Direct Catalytic Asymmetric Synthesis of Oxindole-Derived δ-Hydroxy-β-ketoesters by Aldol Reactions

Direct asymmetric synthesis of delta-hydroxy-beta-ketoesters was accomplished via regio- and enantioselective aldol reactions of beta-ketoesters with isatins catalyzed by cinchona alkaloid thiourea derivatives. The C-C bond formation of the reactions occurred only at the gamma-position of the beta-ketoesters. Reaction progress monitoring and product stability analyses under the conditions that included the catalyst indicated that the gamma-position reaction products were formed kinetically. Various delta-hydroxy-beta-ketoesters bearing 3-alkyl-3-hydroxyoxindole cores relevant to the development of bioactive molecules were synthesized.