Pd-Catalyzed Facile and Selective B–H Carbonylation Leading to Boron Cluster Carboxylic Acids for Diverse Transformations

The incorporation of a carbonyl group into a chemical scaffold represents a pivotal strategy in drug design and material synthesis. A synthetic challenge, however, has been the introduction of carbonyls into carborane clusters at the boron sites due to the inherent inertness of the B–H bonds and the difficulty in controlling site selectivity. Here, we report a palladium-catalyzed approach for the selective and straightforward carboxylation of o-, m-, and p -carboranes with carbon monoxide (CO) at ambient temperature and pressure, generating boron-substituted carborane-based carboxylates. Experimental and computational studies reveal that CO plays a dual role as a carbonylation source and a π-acid ligand, which enhances the electrophilicity of the palladium center, leading to improved regioselectivity and reduced barrier for the key B–H bond activation. The reaction exhibits excellent site selectivity, atom economy, step economy, and broad substrate scope. Importantly, carboxylate functionality can serve as a versatile platform for carborane functionalization, including methylation, cyanation, isocyanation, arylation, fluorination, azidation, and borylation. Furthermore, the conjugation of a carborane moiety with a drug scaffold or bioactive molecule has been realized via ester, thioester, and amide formation. Our methods provide access to valuable, or even previously inaccessible, functionalized carboranes, surpassing traditional methods that rely on halogenated carborane precursors.