Bifunctional Thiourea Catalyzed Asymmetric Mannich Reaction Using Trifluoromethyl Aldimines As Trifluoromethyl Building Blocks

The organotrifluoromethyl compounds, especially chiral trifluoromethyl compounds have been paid more and more attention in recent years because of their increasingly important role in medicinal chemistry and material science. In recent years, a great number of methods for asymmetric trifluoromethylation of organic molecules have been developed. Of them, enantioselective trifluoromethylation is one of important methods. On the other hand, chiral thioureas used as one of organic small molecule catalysts, have been proved to be efficient in asymmetric catalysis. Therefore, this thesis mainly discussed asymmetric Mannich reaction of trifluoromethyl aldimines and β-ketoesters catalyzed by bifunctional thioureas. Besides, trifluoromethylation of β-ketoesters promted by Ph I(OAc)2 reagent was also explored. The paper consists of three parts: The chapter one: Research Progress in asmmetric trifluoromethylationThis chapter mainly reviewed the study on asymmetric trifluoromethylation from two aspects. the first, four kinds of methods about trifluoromethylation were introduced. The second, all kinds of methods of asymmetric trifluoromethylation were studied, which include trifluoromethylation by using nucleophilic and electrophilic trifluoromethyl reagents and building blocks with fluoromethyl groups. The chapter two: Bifunctional Thiourea Catalyzed Asymmetric Trifluoromethylation via Mannich Reaction Using Trifluoromethyl Aldimine as Trifluoromethyl Building BlocksIn this chapter, we firstly used bifunctional thiourea to catalyze asymmetric trifluoromethylation via Mannich reaction using trifluoromethyl aldimines as trifluoromethyl building blocks and 93% yield and 84% ee value were obtained. Secondly, we also explored the selectivity of some aliphatic β-ketoester’s trifluoromethylation reaction, but it is pity that the results obtained were not satisfactory. The chapter three: Trifluoromethylation reaction of β-ketoesters promoted by PhI(OAc)2 reagentIn this chapter, trifluoromethylation reaction of β-ketoesters promoted by PhI(OAc)2 reagent were explored. We used hypervalent iodine reagent and TMSCF3 instead of Togni reagent to complete trifluoromethylation, and 70% yield was obtained in Trifluoromethylation reaction of β-ketoesters.