C-H Alkenylation of Heteroarenes: Mechanism, Rate, and Selectivity Changes Enabled by Thioether Ligands
C-H Alkenylation of Heteroarenes: Mechanism, Rate, and Selectivity Changes Enabled by Thioether Ligands
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DOI：
10.1021/jacs.7b03887
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发表时间：
2017-07-19
影响因子：
15
通讯作者：
Carrow, Brad P.
中科院分区：
文献类型：
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作者：
Gorsline, Bradley J.;Wang, Long;Carrow, Brad P.
硫醚辅助配体已被发现可以极大地促进O-、S-和N-杂芳烃的C-H烯基化反应。动力学数据表明，硫醚-钯催化的反应速度可以比传统的无配体体系快800倍。此外，机理研究表明C-H键断裂是翻转的限制步骤，硫醚配位的速率加速与这一关键步骤从中性途径到阳离子途径的变化有关。在这些反应中，阳离子、低配位催化中间体的形成也可能解释了不寻常的催化剂控制的位置选择性，其中五原子杂芳烃的C-H烯基化可以在硫醚配体的电子控制下发生，即使这必然涉及到更受阻碍的C-H键的反应。硫醚效应也使得许多O-、S-和N-杂芳烃在温和的条件下反应时间较短(55例)，包括晚期药物衍生化的例子。
Thioether ancillary ligands have been identified that can greatly accelerate the C-H alkenylation of O-, S-, and N-heteroarenes. Kinetic data suggest thioether-Pd-catalyzed reactions can be as much as 800X faster than classic ligandless systems. Furthermore, mechanistic studies revealed C-H bond cleavage as the turnover-limiting step, and that rate acceleration upon thioether coordination is correlated to a change from a neutral to a cationic pathway for this key step. The formation of a cationic, low-coordinate catalytic intermediate in these reactions may also account for unusual catalyst-controlled site selectivity wherein C-H alkenylation of five-atom heteroarenes can occur under electronic control with thioether ligands even when this necessarily involves reaction at a more hindered C-H bond. The thioether effect also enables short reaction times under mild conditions for many O-, S-, and N-heteroarenes (55 examples), including examples of late-stage drug derivatization.