Chiral Nickel-Bisoxazoline Complexes Catalyzed Asymmetric Friedel-Crafts Reaction

Nickel-Lewis acid is an efficient catalyst widely used in organic synthesis. A series of important reactions, such as Michael addition, Aldol reaction, Mannich reaction, and cycloaddtion reaction, could be smoothly performed using Nickel Lewis acid as catalysts. Friedel-Crafts reaction is an important carbon-carbon forming reaction leading to aromatic derivatives. Since1990, the asymmetric Friedel-Crafts reaction for the direct construction of chiral benzylic stereocenters has been extensively studied. The asymmetric Friedel-Crafts reaction of electron-rich aromatic compounds with aldehydes, ketones, imines, and electron-deficient olefins as alkylating agents was investigated systematically and intensively. Various of chiral Lewis acid, Bronsted acid, and hydrogen bond donor organocatalysts have been used in the field. However, the asymmetric Friedel-Crafts reaction based on Nickel-Lewis acid have been rarely reported, and the study on the construction of all-carbon quaternary stereocenters via asymmetric Friedel-Crafts reaction was much less exploited.Asymmetric Friedel-Crafts reaction of electron-rich aromatic compound and nitroalkene was achieved using chiral complex of nickel and bisoxazoline as the catalysts for the enantioselective construction of all-carbon quaternary stereocenters in the Dissertation. A series of92novel compounds were synthesized, inculding23new substrates of β,β-disubstituted nitroalkenes and69new products of substituted indoles and pyrroles. The mecanism of the Asymmetric Friedel-Crafts reaction using chiral complex of nickel and bisoxazoline as the catalysts was analysized.The chiral nickel Lewis acid catalyzed asymmetric Friedel-Crafts reaction of indoles with nitrostyrenes was first studied, affording the adducts in76-90%yields and72-94%enantioselectivities respectivlly. The optimal reaction conditions were determined to be:10mol%Ni(OTf)2as catalyst,12mol%of chiral bisoxazoline ligand L2-14at25℃in toluene. The absolute configuration of the products was determined to be S by the comparision of optical rotation value compared to the value reported in the literature.Enantioselective construction of all-carbon quaternary stereocenter through Friedel-Crafts reaction was studied by using β,β-disubstituted nitroalkenes as substrates, which gave67-86%yields and up to79%enantioselectivity.27novel compounds were synthesized, including5 new substrates of β,β-disubstituted nitroalkenes substrate and22new Friedel-Crafts products bearing all-carbon quaternary stereocenters.The optimal reaction conditions were selected experimentally as follows10mol%Ni(ClO4)26H2O as catalyst,12mol%of chiral bisoxazoline ligand L3-12at50℃in toluene. Substrate examination showed broad scope for nitroalkenes and indoles.Asymmetric Friedel-Crafts reaction of indoles with β-CF3-β-disubstituted nitroalkenes was then studied. Trifluoromethylated all-carbon quaternary stereoceters were highly enantioselectively constructed (up to97%enantioselectivity) under the optimal reaction conditions:10mol%Ni(ClO4)26H2O as catalyst,12mol%of chiral bisoxazoline ligand L4-15at60℃in toluene.43novel compounds were synthesized, including18new β-CF3-β-disubstituted nitroalkene substrates and25new products bearing trifluoromethylated all-carbon quaternary stereoceters. The absolute configuration of the products was determined to be R through single crystal X-ray analysis.Asymmetric Friedel-Crafts reaction of pyrroles with β-CF3-β-disubstituted nitroalkenes was subsequently studied. The reactions occurred efficiently under the conditions of10mol%Ni(ClO4)26H2O as catalyst,12mol%of chiral bisoxazoline ligand L5-11at60℃in toluene, to give84-95%yields and62-91%enantioselectivities respectivlly.22new Friedel-Crafts products were obtained. The transformation of the Friedel-Crafts products to2-substituted indole compounds were realized with complete preservation of enantiopurity.