Phosphine-Catalyzed[4+1] Cycloadditions Of Allenyl Imides With Ketimines And Enamines

The nucleophilic phosphine-catalyzed cycloaddition reactions show important research value in the synthesis of carbocyclic compounds and heterocyclic compounds.Among them,the cycloadditions of allenes with imines have attracted great attention because of heterocyclic compounds can be constructed through these methods.In this thesis,based on phosphine-catalyzed cycloadditions of allenes with imines involve only research status of zwitterionic intermediates,a novel reaction mode of[4+1]cycloadditions via biselectrophilic intermediate was developed.It mainly includes the following two parts:In the first part,PBu₃-catalyzed[4+1]cycloaddition of allenyl imide with methyl ketimines was presented,which afforded 19 examples of completely substituted cyclopentenonyl enamines with up to 78%yield,using 20 mol%of PBu₃ as catalyst in 1,2-dichloroethane(DCE)at 30°C.Four P-based key intermediates including a1,4-(bis)electrophilic?,?-unsaturated ketenyl phosphonium species have been detected by ³¹P NMR and HRMS analyses,hence,we proposed a plausible reaction mechanism,including:conjugate nucleophilic addition of PBu₃ to allenyl imide would result in the generation of zwitterionic intermediate,which would form?,?-unsaturated ketenyl phosphonium through loss of the 2-oxazolidinyl anion.Then deprotonate methyl ketimines would add preferentially to the electrophilic C(sp)center of?,?-unsaturated ketenyl phosphonium.It undergoes again 1,3-proton transfer,intramolecular Michael addition reaction,1,2-proton transfer and isomerization.The gram-scale experiment of this new chemistry was inspected,which obtained product in 64%yield.At the same time,the synthetic utilities of catalytic product were applied,cyclopentanonyl enamine and cyclopenta[c]pyrazole were respectively obtained through regioselective hydrogenation and annulation with phenyl hydrazine.Finally,based on similar response strategies and Ts NH₂ as a 1N,1N-bisnucleophile.PBu₃-catalyzed or(R)-SITCP[4+1]cycloaddition of allenyl imides with Ts NH₂ was investigated,racemic and chiral?-lactams were gained,respectively(93%yield;42%yield,52%ee).In the second part,In view of similar response strategies and a potential methyl ketimine/enamine tautomerism,PBu₃-catalyzed[4+1]cycloaddition of allenyl imide with phenylacetone-derived enamines was introduced,which confered 11 examples of?-keto ketimines bearing an all-carbon quaternary center in 41–51%yields,using20 mol%of PBu₃ and Cs₂CO₃ as catalysts in 1,2-dichloroethane at 30 or 60°C.