Recyclable Aliphatic Nitrile-Template Enabled Remote meta-C-H Functionalization at Room Temperature

This article describes the development of a new aliphatic nitrile-template-directed remote meta-selective C-H olefin functionalization reaction of arenes. Remarkably, unlike the previous reports, this process is feasible at room temperature and enabled the formation of products with excellent regioselectivity. The present protocol encompasses a broad spectrum of substituted dihydrocinnamic acids and olefins, producing meta-C-H olefinated products (up to 96% yield). In addition, the efficacy of the present method has been showcased by the synthesis of various drug analogues (e.g., cholesterol, estrone, ibuprofen, and naproxen). Significantly, the robustness of meta-olefination was also demonstrated by gram-scale synthesis. The new nitrile-based meta-directing template, in particular, could be easily synthesized in two steps and recycled under mild conditions.

Automated summary

This article describes the development of a new aliphatic nitrile-template-directed remote meta-selective C-H olefin functionalization reaction of arenes. The method is feasible at room temperature and enables the formation of products with excellent regioselectivity. The efficacy and robustness of the method have been demonstrated through the synthesis of various drug analogues and gram-scale synthesis.