Liu Xinyuan's research group of South University of science and technology has made important progress in the field of free radical asymmetric chemistry

Recently, Liu Xinyuan, a professor of Chemistry Department of South University of science and technology, has made important progress in the field of asymmetric carbon carbon bond coupling The research results were recently published in nature Chemistry (DOI: 10.1038 / s41557-019-0346-2) The construction of carbon carbon bond is a very core research field in organic chemistry In many synthesis methods, the coupling reaction of carbon carbon bond has attracted much attention The 2010 Nobel Prize in chemistry was awarded to three organic chemists who have made outstanding contributions in this field Asymmetric carbon carbon bond coupling can be used to construct the carbon skeleton of three-dimensional chiral natural products, drugs, pesticides and materials, and provide an efficient synthesis tool for their modification In the past, the research focus was on the coupling reaction of asymmetric carbon (SP 3) - carbon (SP 3) and carbon (SP 3) - carbon (SP 2), but the coupling reaction of carbon (SP 3) - carbon (SP) was rarely reported However, alkynes are highly reactive and have a variety of conversion methods, which provides the possibility for the rapid construction of chiral carbon (SP 3) - carbon (SP 3) and carbon (SP 3) - carbon (SP 2) bonds through asymmetric carbon (SP 3) - carbon (SP) coupling and corresponding conversion Figure 1 The importance of carbon carbon (SP) coupling reaction in organic synthesis (a); the challenge of oxidative addition of alkyl halogenated hydrocarbons and the side reactions such as B-hydrogen elimination (b); the widespread presence of chiral alkynes in these natural products and drug molecules (c) Sonogashira coupling reaction is the most typical one through carbon carbon (SP ）The method of coupling to construct alkynes This kind of reaction uses simple and easy to get halogenated hydrocarbon and terminal alkyne as raw materials, and does not involve the use of organometallic reagents commonly used in coupling reaction or pre functionalized reagents, so as to avoid possible functional compatibility problems and reaction cost problems Therefore, the successful realization of asymmetric Sonogashira carbon (SP 3) - carbon (SP) coupling will provide an excellent complementary method for the reported asymmetric carbon (SP 3) - carbon (SP 3) and carbon (SP 3) - carbon (SP 2) coupling reactions Based on this, Liu Xinyuan group cleverly designed and developed a catalytic system composed of polydentate anion ligands derived from univalent copper and cinchona alkaloids The polydentate anion ligands not only effectively provide the chiral environment, but also significantly enhance the reduction of copper center Therefore, the group can directly reduce the racemic haloalkanes which are easy to obtain into the intermediate of the chiral alkyl radicals, and further successfully realize the stereoscopic aggregation of Sonogashira carbon (SP 3) - carbon (SP) coupling reaction This reaction substrate has a wide range and excellent enantioselectivity (up to 99% of the excess enantiomers) In particular, both acetylene and propargyne, industrial raw materials, can participate in this transformation efficiently, which provides a solid foundation for the future large-scale industrial application Figure 2 Copper catalyzed three-dimensional convergent carbon bond coupling (I); application of reaction in the conversion of industrial raw material acetylene gas (II); application of reaction in the synthesis of active drug molecules and natural products (II); in addition, the research team also successfully constructed a series of natural products, drugs and carbon in drug lead compounds (SP 3) through this research method - carbon (SP 3) and carbon (SP 3) - carbon (SP 2) bonds This work fully demonstrates the great potential of copper catalyzed free radical reactions in the field of stereoscopic aggregation transformation The first author of this paper is Dong Xiaoyang, a 2017 level doctoral student, Zhang Yufeng, Ma canliang, a postdoctoral fellow of Liu Xinyuan research group, Gu qiangshui, Wang Fuyi, an assistant research professor, and so on Liu Xinyuan is the only communication author, and Nanke university is the only communication unit In addition, Jiang Shengpeng, a postdoctoral student, and Li Zhongliang, an assistant professor of research, also made important contributions to this paper All research projects of the research group of Liu Xinyuan (fourth from the left: Liu Xinyuan, third from the right: Dong Xiaoyang) have been greatly supported by NSFC, special experts of the Ministry of education, Shenzhen Science and technology innovation Commission, Shenzhen Nobel Prize scientists laboratory and other projects.