Cinchona Alkaloids Organocatalyzed Asymmetric Henry、Michael Reactions Of Isatin Or Isatin Derivatives

The dissertation consists of three parts:(1) Enantioselective Henry reaction of isatin and nitromethene; (2) Enantioselective Michael addition of nitromethane to indolylidene-cyanoacetic acetate; (3) Enantioselective Michael addition of ketones to alkylidenemalononitriles.Since 1910, the first organocatalytic cyanohydrin reaction in the presence of quinine/quinidine was proceeded by Bredig’s method with low enantioselectivity (<10%ee). However, this kind of catalysts has arisen chemists’strong interests, and they broadened the application areas of different organocatalysts. Until 2000, the passion of organocatalytic research was pushed to the climax contributing to the excellent work of List, Barbas III, MacMillan et. al. Considering the advantages of organocatalysis, especially without metal contained, chemists would like to apply it on medicine and natural products’synthesis. And a mount of good results have been achieved.Cinchona Alkaloids are very useful in asymmetric catalysis. In this dissertation, we used three of them, cuprine, quinine thiourea, and amino quinine, to catalyze Henry reaction and Michael addition with high enantioselectivity. Enantioselective Henry reaction of isatin and nitromethene was performed at-15℃in DMA, catalyzed by cuprine (10mol%) with 10mol% PhCOOH as additive. The chiral product could be obtained with 99% yield and 92%ee, and after the further treatment by CH2Cl2, enantioselectivity was raised up to 99%ee. The addition product could be transformed into (+)-Dioxibrassinin with two steps or (-)-S-Spirobrassinin with an additional step, the later is natural cruciferous phytoalexins.The enantioselective Michael reaction of nitromethane to indolylidene-cyanoacetic acetate 3-8, catalyzed by quinine thiourea without solvent at -10℃, was the second topic research. The product could be obtained with high yield (99%) and high enantioselectivity (88%ee). After the reduction of -NO2 into -NH2, the addition product 3-10b could be transformed into spiro[oxindole] amide compound 3-11 whose crystal structure helped us determine the stereo-configuration of product 3-10.The third topic was about enantioselective Michael addition of ketones to alkylidenemalononitriles 4-6 which was catalyzed by amino quinine with high yield (92-95%) and high ee value (92%ee). The enantioselectivity would become better (95%ee) if the three-component "one pot" addition of isatin, malononitrile, and acetone was reacted under the same condition. As we found that the addition of (R)-BNPH as additive could increase the ee value greatly from 75% to 92%. Then cycloaddition of chiral product 4-7a with NaBH4 occurred to give the corresponding spiro dihydropyran compounds 4-8a.Additionally, The stero-structures of new compounds were determined by X-ray tests, followed by nuclear magnetic resonance spectroscopy (1H and 13C), high performance mass spectrometry, optical rotation, and melting point.