The Mechanism Research Of 1, 4 Addition Reactions In Asymmetric Drug Synthesis Catalyzed By Rhodium

Since the year of 1992, the US Food and Drug Administration(FDA) began requiring the declaration of chiral drugs, physiological effects of isomers of each drug should be explained very clearly. Because a pair of enantiomers often have different and even opposite physiological activity. High enantioselective synthesis of chiral compounds is of great significance, and is also one of the key scientific problems in the field of drug synthesis. Enantioselective synthesis is one of the most active areas of chemical development, give the strong theoretical foundation and academic basis for the development of chiral drugs, chemicals, materials and spices. Asymmetric 1,4-addition plays an important role and has wide application in the field of chemistry, pharmaceutical industry and material industry, and has been utilized in synthesis of a variety of pharmaceutical products, such as tolterodine, baclofen, paroxetine, platensimycin, MK-O974 and so on. Thus, study of the mechanism of rhodium-catalyzed asymmetric 1,4-addition in the pharmaceutical research is highly desirable.The main work of this paper include Rh catalyzed α,β-unsaturated carbonyl compounds 1,4-addition reaction mechanism with acid reagents, the details are as follows:(1)Using the DFT method, carried out a detailed study of 1,4-addition reaction mechanism of the chiral Rh(I) complex compound catalyzed cyclic α,β-unsaturated carbonyl compounds:2- cyclopentenone, 2-cyclohexenone substrate.(2) Using the DFT method, studied 1,4-addition reaction mechanism of the chiral Rh(I) complex compound catalyzed acyclic α, β- unsaturated carbonyl compounds: an acyclic straight chain(E)α,β-unsaturated enone substrates in detail.