Asymmetric Synthesis Of 3,3'-Disubstituted Oxindole Derivatives

The chemistry of oxindoles is very interesting;the oxindole scaffold is present in numerous natural products and has received extensive attention in synthetic organic and medicinal chemistry due to their promising biological activities.Extensive research efforts have been directed toward the development of efficient methods for the asymmetric synthesis of chiral oxindoles.In this thesis,two strategies have been successfully developed for the construction of chiral spirocyclic oxindoles as well as 3,3'-disubstituted oxindoles based on the chiral sulfur ylide and dual palladium/asymmetric organocatalysis,respectively.The first chapter introduces the concept of the chirality and provides a general overview on the representative strategies available for the preparation of chiral molecules in enantiomerically pure forms.Also,this chapter reviews the role of 3,3'-disubstituted oxindole derivatives as interesting target molecules in natural and pharmacological agents of various therapeutic actions,and briefly surveys the synthetic methodologies that are currently available for the asymmetric construction of chiral 3,3'-dialkyled oxindoles as well as spirocyclic oxindoles.The second chapter described the development of an efficient methodology toward synthesis of various enantioenriched spiroepoxyoxindoles from isatins by employing chiral sulfur ylides generated in situ from camphor-derived sulfonium salts under mild reaction conditions,giving high yields and excellent enantio-and diastereoselectivities for a broad range of substrates(up to 99%yield,>95:5 d.r.and 93%ee).Importantly,upon completion of the reaction,the chiral sulfide was recovered in more than 90%yield.Finally,the absolute configuration of the spiroepoxyoxindole was confirmed to be(R,R)by X-ray diffraction analysis,and a possible stereocontrol model for the asymmetric induction was proposed.The third chapter demonstrated the application of the combination catalysis concept in the asymmetric synthesis of the oxindole derivatives.A catalytic asymmetric allylic alkylation reaction of 3-aryl oxindoles has been achieved through a dual catalysis merging palladium catalysis and asymmetric H-bonding catalysis.By doing so,allylated oxindoles with chiral all-carbon quaternary centers were produced in high yields with good enantioselectivities up to 96:4 e.r..Moreover,dual activation is proposed in the transition state based on the absolute configuration of the product,the spectrometric analysis and the previous literature.