| Pyrrolidine,a five-membered nitrogen-containing heterocyclic ring,is widely found in natural products and pharmaceutical active molecules.Among them,compounds with chiral spiro[benzofuran-pyrrole]scaffolds have received extensive attention because of their special structures and valuable biological activities.For example,Armeniaspiroles with a chiral spiro[benzofuran-pyrrole]scaffold has a significant inhibitory effect on Gram-positive pathogens in vitro;Cephalosporium with this structure displays significant cytotoxicity against P388 cells and HL-60 cells.Therefore,the development of practical methods to realize this structural unit is an attractive subject in organic synthesis.This article mainly studies the highly selective[3+2]cycloaddition reactions of N-2,2,2-trifluoroethylisatin ketimines substituted isatinimine with aurone and its derivatives via the synergistic Br?nsted base and Lewis acid effect with chiral binuclear zinc catalyst to synthesize the spiro compounds with chiral spiro[benzofuran-pyrrole]scaffold.The chiral spiro compounds have three heterocyclic rings and two adjacent spiro quaternary carbon centers.The optimal conditions of the reaction were determined by screening the experimental conditions of the reaction:the catalyst is a complex of 10 mol%L1 and 20 mol%ZnEt2,the substrate-to-material ratio is 1:1,the solvent was toluene,the reaction temperature was room temperature,and the reaction additive was 4A MS.Under these reaction conditions,the applicable scope of the substrate was investigated,and a series of spiro[benzofuran-pyrrole]scaffolds were formed.The yield obtained can up to 95%,the diastereoselectivity can be up to>20:1,and the enantioselectivity can be up to 99%,the absolute configuration of the product was confirmed by the single crystal analyse,and a possible reaction mechanism was proposed based on related literature reports and the binuclear zinc synergistic catalytic mode. |
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