Study On Asymmetric Michael Addition Reaction Promoted By 9-Amino-9-Deoxyepiquinine

The application of 9-amino(9-deoxy)cinchona alkaloids have become more widespread in asymmetric synthesis, they are environmentally friendly and completely recyclable, and the catalysis effect is satisfactory. This dissertation studied their application in asymmetric Michael addition from three parts. The first part was about asymmetric tandem reactions for the synthesis of optically active 2-amino-2-chromene derivatives, the second part was on organocatalytic asymmetric Michael addition and 1,3-dipolar cycloaddition reactions for synthesis of diversely functionalized tricyclic tetrazoles, and the third part was about organocatalytic and direct asymmetric vinylogous Michael addition of 3-cyano-4-methyl-coumarins toα,β-unsaturated ketones.In the current work,9-amino-9-deoxyepiquinine was used in asymmetric tandem reactions between 2-hydroxyaryl-α,β-unsaturated ketones and malononitrile for the first time. The reaction is first to undergo the Michael addition, and then following intramolecular cyclization, namely the nucleophilic addition of the phenolic hydroxyl group on the cyano moiety and proton transfer. Under the optimum reaction conditions, We got the functionalized 2-amino-2-chromene derivatives (up to 84% yield, up to 96% ee), and determined the molecular absolute configuration by X-ray diffraction. Experiments show that the applicable scope of substrates are very extensive.Next, we are interested in the undeveloped asymmetric reactions between 2-azidoarylα,β-unsaturated ketones and malononitrile. We found that 9-amino-9-deoxyepiquinine was efficient organocatalyst for the organocatalytic two-step synthesis of diversely functionalized tricyclic tetrazoles (53:47-63:37 dr, up to 99% ee). Experiments show that the reaction is first to undergo the Michael addition, then following intramolecular 1,3-dipolar cycloaddition. In addition, we also studied one-pot organocatalytic synthesis of diversely functionalized tricyclic tetrazoles, enantioselectivities and diastereoselectivities are slightly reduced.We also found that 9-amino-9-deoxyepiquinine was efficient organocatalyst for the asymmetric vinylogous Michael addition of 3-cyano-4-methylcoumarins toα,β-unsaturated ketones. Under the optimum reaction conditions, functionalized coumarin derivatives were synthesized, Moderate to good yields(51-91%) and highly enantioselectivities(85-95% ee) were obtained.