Directing group assisted rhodium catalyzed meta-C-H alkynylation of arenes

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 ortho-C-H activation, distal meta-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 meta-C-H functionalization, herein we disclosed the first Rh(i) catalyzed meta-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 meta-alkynylated arenes is also demonstrated through DG-removal as well as functional group interconversion.

Automated summary

Site-selective C-H alkynylation of arenes is highly desirable for the synthesis of natural products, drug molecules, and materials. In this study, we developed a Rh(I)-catalyzed protocol for meta-C-H alkynylation, which broadens the scope of this transformation and allows for post-synthetic modifications.