond and C-O bond was formed.The above methods have the advantages such as high bonding efficiency,mild reaction conditions,simple operation,high yields,good generality of the ring size in product,which behave good industrial development prospects.They provide a good choice for the efficient construction of bridged aza-and oxa-[n.2.1](n=3,4)skeletons.