Application Of Chiral Ligand Bearing Ferrocene Skeleton In Asymmetric Hydrogenation Of Trifluoromethyl Ketones

The chiral secondary alcohol structural unit containing trifluoromethyl groups is a building block for many biologically active compounds and an important intermediate for the synthesis of complex molecules.The efficient preparation of such compounds is a hot topic in modern organic chemistry.Transition metals-catalyzed hydrogenation can reduce prochiral trifluoromethyl ketones to corresponding alcohol which is one of the most efficient methods to construct trifluoromethyl substituted secondary alcohol chiral structures.Recently the complex Ir/f-amphox,Ir/f-amphol,Ir/f-ampha,Ir/f-amphamide developed by zhangxumu group achieved extremely excellent enantioselectivities and high TON in asymmetric hydrogenation of ketone.These ferrocene-based tridentate ligands are featured by good stability,easy synthesis,wide applicability,rich electroni cs,large steric hindrance.The asymmetric catalytic hydrogenation of trifluoromethyl substituted ketones is a challenging task.Although some research have been made,overall,there are still challenges such as inefficient catalytic systems and limite d substrate range.The chiral iridium complex,generated in situ from iridium and f-amphol and f-ampha catalyzes the asymmetric hydrogenation of trifluoromethyl substituted ketones in the presence of sodium hydroxide as base in toluene to give trifluoromethyl chiral secondary alcohol under mild conditions(25 oC and 40 atm H2).This method has the very good substrate universality,and has excellent stereo control and chemical selectivity.The enantioselectivity is up to 98% and the S /C is up to 1 000.At the same time,we have studied the application of the methodology by means of late stage functionalization,in order to obtain drug molecules containing trifluoromethyl substituted chiral secondary alochol structure.In addition,due to the similar structure of trifluoroacetophenone and acetophenone,but there is a huge difference in electrical properties,we used on-line fourier transform infrared detection to study the kinetic process of these two compounds in the same reaction system.Under the conditions of the catalytic system developed in this project,it was found that the reaction rate of trifluoroacetophenone is much greater than that of acetophenone.