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

Abstract

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. © 2022 the royal society of chemistry