Direct and regioselective functionalization of remote C–H bonds in aromatic systems remains one of the foremost challenges in organic synthesis. The difficulty is sharpest when the substrate carries native functional groups that lack exogenous directing motifs, because the catalyst has no built-in handle to guide it to a specific position on the ring. Carboxylic acids are among the most synthetically versatile and pharmaceutically relevant of such groups, serving as indispensable building blocks across many disciplines, yet achieving para-C–H activation of the free acids has remained an elusive goal.

The new study reports a successful method for para-C–H activation and borylation of free aromatic carboxylic acids. According to the authors, the selectivity arises from a strategically designed iridium-based catalytic system that leverages the synergistic effect of multi-noncovalent interactions. Rather than relying on a covalently tethered directing group, the catalyst engages the substrate through several weak interactions at once, positioning the iridium center near the para C–H bond.

The method operates under mild reaction conditions, offers broad substrate scope and achieves exceptional para selectivity, the researchers state. These attributes matter practically: reactions that tolerate free carboxylic acids without prior derivatization can be applied directly to molecules that already carry the acid group, including scaffolds common in pharmaceutical chemistry.

The products of the reaction, para-borylated carboxylic acids, are described as versatile bifunctional synthons. Because the boryl group can be carried forward into further transformations while the carboxylic acid remains available for its own chemistry, the products enable sequential functionalization and streamlined access to diverse molecular scaffolds. The authors present this dual functionality as the synthetic payoff of the method.

The publication is accompanied by figures outlining the significance of carboxylic acids and prior developments in the field, the reaction development for para borylation, and the substrate scope covering substituted benzoic acids and heteroaromatic carboxylic acids. Additional figures document synthetic applications of the para-C–H activation and density functional theory computations aimed at understanding the origin of the para selectivity, along with an investigation of the para-selective borylation itself.

The computational component is notable because it addresses the central mechanistic question: why the catalyst selects the para position over other available C–H bonds.

By overcoming this longstanding challenge in C–H functionalization, the study adds a route to para-functionalized carboxylic acids and their derivatives directly from the free acids. The work was published on 27 October 2026 in Nature Catalysis by researchers including Sayan Dey, Jaitri Das, Li-Li Wang, Rong-Lin Zhong and Buddhadeb Chattopadhyay.

Subject of Research: Iridium-catalysed para-C–H activation and borylation of free aromatic carboxylic acids

Article Title: Iridium-catalysed para-C–H activation and borylation of native aromatic carboxylic acids

Article References: Dey, S., Das, J., Wang, L.-L., Zhong, R.-L., & Chattopadhyay, B. (2026). Iridium-catalysed para-C–H activation and borylation of native aromatic carboxylic acids. Nature Catalysis. https://doi.org/10.1038/s41929-026-01622-8

Image Credits: AI Generated

DOI: 10.1038/s41929-026-01622-8

Keywords: C–H activation, borylation, iridium catalysis, carboxylic acids, para selectivity, noncovalent interactions, regioselectivity, organic synthesis, Nature Catalysis, bifunctional synthons, Iridium-catalysed, para-C