Synthesis Of Vinyl-arenes Pyrrolidoneferrocenes And Isoquinolinoneferrocenes Respectively Via Palladium-catalyzed Asymmetric Cp-H Alkenylation And Arylation

Recently,palladium-catalyzed ferrocene ortho Cp-H bond activation has developed rapidly,which has attracted extensive attention of researchers.Relatively,its intermolecular reactions are more fully studied,while intramolecular reactions are less reported.Pyrrolidone and isoquinolinone units have important biological and pharmacological activities and are hot spots in drug synthesis.The reports on vinyl-arenes pyrrolidone derivatives are mostly limited to the synthesis of Z/E isomers.However,their studies of chiral control are not sufficient,isoquinolinone derivatives as well.Hence,we hope to synthesize these planar chiral ferrocene derivatives by palladium-catalyzed intramolecular asymmetric C-H bond activation,which is highly significant and challenging.Starting from cheap ferrocene formic acid,ferrocene amine is given by acyl chloride,azide,Curtis rearrangement and Pd/C/H₂.Then ferrocene amine is condensed with arylpropiolic acid or o-bromo arylformyl chloride to obtain N-Ferrocene arylpropiolicamide or N-ferrocene o-bromoarylformamide,which are finally N-protected to obtain substrates for the catalytic reaction.After the template reaction,the effects of ligand,temperature,Pd/L,solvent,and additives on the reaction were investigated,and the optimal reaction conditions were determined.In the study of substrate universality,the compatibility of aromatic rings with electron-withdrawing or electron-donating groups and the effects of steric hindrance and various N-protected groups on the reaction were investigated.Under the optimal reaction conditions,the ferrocene-based pyrrolidone vinyl-arenes were harvested in yields of up to 98%and ee values of 83%.The yield and enantioselectivity of isoquinolinoneferrocenes were as high as 98%and 96%,respectively.