Catalytic Stereoselective Synthesis Of Relative Organofluorine Compounds

The application of organofluorine compounds has received extensive attention in the area of pharmaceutical industry, agrochemistry and materials science due to their unique chemical, physical and biological properties. Development of more effective strategies applicable to the synthesis of organofluorine compounds, especially chiral organofluorine compounds, is of considerable important and still in great demand.In general, the synthesis of organofluorine compounds has been focused on a stepwise bond formation process. However, a survey of the literature reveals that catalytic tandem reactions for the construction of organofluorine molecules are rare. In the first part of this dissertation, we have developed a single Lewis acid-catalyzed tandem Nazarov cyclization / electrophilic fluorination transformations of polarized enones into fluorine-containing 1-indanone derivatives. This procedure can create two new stereocenters with excellent diastereoselectivity (trans/cis: 3 / 1― 9 / 1). Furthermore, by emplying the chiral Bis(oxazoline) into our catalytic system, a series of chiral fluorine-containing indanones derivatives have been synthesized with moderate to excellent enantioselectivities. Further extending this protocol to catalytic tandem Nazarov cyclization / chlorination was also proved to be feasible, providing the corresponding chlorinated 1-indanone derivatives with high diastereoselectivity (trans/cis: 6 / 1― 49 / 1).Trifluoromethylated compounds are particularly interesting as the strong electron-withdrawing effect of the CF3 group leads to exceptional properties. One of the applicable strategies for construction of these moleculars is asymmetric transformations of prochiral trifluoromethylated compounds. In the second part of this dissertaition, we have described the first example of chiral Br?nsted acid-catalyzed enantioselective directed arylation of prochiral trifluoromethyl ketones to giveα-trifluoromethyl tertiary alcohols in high yields with excellent enantioselectivities (up to 98% ee). In addition, Our organocatalytic protocol was found to be effective for the enantioselective arylation of ethyl 4,4,4-trifluoroacetoacetate. A series of chiral trifluoromethyl subsitituted tertiary alcohols were obtained in moderate to high yields with up to 78% ee. By a single recrystallization, several adducts could be afforded with excellent optical purities (>99.9% ee). This asymmetric protocol was also extended to the prochiral trifluoropyruvate, while all cases provided quantitative yields with low to moderated ee values (20-62% ee).