The Asymmetric Catalytic Synthesis Of Chiral Quinolones

The quinoline structural unit is a nitrogen-containing heterocyclic compound widely present in natural products and pharmaceutically active molecules.Its chemical skeleton has numerous biological activities and physiological activities,and has potential pharmacological activity value,and plays an important role in the development of pharmaceutical chemistry.Based on the chiral N-heterocyclic carbene catalyzed synthesis of small chiral drugs,the drug backbone of the chiral polycyclic skeleton system is expected to expand the application of chiral polycyclic skeleton in drug development.For the synthesis of chiral tetrahydroquinoline compounds,the experimental design was carried out by N-heterocyclic carbene(NHC)catalyzed oxidation of ?,?-unsaturated aldehydes to forms unsaturated acyl carbene cation intermediates,followed by N-protected 2-aminochalcone,The reaction produces a multi-stereocentric tetrahydroquinoline compound having a high degree of functionalization.Through the conditional screening,the catalytic system exhibits excellent catalytic efficiency under the promotion of sodium carbonate.The reaction gave the target compound in a yield of up to 98% and an ee value of 99%.On the one hand,the synthesis strategy expands the application of unsaturated aldehydes in N-heterocyclic carbene catalysis,and on the other hand,it is of great significance for the synthesis of quinoline skeleton compounds with pharmacological activity.In addition,based on the synthesis of tetrahydroquinoline compounds,a new synthesis method of chiral dihydroquinolinone was further developed by analyzing its chemical structure.the N-protected 2-aminochalcone and the Cinnamicaldehyde are oxidatively cyclized to form a highly functionalized multi-stereocenter tetrahydrogen by replacing only the base therein with cesium carbonate.Quinoline compounds.The reaction strategy is excellent,and the yield of the target chiral dihydroquinolinone is as high as 83%,and Its enantioselectivity is up to 99%,and the diastereoselectivity is more than 20:1.It is known from the mechanism analysis that the tetrahydroquinoline compound undergoes the C-N bond cleavage and rearrangement to form a chiral dihydroquinolinone compound,which provides a new idea for the asymmetric catalytic synthesis of the dihydroquinolinone skeleton.In summary,this paper developed a new method for the oxidative cyclization of o-aminochalcone with unsaturated aldehydes by chiral carbene catalyzed N protection.By the same system,a functionalized chiral tetrahydroquinoline compound and a chiral dihydroquinolinone compound can be efficiently obtained only by conversion of a base.In particular,the method can construct a novel 3-alkenyl-4-substituted chiral quinolinone skeleton in one step,and the similar method has not been reported,the method is Innovative,simple and convenient,and has excellent stereoselectivity and catalytic efficiency.It is of great significance for the development and expansion of chiral tetrahydroquinoline compounds and chiral dihydroquinolinone compounds.