Catalytic Asymmetric Friedel-Crafts Reaction Of Novel Aromatic Substrates

Catalytic asymmetric Friedel-Crafts alkylation reaction represents one of the most significant approaches to the synthesis of chiral aromatic compounds bearing benzylic stereogenic centers.It has been a focused topic for organic chemists in past decades.Although a range of aromatic compounds,including phenols,phenol ethers,anilines,and electron-rich heteroaromatic compounds,have been widely used in this reaction;it is indeed very limited.We therefore anticipitate to extend the aromatic substrates in the asymmetric Friedel-Crafts reaction,and in this dissertation highly enantioselective Friedel-Crafts alkylation reaction of 3-substituted indoles and ferrocene have been developed.1.The enantioselective Friedel-Crafts C2-alkylation reaction of 3-substituted indoles with?,?-unsaturated esters was developed with chiral Lewis acid catalyst.After the systematic optimization of reaction conditions through solvent screening,examination of chiral ligands,investigation of Lewis acids and so on,the optimal condition was deifined as:1 mol%of Cu-bisoxazoline complex,the reaction proceeded efficiently in CH₂Cl₂ at room temperature for12 hours,giving the excellent yields(92%-99%)and moderate to excellent enantioselectivities(55%-93%).2.Highly enantioselective Friedel-Crafts alkylation reactions of ferrocene with N-sulfonyl?-ketiminoesters and trifluoroacetyl compounds were developed with chiral Lewis acid catalyst.After the systematic optimization of reaction conditions through solvent screening,examination of chiral ligands,investigation of Lewis acids and so on,the optimal condition was deifined as:10 mol%of Ni-bisoxazoline complex,the reaction proceeded efficiently in CH₂Cl₂ at 100 ^oC or 70 ^oC for 12 hours afforded desired products in good to excellent yields(61%-98%or80%-99%)and enantioselectivities(94%-99%or 60%-92%ee).