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