The Research Of Asymmetric Oxidative Aza-diels-alder Reactions And Oxa-michael Addition Reactions By Organocatalysis

Jacobsen described the highly enantio- and diastereoselective synthesis of optically active benzo[a]quinolizine-2-ones catalyzed by a primary aminothiourea catalyst through the formal aza-Diels-Alder Reactions in 2013, which are the key intermediates often in the synthesis of bioactive compounds attracting the interest of organic chemists to develop new synthetic methods. Inspired by the results obtained by Jacobsen and in view of the aspects of step economy and sustainable chemistry, herein we report the first example of oxidative aza-Diel-Alder reaction for the enantio- and diastereoselective synthesis of benzo[a]quinolizine-2-ones by organocatalysis. This article first researched the asymmetric oxidative aza-Diel-Alder reaction of 1,2,3,4-tetrahydroisoquinolines (THIQ) and enones. Through explored the oxidative system?amine catalyst?acid?solvent?temperature, Finally, We acquired excellent yield(62%)?high enantioselective(87% ee) and diastereoselective(>10:1 dr). In the aspect of adaptive of substrate. This reactions has well scope of substrate adaption,Which can obtain highest enantioselective (97% ee) by meta-nitro phenyl enone.The indole derivatives are important compound, the pharmaceutical compounds that containing indole group is quantity, like vinblastine?indometacin?melatonin and so on. These pharmaceutical compounds have significant effect in pharmacology for resistance cancer and treating infectious disease. Therefore it is necessary to research about indole derivatives, which contain the synthesis methodology of indole derivatives.This article use the indolone derivatives and cinnamyl aldehyde as reactant to expect occur asymmetric oxa-Michsel addition reaction. Through screened the amine catalyst?acid?temperature, We finded that catalysis by diphenyl pyrrolidine methanol,and exists in acetic acid can Successfully obtain the chirality indole groups ether compounds by asymmetric oxy-Michael addition reaction. This reaction have excellent yield and medium level of enantioselective(50% ee). This methods of synthesis provide a new approach for synthesis indole groups pharmaceutical molecules that can resistance to cancer.