Scholarlink

<p>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<i>π</i>-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 <i>in vivo</i> models confirm the high biosafety and promising antitumor efficacy of these chiral azabicyclic compounds.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 发表日期：

    2026年4月23日

查看全文
  • Jiaxing Guo,
  • Qianyu Chen,
  • Chunyu Han,
  • Xinze Wang,
  • Wenda Xu,
  • Wenli Yan,
  • Huijing Xiang,
  • Xiang Ma,
  • Genping Huang,
  • Xingguang Li

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 4π-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.