Asymmetric Friedel-Crafts Alkylation And Relative Tandem Process For Construction Of Chiral Polycyclic Indole Derivatives

Series of enantiomerically enriched oxindoles bearing a quaternary stereocenter,bis-spiro-oxindoles as well as polycyclic indole derivatives were synthesized via asymmetric Friedel-Crafts alkylation and relative tandem and co-catalysis processes.The activity of Friedel-Crafts alkylation of various aromatic compounds to oxindolyl?,?-unsaturated a-ketoesters in different catalystic systems was systematacially investigated.The synthetic strategy in this dissertation provides a new approach to optically active complex indole and oxindole products.In the first part,a newly designed bisoxazoline derived from(R)-BINOL was successfully used in the catalytic asymmestric Friedel-Crafts alkylation reaction between indoles and ?,?-unsaturated a-ketoesters.A series of 3-indolyl substituted oxindole derivatives were obtained in high yields with excellent enantioselectivities with low catalyst loading under mild reaction conditions.The products of this reaction were readily converted to a few significant compounds,such as a-hydroxy esters,a-amino esters and?-keto amides.In the second part,a consecutive(Box)/Cu(?)catalyzed Friedel-Crafts alkylation reaction and sequential co-catalyst mediated intramolecular aldol reaction provided an efficient process for the construction of bispirooxindoles.The key intermediate shaped in the Friedel-Crafts alkylation reaction was readily converted to three different diastereoisomers with high enantio-and diastereo-purity.The transformations between those diastereoisomers were also investigated.In the third part,an efficient cascade asymmetric Friedel-Crafts alkylation/N-hemiketalization/Friedel-Crafts alkylation reaction of 3-alkylindoles with oxindolyl ?,?-unsaturated ?-ketoesters has been developed in the presence of a chiral diphosphine-palladium(?)catalyst.A series of enantiomerically enriched spiro-polycyclic indole derivatives have been constructed in high yields with excellent enantioselectivities and diastereoselectivities.In the forth part,a series of spiro-3,4-dihydropyrans derivatives were obtained with excellect enantioselectivities and diastereoselectivities through[4+2]cycloaddition reaction of 2-vinylphenols and oxindolyl ?,?-unsaturated a-ketoesters.Several transformations of the specially functionalized products were also realized.In the fifth part,asymmetryic[4+2]cycloaddition reaction of electron-rich olefins such as dihydrofuran and dihydropyran was developed depend on the forth part work.Two series of spiro-3,4-dihydropyrans derivatives were obtained with good to excellect enantioselectivities and diastereoselectivities and the mechanism for the reversion of the diastereoisomers was also worded up.