Pd(II)-catalysed meta-C-H functionalizations of benzoic acid derivatives.

Abstract

Benzoic acids are highly important structural motifs in drug molecules and natural products. Selective C-H bond functionalization of benzoic acids will provide synthetically useful tools for step-economical organic synthesis. Although direct ortho-C-H functionalizations of benzoic acids or their derivatives have been intensely studied, the ability to activate meta-C-H bond of benzoic acids or their derivatives in a general manner via transition-metal catalysis has been largely unsuccessful. Although chelation-assisted meta-C-H functionalization of electron-rich arenes was reported, chelation-assisted meta-C-H activation of electron-poor arenes such as benzoic acid derivatives remains a formidable challenge. Herein, we report a general protocol for meta-C-H olefination of benzoic acid derivatives using a nitrile-based sulfonamide template. A broad range of benzoic acid derivatives are meta-selectively olefinated using molecular oxygen as the terminal oxidant. The meta-C-H acetoxylation, product of which is further transformed at the meta-position, is also reported.