Azacyclocarbene Catalyzed The Asymmetric Cycloaddition Reaction Of ?-position Of Carbonyl Compounds

As the basic synthetic blocks in the organic synthesis,nitriles compounds are widely found in natural products,pharmaceuticals and pesticide molecules.How to synthesize chiral nitriles compounds in a green,simpe and efficient way has always been a problem,especially cyano group-containing on a chiral all-carbon quaternary stereocenters.Organocatalysis has been widely studied by researchers since it has been conceptualized and has been extensively studied.Owing to its simple operation,non-toxic,mild reaction conditions and facile post-processing advantages,organocatalysis has been widely used in the field of organic synthesis.N-Heterocyclic carbine(NHC)is a rising star in organocatalysis.Because of its unique catalytic activation mode,NHC can not only control the existing reaction with high yield and high enatioselectivity,but also can synthesize the novel compounds that traditional method can not synthesize.After nearly two decades of research and development,the N-Heterocyclic carbene has been widely used in the efficient construction of C-C bond and C-X(X = O,N,S)bond and achieved remarkable results.In this paper,we studied the synthesis of cyano group-containing chiral quaternary carbon compounds by using N-Heterocyclic carbene and the preliminary discussion on the bioactivity of these compounds.1.Catalyzed by chiral N-Heterocyclic carbene and oxidized by 3,3?,5,5?-tetra-tertbutyldiphenoquinone,the a(11)?-unsaturated acylazolium intermediate was formed,and reacted with ethyl acetoacetate.The cyano group-containing chiral quaternary all-carbon molecules were synthesized with high yield and high stereoselectivity at 0 ?.With a range of ?-cyano enal examined,we found these compounds react well with ethyl acetoacetate in this study,in which part of the substrate yield can be up to 90%,ee value up to 98%.This method avoided the use of toxic cyanide sources,such as HCN and KCN,provides a new strategy for the efficient construction of chiral cyano compounds.2.The results showed that the above compounds had some bioactivity against the X.oryzae,and the activity of the compound was not obvious good.The inhibition rate of compound(R)-ethyl-4-(4-chlorophenyl)-4-cyano-6-methyl-2-oxo-3,4-dihydro-2H-pyran-5-carboxylate was 90 ± 7.6 % at a concentration of 200 ?g /mL,X.oryzae,52 ± 6.0% at the concentration of 100 ?g / mL.