Pd-Catalyzed [3+2] Cycloaddition Reaction Of Vinylethylene Carbonates With Isatins

Spirooxindoles are important frameworks of natural products,drug molecules and selective chemical molecular probes,and its derivatives show unique biological activity and medicinal value.Therefore,the efficient synthesis of such derivatives is an important research topic in organic synthesis.Although a series of synthesis methods have been reported in the literature,the one-pot synthesis of multi-substituted spiroxoindole derivatives with quaternary stereocenters from simple and readily available materials remains a formidable challenge.In this work,we investigated the decarboxylation[3+2]cycloaddition reaction between vinylethylene carbonates(VECs)and isatins catalyzed by palladium,and formed spiroxoindoles bearing two quaternary centers.The details are shown as follows:Using Pd2(dba)3·CHCl3 as catalyst,dppp as ligand,VECs and isatins as substrates,the synthesis of spiraooxindole derivatives were achieved in one step under mild conditions.The method has the advantages of high atomic economy,mild reaction conditions,wide substrate scope,good group tolerance and operational convenience.More importantly,the products could also be synthesized with high yield and good diastereoselectivity,which provides an efficient and simple way for the preparation of complex spirooxindole skeleton.A series of derivatization experiments have proved the application potential of this reaction.In addition,the reaction mechanism was preliminatively explored.And 33 spirooxindole compounds were analyzed by NMR and HRMS,finally,the structures of 4j and 4m were determined by X-ray diffraction.