Study On The In Intramolecular Asymmetric Friedel-Crafts Reaction And Ene Reaction Of Benzyl Malonic Esters

1,2,3,4-tetrahydroquinoline and 1,2,3,4-tetrahydroisoquinoline represent important building blocks,which are widely found in natural products and pharmacological active molecules.In this dissertation,1,2,3,4-tetrahydroquinoline and 1,2,3,4-tetrahydroisoquinoline derivatives were successfully synthesized via intramolecular indole-derived C2-asymmetric Friedel-Crafts reactions and Ene reactions of benzyl malonic esters.1.Using indole-derived benzyl malonic esters as substrates,the nickel-catalyzed intramolecular asymmetric Friedel-Crafts reactions was realized to construct1,2,3,4-tetrahydroisoquinoline derivatives.After the systematic optimization of reaction conditions by screenning transition metals,solvents,temperature,chrial ligands and substrates,the optimal conditions was selected as:using Ni（Cl ₄）₂·6H₂ as catalyst,3,5-dimethyl BIPHEP as chiral ligands,chloroform as solvent at 40 ^oC for 4 hours,the intramolecular asymmetric Friedel-Crafts reactions occurred smoothly,giving 9examples of 1,2,3,4-tetrahydroquinolines in good yields（88%-97%）and enantioselectivity（74%-82%）.2.Using isopentene benzalhydantoin ethyl malonic acid as substrates,the nickel-catalyzed intramolecular asymmetric Ene reaction was developed to build1,2,3,4-tetrahydroquinoline derivatives.By carefully screening the transition metals,temperature,solvents,chiral ligands,and substrate-tuning（ester groups,e.g.）the conditions of at,Ni（Cl ₄）₂·6H₂ as catalyst,3,5-dimethyl BIPHEP as chiral ligands,toluene as solvent at 60 ^oC for 12 hours.the intramolecular asymmetric Ene reactions can be realized to afford 11 examples of 1,2,3,4-tetrahydroisoquinolines with good yields（75%-96%）,enantioselectivity（10%-86%）and diastereoselectivity（1:3-1:18）.