Organocatalytic Enantioselective Mannich-Type Addition Of Isatin-derived Imines

Enantioenriched 3-substituted 3-amino-2-oxindoles is a prevalent core heterocyclic skeleton present in a large number of bioactive natural products and pharmaceutically active compounds.The development of efficient methods for the asymmetric construction of 3-substituted 3-amino-2-oxindoles has been a long pursuing goal in organic synthesis.In particular,the enantioselective nucleophilic addition of isatin-derived ketimines offers an efficient and straightforward access to chiral 3-substituted 3-amino-2-oxindole.So we turned our attention to the nucleophilic such as 5H-thiazol-4-ones,5H-oxazol-4-ones and rhodanines and there are few reports about these three nucleophiles.Besides,we can synthesize 3-substituted 3-amino-2-oxindoles featuring vicinal sulfur or ?-hydroxycarboxylic acid-containing tetrasubstituted stereocenters structural motifs by a simple derivatization reaction.Therefore,This thesis is mainly composed of three parts: Enantioselective organocatalytic Mannich-Type Addition of Isatin-derived Imines to 5H-thiazol-4-ones or 5H-oxazol-4-ones or rhodanines.Part ?: Enantioselective organocatalytic Mannich-Type Addition of 5H-thiazol-4-ones to Isatin-derived IminesThe first chiral phosphoric acid catalyzed enantioselective Mannich-Type addition of 5H-thiazol-4-ones to isatin-derived imines has been established.By using this strategy,the resulting 3-substituted 3-amino-2-oxindoles featuring both 5H-thiazol-4-one and vicinal sulfur-containing tetrasubstituted stereocenters structural motifs were obtained in high yields(81-96%)with excellent enantioselectivities(up to 99% ee)and diastereoselectivities(>20:1 dr).Part ?: Enantioselective organocatalytic Mannich-Type Addition of 5H-oxazol-4-ones to Isatin-derived IminesThe first chiral phosphoric acid catalyzed enantioselective Mannich-Type addition of 5H-oxazol-4-ones to isatin-derived imines has been established.By using this strategy,the resulting 3-substituted 3-amino-2-oxindoles featuring both 5H-oxazol-4-ones and vicinal ?-hydroxycarboxylic acid-containing tetrasubstituted stereocenters structural motifs were obtained in high yields(78-97%)with excellent enantioselectivities(up to 96% ee)and diastereoselectivities(>20:1 dr).Part ?: Enantioselective organocatalytic Mannich-Type Addition of rhodanines to Isatin-derived IminesThe catalyzed enantioselective Mannich-Type addition of rhodanines has been established by employing isatin-derived imines as suitable partners under chiral squaramide catalysis.By using this strategy,the resulting 3-substituted 3-amino-2-oxindoles featuring both rhodanine and vicinal sulfur-containing tetrasubstituted stereocenters structural motifs were obtained in high yields(81-96%)with excellent enantioselectivities(up to 98% ee)and diastereoselectivities(>20:1 dr).