Cu-prolinol Catalyzed Asymmetric Reactions Of Istain And Its Derivatives

Isatain and its derivatives are the most extensively studied structural moieties of natural compounds.These compounds have broad-spectrum biological and pharmaceutical activities.They can also be used as precursors of photoelectric functional materials with great importance both in scientific research and industrial application.In this dissertation,the stereoselective construction of the oxindole and isoquinoline ring was realized by using chiral copper catalyst,which provided an important synthetic method for the preparation of these compounds.This dissertation includes the following parts:the first part is the diastereo-and enantioselective Mukaiyama aldol reaction of 2,3-indolinedione;in the second part,four carbon centers were constructed by asymmetric Friedel-Crafts reaction of isatain-derivatives;the third part is asymmetric vinylogous aldol reaction of allyl phenyl ketone with oxidized isoquinoline.The following are brief descriptions.In the first part,we realized the Mukaiyama aldol reaction of silyl enol ethers with isatin,constructing the 3-hydroxy-2-oxindole skeleton efficiently under the catalysis of a copper complex,which was prepared by the coordination of copper salt with the chiral tertiary amine ligands.The 3-hydroxy-2-oxindole derivatives can be obtained with high stereoselectivity and the scope of the reaction substrates was extended greatly.In comparison with the previous organocatalysis,we overcome the"fluorine atom effect" of silyl enol ethers,that is,silyl enol ethers without fluorine atom can be also employed as the reaction substrates in the reaction,which extended the scope of the reaction substrates largely.For instance,the glyoxals can be employed as the reaction subtrates.Therefore,the two quaternary carbon centers can be obtained in one step by virtue of this developed method,affording the desired product with both high enantioselectivity and high diastereoselectivity.In addition,we found that the addition of a trace amount of water to the reaction can greatly improve the d.r.value of the target product and significantly enhance the reaction rate.In the second part,we realized the asymmetric alkylation of oxindole derivatives containing unsaturated bonds at the 3-position with electron rich heterocycles catalyzed by the same copper catalyst as that in the first part,constructing the indole ring structure containing chiral all-carbon quaternary stereocenters in one step.In this reaction,we realized the C2,C3 alkylation of pyrrole and C3 alkylation of indole under the same catalyst regardless of the activity and stability of the reactionsubstrates.On the other hand,no obvious electronic effect and steric effect was observed in the extension of the substrate scope.Similarly,the scaling up of the reaction had little influence on the chirality of the product.In addition,the control experiments and DFT calculation supported the coordination between the substrate and the metal,proposing a possible transition state of the reaction.In the third part,we realized the asymmetric vinylogous aldol reaction of allyl phenyl ketone with isoquinoline-1,3,4-trione.By virtue of the addition of the additional base to the reaction mixture,the ketones can be formed conjugated dienols,which was then converted into the isoquinoline-1,3,4-triones.Also,the isatins can be employed as the reaction substrates in this developed reaction.It was found that electronic effect had a great influence on this reaction.Finally,the absolute configuration of the product was determined and the transition state model of the reaction was proposed.In conclusion,we developed a class of efficient methods for the synthesis of chiral nitrogen heterocycles.At the same time,we studied the preparation in detail for oxindole ring and oxidized isoquinoline ring respectively.The chiral heterocycles obtained by this method can be used as important skeletons for the synthesis of drug molecules or natural products,which is of great significance.