Studies On Catalytic Asymmetric Synthesis Of Chiral Oxindole Derivatives

Oxindoles, especially those bearing chiral quaternary carbon center ones arethe basic structural motifs in a large family of natural products and bioactivemolecules which present significant biological and pharmaceutical activities. Thus,the catalytic asymmetric construction of oxindoles bearing a quarternary center isof great importance for organic synthesis as well as drug discovery, and hasattracted much attention in recent years. As the lab’s continuous effort to exploringnew catalytic asymmetric methods, two types of catalytic asymmetric constructionof chiral oxindoles bearing a tetrasubstituted stereocenter have been developed:Based on the enolate mechanism, the chiral tertiary amine thiourea catalyzedenantioselective direct aldol reactions of methyl ynones and isatins under aqueousconditions have been developed, and the desired products3-alkyl-3-hydroxyindol-2-ones were generated in moderate to good yields andenantioselectivies.The asymmetric addition of3-substituted oxindoles to ynones in the promotion of alkaloid derivated urea catalyst afforded the chiral oxindoles bearingelectron-defficient alkenes at the C-3position with high Z/E selectivities andstereoselectivities. The products could be transformed to other optically activecompounds such as chiral amino acids derivatives in conventional conversations,which enhanced the importance of this method.The two strategies developed provided a new access to two types of chiraloxindoles with moderate to excellent stereoselectivities, showing the potential inthe synthesis of natural product derivatives.