Studies On Organic Catalysis For The Construction Of Spirocyclic Oxindoles

Spirooxindoles are widely found in many natural products and drug active molecules.Because of their good biological activity and potential drug value,scientists have paid much attention to them.In recent years,many elegant synthetic methods for the construction of this privileged structural motif have been developed,but the development of new methods for the efficient formation of structurally rich spirooxindoles is still in great demand.First,a one-pot 1,3-dipolar cycloaddition of 3-amimooxindole-based azomethine ylides withα,β-unsaturated acyl phosphonates and subsequent derivatization of the intermediates is described.Employing the Br?nsted base 4-（N,N-dimethylamino）pyridine（DMAP）as a robust catalyst leads to an architecturally diverse set of spiropyrrolidinyl-2,3′-oxindoles bearing four contiguous stereocenters and an ester or an amide at theγ-position of the pyrrolidine motif.The products are obtained in moderate to excellent yields and with good diastereoselectivities under mild conditions.The new compounds were characterized by¹H-NMR,¹³C-NMR and MS,and the mechanism of the reaction was proposed.Then,a novel Michael/alkylation cascade reaction of N-unprotected3-bromooxindoles withα,β-unsaturated acyl phosphonates using DABCO as a robust catalyst followed by the derivatization of the acyl phosphonate intermediates in situ was developed.This scenario enables a rapid access to a diverse set of highly functionalized spirocyclopropyl oxindoles in moderate yields with good to excellent diastereoselectivities.The new compounds were characterized by¹H-NMR,¹³C-NMR and MS.Moreover,the reaction mechanism was tentatively elucidated by control experiments and dynamic high-resolution mass spectrometry studies.