Liu Zhong, He Jia-Hao, Zhang Ming, Shi Zhu-Jun, Tang Han, Zhou Xin-Yue, Tian Jun-Jie, Wang Xiao-Chen
State Key Laboratory and Institute of Elemento-Organic Chemistry, Haihe Laboratory of Sustainable Chemical Transformations, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin 300071, China.
J Am Chem Soc. 2022 Mar 23;144(11):4810-4818. doi: 10.1021/jacs.2c00962. Epub 2022 Mar 8.
Achieving C3-selective pyridine functionalization is a longstanding challenge in organic chemistry. The existing methods, including electrophilic aromatic substitution and C-H activation, often require harsh reaction conditions and excess pyridine and generate multiple regioisomers. Herein, we report a method for borane-catalyzed tandem reactions that result in exclusively C3-selective alkylation of pyridines. These tandem reactions consist of pyridine hydroboration, nucleophilic addition of the resulting dihydropyridine to an imine, an aldehyde, or a ketone, and subsequent oxidative aromatization. Because the pyridine is the limiting reactant and the reaction conditions are mild, this method constitutes a practical tool for late-stage functionalization of structurally complex pharmaceuticals bearing a pyridine moiety.
实现吡啶的C3选择性官能化是有机化学中一个长期存在的挑战。现有的方法，包括亲电芳香取代反应和C-H活化反应，通常需要苛刻的反应条件和过量的吡啶，并且会生成多种区域异构体。在此，我们报道了一种硼烷催化的串联反应方法，该方法能够实现吡啶的专一性C3选择性烷基化。这些串联反应包括吡啶硼氢化、所得二氢吡啶对亚胺、醛或酮的亲核加成，以及随后的氧化芳构化。由于吡啶是限量反应物且反应条件温和，该方法构成了一种用于对含有吡啶部分的结构复杂药物进行后期官能化的实用工具。
