Construction Of Heteroatom-containing Quaternary Stereocenters Via Asymmetric Friedel-Crafts Alkylation Reaction And The Synthesis Of A-DDT

Heteroatom(O,N)-containing quaternary stereocenter is widely existed in natural products.Therefore,the construction of heteroatom-substituted quaternary stereocenters attracts much attention for organic chemists.The asymmetric nucleophilic additions to C=O or C=N double bonds(Strecker reaction,Aldol reaction,Mannich reaction and Henry reaction)has been an effective approach to heteroatom-substituted quaternary stereocenter and has been intensely studied.Friedel-Crafts reaction is one of the important carbon-carbon forming reactions leading to aromatic derivatives.In recent years,the catalytic asymmetric Friedel-Crafts reaction of electron-rich aromatic compound to ketone or imine has been an effective access to construct heteroatom-substituted benzylic quaternary stereocenter.In Chapter 2,asymmetric Friedel-Crafts reaction of indoles with cyclic ketiminoesters was studied.The optimal reaction conditions were founded after the scanning of bisoxazoline ligand,Lewis acid,and solvent as the following:10 mol%of Cu(OTf)2 as catalyst,12 mol%chiral bisoxazoline L2-6 in dichloromethane at room temperature.Reactions proceeds efficiently under the optimized conditions,leading to the desired product in up to 98%yield and up to 99%ee.The synthetic transformations of converting an ester product to the corresponding cyclic chiral N-sulfonyl amido alcohol and the ring-opening reaction of the Friedel-Crafts alkylation product were also carried out.In Chapter 3,the asymmetric Friedel-Crafts reaction of 3-substituted indoles with trifluoropyruvate was studied.The optimal reaction conditions were founded after the examination of ligand,Lewis acid,solvent and others.With 10 mol%of Cu(OTf)2 as catalyst and 12 mol%chiral bisoxazoline L3-14,the reaction proceeds efficiently in the mixed solvent of Toluene/THF(1/1)at 0? or room temperature,affording the corresponding products in excellent yields(up to 98%)and enantioselective(up to 97%).While,the reaction of 3-isopropyl-1H-indole with trifluoropyruvate offered the indolic N1 adduct owing to the steric hinded isopropyl group.In addition,the synthesis of the drug intermediate A-DDT was also studied in this thesis and the author acts a participator in Jiuzhou Pharmaceutical Company.