Asymmetric Henry Reaction Of 2,2,2-trifluoromethylacetophenone Catalyzed By Chiral Thiourea

Trifluoromethyl-substituted compounds,especially chiral trifluoromethyl compounds,are widely applicated in pharmaceutical,agrochemical and materials science.In recent years,a variety of ways to build a stereogenic center bearing trifluoromethyl group have been explored.Among them,the asymmetric trifluoromethylation reaction using trifluoromethyl building blocks is particularly noticeable.At the same time,chiral thiourea is widely studied as an efficient small organic catalyst.Therefore,this paper focuses on the asymmetric Henry reaction of2,2,2-trifluoromethylacetophenone with nitromethane catalyzed by simple difunctional thiourea.Secondly,this thesis also explored the difluoroalkylation of8-aminoquinolinamides and ethyl 2-bromo-2,2-difluoroacetate catalyzed by Cu?II?.This paper is divided into three parts.Chapter one:Study on Asymmetric Trifluoromethylation Based on Trifluoromethyl building BlocksThis chapter begins with a brief overview of the asymmetric trifluoromethylation of trifluoromethyl buliding blocks from two aspects.On the one hand,the reaction of asymmetric trifluoromethylation catalyzed by organometallic is described.The organic metal catalysts are mainly composed of titanium,nickel,zinc,copper,silver,zirconium,rhodium,palladium and lanthanum.On the other hand,the asymmetric trifluoromethylation catalyzed by organic small molecules is discussed.Including chiral proline,chiral diamines,chiral thiourea,cinchona alkaloids and chiral phosphoric acid catalyzed asymmetric trifluoromethylation.Chapter two:Asymmetric Henry reaction of 2,2,2-trifluoromethylacetophenone as a trifluoromethyl building block with chiral thiourea catalysisIn this chapter,we used simple bifunctional thiourea as an organic small moleculecatalysttoexploretheasymmetricHenryreactionof2,2,2-trifluoromethylacetophenone as a trifluoromethyl building block.The trifluoromethyl-substituted chiral products was obtained with in excellent yields with good enantioselectivities?up to 84%?.Chapter three:Difluoroalkylation of 8-aminoquinolinamides with ethyl bromo difluoroacetate catalyzed by Copper?II?In this chapter,we investigated the difluoroalkylation of 8-aminoquinolinamides and ethyl bromo difluoroacetate catalyzed by cheap CuCl₂.After a preliminary optimization,the fluoridewas obtained in 40%yield.