Studies On Asymmetric Mannich And Kabachnik-Fields Reaction Catalyzed By Tartrate-derived Dihydroxy Chiral Phosphoric Acids

Chiral phosphoric acids,which have both Br?nsted acidic and Lewis basic sites,have been developed as a new type of Br?nsted acids.They have been used to catalyze many types of organic reactions,such as asymmetric Friedel-Crafts reaction and Mannich reaction,Michael addition reaction,Biginelli reaction.Though binaphthol-derived chiral phosphoric acids have been widely used in asymmetric catalytic synthesis and been commercialized,their preparation procedures are cumbersome and costly.Both TADDOL and BINOL are widely used chiral diols,while TADDOL-derived chiral phosphoric acids are essential less studied.In this thesis,a series of dihydroxyl chiral phosphoric acids with TADDOL analog framework were designed and synthesized,and their catalytic asymmetric Mannich and Kabachnik-Fields reactions were studied.In chapter 1,recent application of chiral phosphoric acids and ACDC strategy in asymmetric synthesis is reviewed.In chapter 2,a series of tartaric acid-derived dihydroxyl chiral phosphoric acids were designed and synthesized,and their catalytic asymmetric three-component Mannich reaction via chiral counter anions strategy were investigated.Studies have found that dihydroxyl chiral phosphoric acids and silver carbonate can efficiently catalyze the three-component reaction(up to 96% yield,97% ee)of cyclohexanone,aromatic aldehydes and aromatic amines under optimized conditions.Control experiments found that the two hydroxyl groups of the chiral phosphoric acid played a key role in asymmetric catalysis,and the ee value was dramatically decreased after etherification of the two hydroxyl groups.A possible mechanism for chiral counter-anion catalyzed three-component Mannich reaction was proposed.In chapter 3,the asymmetric Kabachnik-Fields reaction catalyzed by the designed and synthesized dihydroxy chiral phosphoric acid was investigated.The influence of catalysts,reaction solvents,temperature,time,and additives on the reaction were preliminarily investigated,and the optimal reaction conditions were determined to be 3,5-bistrifluoromethyldihydroxy chiral phosphoric acid as the catalyst and toluene as the solvent at 40 °C.The 4A molecular sieve is used as an additive,and the yield is up to 94%,ee is up to 79%,which indicates that the dihydroxyl chiral phosphoric acid could effectively catalyze asymmetric Kabachnik-Fields reaction.