Enantioselective Formation Of Oxindole Derivatives With Quaternary Stereocenters Catalyzed By Cinchona Alkaloid-derived Chiral Catalysts And C₂-symmetric Bis（Oxazolines）-metal Complexes

1. The introduction of bifunctional thioureas and C2-symmetric bisoxazolinesAsymmetric catalysis has become a powerful tool for the synthesis of chiralcompounds. Herein we introduce some chiral catalysts, such as cinchona alkaloidderived bifunctional thioureas and C2-symmetric bisoxazolines, and their applications inasymmetric catalysis. So far, many reactions have been catalyzed by chiral bifunctionalthiourea catalysts bearing both base moiety and hydrogen-bond donor, the utilization ofwhich has emerged as a viable strategy in the design of efficient organocatalysts forasymmetric organic transformations. C2-symmetric bis(oxazolines)(boxes) are one ofthe most popular classes of chiral ligands applying to lots of reactions and enjoy highprestige and have received a great deal of attention as ligands in asymmetric catalysis.2. The synthesis of bifunctional thioureas and C2-symmetric bisoxazolinesHere, we synthesized some chiral catalysts according to the literatures such asbifunctional thioureas derived from quinine and C2-symmetric bisoxazolines startedfrom (1R,2S)-1-amino-2,3-dihydro-1H-inden-2-ol and malononitrile.3. Efficient Construction of Chiral Spiro Benzo[g]chromene-OxindoleDerivatives via Organocatalytic Asymmetric Cascade Cyclization ReactionThe pyranonaphthoquinone analogus are common in molecular structures withsignificant biological and pharmaceutical activities. Herein, organocatalytic asymmetriccascade Michael cyclization reaction of2-hydroxynaphthalene-1,4-diones toisatylidene malononitriles has been developed using the tertiary amine-thiourea derivedfrom dihydroquinine as a catalyst, which provided the desired spiro4H-benzo[g]chromene-indoline derivatives in up to99%yield with up to99%ee. To illustrate the potential utility of the desired products, further transformation wasconducted to give spiropolyheterocyclic compound in moderate yield without loss ofenantioselectivity (>99%ee). Biological evaluation of thesespirobenzo[g]chromene-indolines and their derivatives have revealed excellentantiproliferative activities against a number of cancer cell lines, with a high inhibitionrate ranging from93%to99%at a concentration of50M.4. Enantioselective synthesis of3-aminooxindole derivatives via an additionreaction catalyzed by C2-symmetric Bis(oxazolines)-metal Complexes3-aminooxindole derivatives were directly synthesized by the addition reaction ofaniline to3-benzyl-3-bromoindolin-2-one in the presence of base. The initialinvestigation showed that the desired compound was obtained smoothly in high yield,but poor enantioselectivity, when using C2-symmetric Bis(oxazolines)-Ni(II) Complexas a chiral catalyst. In order to improve the enantioselectivity, further investigation isnecessary and is ongoing in our lab.