Organocatalytic Synthesis Of Structurally Diverse Chiral Spirooxindoles Derivatives

The chiral spirooxindoles have the unique biological activity and important medicinal value. In recent years, much attention is focused on the asymmetric organocatalytic synthesis of spirooxindoles in high stereoselectivity by chemists and medical scientists. In this context, the efficient catalytic system and reaction system were designed and constructed to highly stereoselective synthesis of structurally diverse chiral spirooxindoles via organocascade and 1,3-dipolar cycloaddition strategies.The first part in this context, under the catalysis of the cupreine, the organocatalytic three-component reactions via a one-pot, cascade Knoevenagel /Michael / cyclization of isatins, malononitrile and 4-hydroxyquinolin-2-ones delivered a series of chiral spiro[4H-pyranoquinolines-3,3′-oxindoles] which have a spiro quaternary carbon chiral center in moderate to high chemical yields with excellent enantioselectivities. Moreover, the products comprised of indole and pyranoquinolines moieties have the potential bioactivities and important research value.The second part in this context, we have studied the Et3N-catalyzed [3+2]cycloaddition of 3-isothiocyanato oxindoles with barbiturate-based olefins systematically. A wide range of chiral dispirooxindoles containing spiro barbiturate structure were obtained in high chemical yields and excellent diastereoselectivities.The relative configuration of the dispirooxindoles was unambiguously determined by X-ray single crystal structure analysis. The reaction mechanism was proposed to shed light on the diastereoselective formation of the products. Furthermore, with a purpose of gaining potentially biologically active homodimers, we chose one of the dispirooxindoles to design and synthesize disulfide-linked homodimer in 60%chemical yield.The third part in this context, on the basis of the second part work, catalyzed by cinchona-based thiourea, the [3+2] cycloaddition of barbiturate-based olefins with3-isothiocyanato oxindoles furnished the chiral dispirobarbiturates oxindoles containing two spiro and pyrrolidine structure were synthesized in up to > 99%chemical yields with > 99% ee and up to >20:1 dr. The absolute configuration of the products was unambiguously determined by X-ray single crystal structure analysis.The reaction mechanism was proposed to shed light on the enantioselective formation of dispirobarbiturates oxindoles. In addition, we also carried out several chemical transformations by choosing one of the chiral dispirobarbiturates oxindoles as starting material and the obtained products gained high chemical yields with excellent enantioselectivities and diastereoselectivities as before.