Stereoselective Construction Of Five-or Six-membered Heterospirocyclic Oxindoles

Spirooxindoles, which are the core structures of numerous alkaloids and drug molecules, have become important synthetic targets with respect to their significant biological activities and applications for pharmaceutical lead discovery. While the synthesis of spirocyclic oxindoles has continued to gain much attention, the development of highly stereoselective methods to access spirooxindoles remains an ongoing synthetic challenge.In this thesis,1,3-dipolar cycloadditions of isatins, benzylamine and benzylideneacetones were studied to prepare a series of novel spiropyrrolidine oxindoles-4’-acetyl-3’,5’-diarylspiro-[indoline-3,2’-pyrrolidin]-2-ones and3’-acetyl-4’,5’-diarylspiro-[indoline-3,2’-pyr-rolidin]-2-ones in good yields (up to94%) and regioselectivities. The opposite regioselectivities were achieved via the addition of water or4-nitrobenzoic acid respectively. The substituent effects on the regioselectivity were also investigated.On the other hand, organocatalytic hetero-Diels-Alder reactions of aryl enones with isatins, providing highly diastereomerically and functionalized syn-spirooxindole tetrahydropyranones, were also studied. A series of L-proline derivatives as catalysts were screened. The effects of solvent and additives were also investigated.5novel spirooxindole tetrahydropyranones were synthesized in good yields (up to84%) with high diastereoselectivities (>20:1) under the optimized conditions. The enantioselectivity for this reaction was also preliminarily studied.