文献类型：期刊文献

英文题名：Palladium-catalyzed asymmetric [4+3] cycloaddition of cycloamidines with trimethylenemethanes to access chiral bridged [3.2.2] bicycles

作者：Guo, Jiaxing[1];Chen, Qianyu[1];Han, Chunyu[2];Wang, Xinze[1];Xu, Wenda[3];Yan, Wenli[1];Xiang, Huijing[3];Ma, Xiang[1];Huang, Genping[2,4];Li, Xingguang[1]

机构：[1]East China Univ Sci & Technol, Sch Chem & Mol Engn, Shanghai Key Lab Funct Mat Chem, Key Lab Adv Mat, Shanghai 200237, Peoples R China;[2]Tianjin Univ, Int Joint Inst, Sch Sci, Dept Chem, Tianjin 300072, Peoples R China;[3]Shanghai Univ, Sch Life Sci, Shanghai 200444, Peoples R China;[4]Xinjiang Univ, Coll Chem, State Key Lab Chem & Utilizat Carbon Based Energy, Urumqi 830017, Peoples R China

年份：2026

外文期刊名：SCIENCE CHINA-CHEMISTRY

收录：;EI(收录号：20261820637339);WOS:【SCI-EXPANDED(收录号:WOS:001751835700001)】；

基金：This work was supported by the National Natural Science Foundation of China (T2522014, 22571083, 22201073, T2322018, 32171391, 22125803, T2488302, 22471191), the Fundamental and Interdisciplinary Disciplines Breakthrough Plan of the Ministry of Education of China (JYB2025XDXM404), and the Fundamental Research Funds for the Central Universities. We thank the Research Center of Analysis and Test of East China University of Science and Technology for their help in the characterization.

语种：英文

外文关键词：cycloaddition; chiral bridged bicycles; asymmetric catalysis; trimethylenemethane; palladium

摘要：The asymmetric cycloaddition of palladium-trimethylenemethane (Pd-TMM) serves as a powerful method for constructing enantioenriched ring systems. Yet its application to cycloaddends for chiral bridged polycycles remains largely unexplored and challenging, owing to high energy barriers and difficulties in selectivity control. Herein, we report the first asymmetric [4+3] TMM cycloaddition with 4 pi-cycloaddends-cycloamidines, enabling efficient access to diverse chiral bridged azabicyclo[3.2.2]nonanones with multiple stereocenters in excellent enantio- and diastereoselectivity. This transformation is driven by the "push-pull" effect of the amidino moiety and aromatization-assisted C-C bond formation. Computational studies reveal that the initial nucleophilic addition governs both the reaction rate and stereoselectivity. Moreover, evaluations in cellular and in vivo models confirm the high biosafety and promising antitumor efficacy of these chiral azabicyclic compounds.