The enantioselective synthesis of 3-functionalized oxindole derivatives has experienced an explosive development. This minireview introduces the recent application of rare earth (RE) metal complex catalysts in the synthesis of targeted frameworks. The direct addition reactions of 3-substituted oxindoles or isatins are described, together with a discussion of the catalytic mechanism and related transformations to pharmaceuticals.

Recent progress in enantioselective synthesis of C3-functionalized oxindoles: rare earth metals take action

Conspectus3,3-Disubstituted oxindoles are widely distributed in natural products, drugs, and pharmaceutically active compounds. The absolute configuration and the substituents on the fully substituted C3 stereocenter of the oxindole often significantly influence the biological activity. Therefore, tremendous efforts have made to develop catalytic enantioselective syntheses of this prominent structural motif. Research in this area is further fueled by the ever-increasing demand for modern probe- and drug-discovery programs for synthetic libraries of chiral compounds that are derived from privileged scaffolds with high structural diversity. Notably, the efficient construction of fully substituted C3 stereocenters of oxindole, tetrasubstituted or all-carbon quaternary, spirocyclic or not, also becomes a test ground for new synthetic methodologies.We have been engaged in developing efficient methods for diversity-oriented synthesis of chiral 3,3-disubstituted oxindoles from readily available starting material...

Development of Synthetic Methodologies via Catalytic Enantioselective Synthesis of 3,3-Disubstituted Oxindoles

Transition-Metal-Mediated Routes to 3,3-Disubstituted Oxindoles through Anilide Cyclisation

We report a highly enantioselective Morita-Baylis-Hillman (MBH) reaction of isatins and acrolein to provide enantiomerically enriched 3-substituted 3-hydroxyoxindoles, which could serve as valuable synthetic building blocks. This is also the first time that a ketone has been used as the electrophile and acrolein as the nucleophile in a highly enantioselective catalytic asymmetric MBH reaction. Hatakeyama's catalyst, β-isocupreidine (1), turned out to be a powerful catalyst for this transformation.

Organocatalytic Asymmetric Synthesis of Substituted 3-Hydroxy-2-oxindoles via Morita−Baylis−Hillman Reaction

The organocatalyzed synthesis of a variety of spiro(oxindoles)(γ-butyrolactones) and a benzofuran analogue is based on the high nucleophilicity of the starting indoles and benzofuran (XIX) toward α,β-unsaturated aldehydes.

Satyamaheshwar Peddibhotla

Papers

3-Substituted-3-hydroxy-2-oxindole, an Emerging New Scaffold for Drug Discovery with Potential Anti-Cancer and other Biological Activities