构建三氟甲基取代的全碳型季碳手性中心的催化不对称共轭加成反应研究

Trifluoromethylated organic compounds of pharmaceutical and agrochemical importance have received extensive attention because of the unique impact of the introduced trifluoromethyl group on the enhancement and modification of their original biological activities. The development of reliable synthetic approaches to CF3-bearing organic compounds has been a hot topic in organic chemistry, among which the enantioselective construction of trifluoromethylated all-carbon quaternary stereocenters is much less exploited and remains a very important but extremely challenging task in asymmetric catalysis. The proposed project aims to develop efficient catalytic asymmetric transformations to access chiral compounds bearing trifluoromethylated all-carbon quaternary stereocenters, possessing important scientific significance and great appllied value. Based on the asymmetric conjugate addition reaction, detailed studies include catalytic asymmetric transformations of trifluoromethylated prochiral nucleophiles and electrophiles as well as a domino process of conjugate addition and electrophilic trifluoromethylation reaction, which lead to the construction of trifluoromethyl-bearing all-carbon quaternary chiral compounds in their highly enantioselective fashion. The project focuses on the improvements of the substrate's reactivity, the catalyst's activity, and its asymmetric induction ability, which will be helpful to a more informative understanding of the substituent effect of CF3 group. The success of the project will be a great push to the synthesis of trifluoromethylated chiral compounds and the development of organofluorine chemistry.

三氟甲基类有机化合物由于三氟甲基功能基团的引入，能够有效提高和改善其生物活性，因此在医药农药领域受到广泛关注。三氟甲基类手性化合物的合成则成为有机化学研究的热点，其中不对称催化构建含三氟甲基的全碳型手性季碳结构单元的研究尤为重要但极具挑战性，文献报道非常少，开展相关研究具有重要的科学意义和应用价值。项目拟基于不对称共轭加成反应，研究三氟甲基取代的亲电试剂和亲核试剂的催化不对称转化以及共轭加成与亲电三氟甲基化的串联反应，发展构建三氟甲基取代的全碳型季碳手性中心的高效合成方法。项目围绕提高三氟甲基类底物的反应性和催化剂的催化活性与对映选择性控制性能的核心问题展开研究，实现高对映选择性反应的同时，揭示三氟甲基取代基对反应性及手性控制的影响规律，阐明催化剂的活化机制和手性控制原理，其实施将对三氟甲基类手性化合物的合成以及有机氟化学的研究起到重要的推动作用。