The Application Of Chiral Anion In Asymmetric Bromoaminocyclization And Pd-catalyzed C(sp~3)-H Arylation

Asymmetric counter-anion directed catalysis(ACDC)is a strategy using chiral anion to control the stereoselectivity of asymmetric reactions proceeding via cationic intermediates.In recent years,ACDC has been widely applied in organocatalysis and transition-metal catalysis and become an important strategy to generate chiral compounds.Therefore,the development of novel chiral anions and asymmetric reactions via ACDC strategy will be greatly valuable in organic synthesis.In this thesis,we focus on the development of asymmetric bromoaminocyclaztion of olefins and Pd-catalyzed C(sp3)-H arylation by using chiral anions to control stereochemistry.The novel Br(?)nsted acids of anionic chiral Co? complexes have been revealed as catalysts for a highly enantioselective bromoamioncyclazation of ?-amino-alkenes via chiral anion phase-transfer strategy.The employment of meridional diastereomers of chiral cobalt(?)-templated Br(?)nsted acids,accessed from same chiral source,allows the stereoselective formation of the two enantiomers of 2-substituted pyrrolidines in high optical purity.Hybrid chiral palladium catalysts consisting of a chiral phosphoramidites ligand and an anionic chiral Co? complex have been developed for asymmetric thioamide-directed C(sp3)-H arylation,affording ?-aryl amines in excellent yields and enantioselectivities.Mechanistic investigations reveal the significant synergy between the chiral ligand and the anion in terms of stereochemical control and the matched pair is able to deliver optimal results.A highly efficient and enantioselective ?-C(sp3)-H functionalization of thioamides has been established under the cooperative catalysis of a palladium complex and a chiral phosphoric acid.Using a bulky diisopropylamine auxiliary allows switching the regioselectivity from the carbon adjacent to the nitrogen atom to the acyl side.Mechanistic investigations reveal that two thioamides coordinate to the palladium in the C-H activation step,one undergoing ?-C-H activation and the other acting as a ligand.DFT studies suggest that the stereocontrol is achieved by embedding the substrate in a robust chiral cavity defined by the bulky CPA with a neutral thioamide ligand.