The Study On Amidphos/Ag(Ⅰ)-catalyzed [3+2] Cycloaddition And Construction Of The Core Structure Of Deethylibophyllidine

Deethylibophyllidine alkaloid,whose structural unit contains a highly substituted pyrrolidine skeleton,is a terpene indole alkaloid with important biological activity.In recent years,the synthesis of highly substituted five-membered nitrogen heterocycles has become a important issues.The asymmetric[3+2]cycloaddition reaction involving azomethine ylide is an efficient method for constructing these highly substitutedpyrrolidinederivatives.Inthisthesis,Amidphos/Ag（I）-catalyzed asymmetric[3+2]cycloaddition and the construction of the core structure of deethylibophyllidine alkaloid were investigated.1.Study on asymmetric[3+2]cycloaddition reactions catalyzed by cyclohexanediamine-derived Amidphos/Ag（I）:firstly,the II-1c/Ag₂O catalytic system derived from（1S,2S）-1,2-cyclohexanediamine was studied.It can effectively catalyze the asymmetric[3+2]cycloaddition reaction of intermediate olefin II-2 and azomethine ylide II-3,giving fully substituted pyrrolidine derivatives with high yield（up to 97%）and high enantioselectivity（up to 97%）.Then,the[3+2]cycloaddition reaction of terminal electron deficient olefin II-5 and azomethine ylide II-3 catalyzed by（1R,1R）-1,2-cyclohexanediamine-derived phosphinamide ligand II-1e/Ag₂O was investigated,affording2,4,5-trisubstituted pyrrolidine derivatives with high enantioselectivity（up to 95%）and yield（up to 92%）.2.Study on asymmetric[3+2]cycloaddition reactions catalyzed by cinchona alkaloid-derived Amidphos/Ag（I）:First,some bulky sterically hindered arylphosphonobenzoic acids were synthesized.Amidphos/Ag（I）derived from cinchona alkaloids and arylphosphonobenzoic acids catalyzed asymmetric[3+2]cycloaddition of azomethine ylides withα-substituted acrylates.The optimal reaction conditions were III-8e/Ag₂O/toluene at-5 ^oC.Different azomethine ylides andα-substituted acrylate substrates were screened separately,and a series of4,4-disubstituted pyrrolidine derivatives were synthesized with excellent yield（up to 98%）and enantioselectivity（up to 99%）.3.Construction of the core structure of deethylibophyllidine alkaloids:First,the asymmetric[3+2]cycloaddition involving 1,3butadienoate was studied.The optimal reaction conditions were determined:Ag₂O/III-8n/toluene at room temperatures.The substrate suitability of this reaction was explored,affording 19 pyrrolidine derivatives with excellent enantioselectivity（up to 99%ee）and good yield（up to 83%）.Starting from pyrrolidine compound IV-3t,the five membered fused ring core skeleton of deethylibophyllidine alkaloids was successfully constructed via seven steps,including[1+2]cycloaddition,aza MBH reaction,Barton decarboxylation reaction and so on.