Asymmetric Hydrogenation Of ?-keto-?-enamide And Application Based On Iridium/F-amphox Catalytic System

The asymmetric reduction of ketone is a very important class of reaction in organic chemistry.Chiral alcohols have a wide range of application values in medicine,pesticides,spices,natural products,fine chemical products and functional materials.Asymmetric catalytic hydrogenation of ketone is an important method for obtaining highly optical pure and highly active chiral alcohols.This reaction has many characteristics such as high efficiency,high stereoselectivity,and excellent atomic economy.A large number of bidentate ligands,tridentate ligands and multidentate ligands have been successfully used in the field of asymmetric hydrogenation of ketone catalyzed by iridium.Some excellent catalytic systems have been developed,including the systems of f-amphox,f-amphol,and f-ampha designed by the Zhang group.These three new tridentate ligands are stable,easy to synthesize,and have wide applicability to substrates.Benazepril and ramipril are used to treat high blood pressure,congestive heart and acute myocardial infarction and other major diseases.The intermediate fragments of these drugs all contain the structure of ethyl?S?-2-hydroxy-4-phenylbutyrate.In order to obtain highly chiral alcohols with high activity and optical purity,we intend to gathering the novel catalytic system of iridium and tridentate ligands developed by our group,which would be together applied to the synthesis of important chiral alcohol fragments with excellent yields and high enantioselectivity.These chiral alcohols could be transformed to drug intermediates conveniently.Based on the research results of the group,this paper has further explored the asymmetric hydrogenation system of the novel tridentate ligands f-amphox,f-amphol,f-ampha and transition metal iridium in ketone.Through examining a series of?-keto-?-enamide substrates,the results show that the iridium/f-amphox catalytic system has very good effects on substrates with high efficiency,high yield in mild conditions?25?,20 atm H₂?.The results can be up to 99%yield and 98%enantioselectivity,and the reaction is very good substrate universality,the highest turnover number reached 10000.