The Catalytic Asymmetric Reaction Of3-cyanoacetyl Indoles

3-substituted indole unit commonly found in many natural products, there is anextremely important position in pharmaceutical chemistry. Many biologically activecompounds containing3-substituted indole framework, which have broad spectrum ofbiological properties, such as anti-cancer, anti-tumor, hypoglycemic, anti-bacterial, andantipyretic. Therefore,3-substituted indoles have a very important practicability, causedwidespread concern in scientific research. Over the past few years, more and more attentionwas paid to the synthetic methods and structural decoration of indole derivatives and manyreports referred to synthesis of3-substituted indole derivatives, while very few asymmetricmethods have been reported.The asymmetric catalytic reactions of3-cyanoacetyl indoles were investigatedthrough two different methods. On the one hand,3-cyanoacetyl indole as an electron donorof Michael addition reaction reacted with different electron acceptors by the catalysis ofchiral organocatalysts. On the other hand,3-cyanoacetyl indoles reacted with aromaticaldehydes, and then the corresponding products serving as Michael acceptors reacted withdifferent electron donors under the catalysis of chiral organocatalysts.A series of (E)-3-aryl-2-(indole-3-ylcarbonyl)acrylonitriles was synthesized. Theorganocatalyzed enantioselective cascade sulfa-Michael/Michael addition reaction of (E)-3-aryl-2-(indol-3-ylcarbonyl)acrylonitriles and (E)-4-mercapto-2-butenoic acid ethyl esterwas investigated. The reaction condition was optimized as using10mol%catalyst, tolueneas solvent and at room temperature. Then the substrate scope was investigated. This processwas promoted by chiral squaramide catalyst to afford chiral3-substituted indole derivativescontaining tetrahydrothiophene with three contiguous stereocenters in excellentdiastereoselectivities (up to>20:1dr) with moderate to good yields and enantioselectivities(up to93%,89%ee).In addition,3-cyanoacetyl indole as the electron donor reacted with electron acceptors(such as nitro olefins,2-benzylidene-malononitrile, etc.), and the reactions were catalyzedby chiral organocatalysts. Moreover,(E)-3-aryl-2-(indol-3-yl-carbonyl)acrylonitrilesreacted with other electron donors (such as nitromethane, malononitrile, etc.) catalyzed bychiral organocatalysts. But the catalytic results of the reactions were poor.