Palladium Catalyzed [5 + 1] Carbonylation Of Vinyl Aziridines

Vinyl aziridines are an important chemical synthesis block,which contains olefins and aziridine strained rings in their structures,and were widely used in the synthesis of nitrogen-containing,especially nitrogen-containing heterocyclic compounds.Nitrogen containing heterocyclic skeletons widely exist in bioactive natural products,pesticides and drug molecules,such as six-membered piperidine analgesics,pyridine pesticides and four membered ringβ-lactam drugs,etc.In the past few decades,the cycloaddition reactions of vinyl aziridines have used aziridine as the reaction module and take it as a three-membered synthon to generate[3+1],[3+2],[3+3],[3+4]cycloaddition reactions,and the use of vinyl azirides as a five-membered synthon for[5+2]cycloaddition reaction,however,it is rarely studied for[5+1]carbonylation reaction as a five-membered synthon.Therefore,this paper is devoted to studying of the[5+1]carbonylation reaction of one-membered synthons with vinyl aziridines.The first experimentally explored one-membered synthon is carbon monoxide,after literature research,it was found that carbon monoxide can be used as a carbonyl source in the presence of catalyst for the carbonylation reaction with vinyl aziridines.Therefore,the palladium-catalyzed[5+1]carbonylation reaction of vinyl aziridines with carbon monoxide was experimentally explored in this paper.This protocol provided an efficient and practical method for solvent controlled divergent synthesis ofα,β-andβ,γ-unsaturatedδ-lactams.Due to carbon monoxide is toxic and expensive,after completing the above work,try to replace carbon monoxide with other greener and safe reagents to study the[5+1]carbonylation reaction.According to the literature,divalent palladium can form[Pd ^II]=CF₂ with difluorocarbene,which can be used as a carbonyl source in the presence of water.As a precursor of difluorocarbene,sodium chlorodifluoroacetate is stable,safe and inexperience,so it was explored as a one-membered synthon for study[5+1]carbonylation reaction.Palladium catalyzed[5+1]carbonylation of vinyl aziridines and vinyl epoxides with sodium chlorodifluoroacetate was investigated experimentally,it has the characteristics of safe reaction,mild conditions and wide substrates range.On the basis of literature review and subject research,this paper mainly completes the following work:（1）The[5+1]carbonylation of vinyl aziridines e with carbon monoxide;（2）The[5+1]carbonylation of vinyl aziridines and vinyl epoxides with sodium chlorodifluoroacetate;（3）Based on the research on the[5+1]carbonylation reaction of vinyl aziridines with carbon monoxide,32 compounds were synthesized,including 28 new compounds,17β,γ-unsaturatedδ-lactams and 11α,β-unsaturated δ-lactams.The structures of these compounds were confirmed by ¹H NMR,¹³C NMR and HRMS;（4）Based on the research on the[5+1]carbonylation reaction of vinyl aziridines and vinyl epoxides with sodium chlorodifluoroacetate,30 compounds were synthesized,including 16α,β-unsaturatedδ-lactam compounds and 14α,β-unsaturatedδ-lactone compounds was synthesized.These structures were confirmed by ¹H NMR,¹³C NMR and HRMS;To sum up,based on the[5+1]carbonylation reaction between vinyl aziridines and vinyl epoxides,this paper designed and synthesized 17α,β-unsaturatedδ-lactams,17β,γ-unsaturatedδ-lactams,14α,β-unsaturatedδ-lactones.The study on[5+1]carbonylation cycloaddition reaction of vinyl aziridines as a five membered synthon is supplemented,and the reaction characteristics of vinyl epoxides were explored accordingly,which provided a mild and economical synthesis method for the synthesis of six membered unsaturated lactams and lactones.