Sasmal Sheuli, Prakash Gaurav, Dutta Uttam, Laskar Ranjini, Lahiri Goutam Kumar, Maiti Debabrata
IIT Bombay, Department of Chemistry Powai Mumbai 400076 India
Chem Sci. 2022 Apr 20;13(19):5616-5621. doi: 10.1039/d2sc00982j. eCollection 2022 May 18.
Site-selective C-H alkynylation of arenes to produce aryl alkynes is a highly desirable transformation due to the prevalence of aryl alkynes in various natural products, drug molecules and in materials. To ensure site-selective C-H functionalization, directing group (DG) assisted C-H activation has been evolved as a useful synthetic tool. In contrast to DG-assisted -C-H activation, distal -C-H activation is highly challenging and has attracted significant attention in recent years. However, developments are majorly focused on Pd-based catalytic systems. In order to diversify the scope of distal -C-H functionalization, herein we disclosed the first Rh(i) catalyzed -C-H alkynylation protocol through the inverse Sonogashira coupling reaction. The protocol is compatible with various substrate classes which include phenylacetic acids, hydrocinnamic acids, 2-phenyl benzoic acids, 2-phenyl phenols, benzyl sulfonates and ether-based scaffolds. The post-synthetic modification of -alkynylated arenes is also demonstrated through DG-removal as well as functional group interconversion.
芳烃的位点选择性C-H炔基化反应以生成芳基炔烃是一种非常理想的转化反应，因为芳基炔烃在各种天然产物、药物分子和材料中广泛存在。为了确保位点选择性C-H官能团化，导向基团（DG）辅助的C-H活化已发展成为一种有用的合成工具。与DG辅助的α-C-H活化相反，远端C-H活化极具挑战性，近年来引起了广泛关注。然而，相关进展主要集中在基于钯的催化体系上。为了拓宽远端C-H官能团化的范围，在此我们通过逆Sonogashira偶联反应首次公开了Rh（I）催化的远端C-H炔基化反应方案。该方案与多种底物类型兼容，包括苯乙酸、氢化肉桂酸、2-苯基苯甲酸、2-苯基苯酚、苄基磺酸盐和醚基骨架。通过去除DG以及官能团相互转化，还展示了炔基化芳烃的合成后修饰。
