Organocatalytic Asymmetric Synthesis Of Oxindole Derivatives

In the past few years, extensive research efforts have been directed toward the development of efficient methods for the asymmetric synthesis of chiral oxindoles. In this context, a number of strategies based on organocatalysis have been successfully developed for the construction of3,3’-disubstituted oxindoles as well as spirocyclic oxindoles.Based on the nuclephilicity of the3-substituted oxindole and the great potential in cascade reaction for3-ylideneoxindoles, in the present dissertation, we obtained four kinds of chiral oxindoles with high reaction efficiencies and stereoselectivities. These brief abstracts are listed below:Firstly, an asymmetric Michael addition/diastereoselective protonation cascade reaction of3-substituted oxindoles and ethyl2-phthalimidoacrylate has been uncovered. This strategy can give direct access to Cγ-tetrasubstituted a-amino acid derivatives bearing1,3-nonadjacent stereocenters with up to98%yield,94:6d.r. and>99%ee. Moreover, dual activation is proposed in the transition state based on the absolute configuration of the product. All the protection groups canbe removed easily without loss of enantioselectivity.To furhter demonstrated the utility of the previous strategy, an efficient and practical asymmetric conjugate addition of3-substituted oxindoles to vinylphosphonate catalyzed by easily accessible squaramide catalysts has also been disclosed. This transformation provides a highly efficient method for incorporating the phosphonate unit into oxindole skeletons, affording a new class of oxindole derivatives with up to97%yield,94:6d.r. and>99%ee. Notably, the opposite enantiomers can be obtained simply by changing quinine-derived catalyst to the quinidine analogue.Moreover, we described a Michael/aldol cascade reaction between3-ylideneoxindoles and1,4-dithiane-2,5-diol, which provided an efficient access to a new family of tetrahydrothiophene-fused spirooxindoles bearing three consecutive stereogenic centers with good reaction efficiency and stereoselectivities (74-96%yield,4:1->19:1d.r.,83-91%ee). All the testing starting materials with different substituents and protecting group on the N-atom, including the methyl, allyl and benzyl group canbe well tolerated.At last, we developed an asymmetric Michael addition reaction of3-ylideneoxindoles and acetylacetone by means of readily accessible bifunctional organocatalyst. The reaction exhibit excellent enantioselectivities (more than90%ee basically) and provided an efficient synthesis of enantiomerically enriched polysubstituted oxindoles under benign condition. Importantly,96%ee were observed for both diastereoisomers when nitromethane was employed as the the nuclephile.