Catalytic Asymmetric Transformation Of Prochical CF₃ -containing Compounds & Study On Catalytic Multicomponent Reactions

The first part: Chiral -CF3 substituted amine and alcohol are important intermediates of agrochemical and pharmaceutical products. The most efficient and straightforward process towards such molecules would involve the asymmetric transformation of prochical CF3-containing compounds. However, the current methologies mainly rely on using stoichiometric chiral-auxiliary to control facial selectivity. Then, the exploration of more efficient catalytic asymmetric method, which starts with easily handled and commercially available CF3-containing reactant, is of great necessity. In this dissertation, we focus on the chiral phosphoric acid catalyzed three-component Friedel–Crafts-type reaction of trifluoroacetaldehyde hemiacetal, amine with indole, and chiral titanium catalyzed enantioselective alkynylation of trifluoromethyl ketones.Under optimized reaction conditions, a range of novel chiral trifluoro- methyl-containing compounds were obtained with high yields with excellent enantioselectivities by chiral phosphoric acids catalyzed three-component reaction of trifluoroacetaldehyde methyl hemiacetal, aniline and indole. High enantioselectivity was also achieved with difluoroacetaldehyde hemiacetal. Based on the control experiments, a plausible reaction mechanism which involved a multi-hydrogen-bond interaction between the chiral phosphoric acid catalyst and the substrates was proposed.With the pronounced effect of fluoride additive, we initiated an efficient Ti(IV)-catalyzed highly enantioselective alkynylation of trifluoromethyl ketones by utilizing chiral cinchona alkaloid ligands. Commercially available economic catalysts can provide both enantiomers of trifluoromethylated propargylic tertiary alcohols in good to high yields (up to 98%) and enantioselectivities (up to 94% ee). An ESI-MS measurement of the control experiment displayed a base peak at m/z 765.4, pertaining to the existence of the alkynyl transmetallation intermediate. The further preliminary theoretical showed that the zinc-to-titanium transmetallation in a titanium(IV)-catalyzed enantioselective alkynylation reaction was thermodynamically favorable. The combination of experimental and theoretical studies allowed proposal of the mechanistic pathway and chiral induction model. The second part: The catalytic multicomponent reactions have been intensively investigated in recently years. In the presence of Br?sted acid, a three-component Strecker reaction of ketones, amines and trimethylsilyl cyanide smoothly occurred to give the di-substituted -aminonitriles. In the control experiment, the imine intermediate, derived from the ketone and amine, was detected by the 1H NMR and ESI-MS. This protocol has been applied in the catalytic enantioselective three-component condensation process to give preliminary results (20-40% ee).A new method for the synthesis of CF3-substituted furan and pyran derivatives has been accomplished by copper catalyzed three-component coupling reaction of 1,3-dicarbonyl compounds with trifluoroacet-aldehyde hemiacetal and terminal alkynes. The substrate scope and the plausible reaction mechanism were studied.