Calcium-Mechanochemistry Enabled Ketone Synthesis From Organic Iodides and Carboxylic Acids

Organocalcium reagents possess a reactivity profile distinct from that of classical organolithium and Grignard reagents, yet their synthetic potential remains underexplored. Here we report that mechanochemically generated organocalcium species exhibit an unusual chemoselectivity toward carboxylate salts, enabling the direct and selective transformation of carboxylates into ketones without overaddition, a persistent limitation of conventional organometallic chemistry. Commercially available calcium metal is directly activated by ball milling with aryl iodides to generate reactive organocalcium intermediates under solvent-minimized and ambient conditions. This protocol exhibits broad substrate scope, excellent chemoselectivity, and high functional-group tolerance. Moreover, the reaction can be extended to the direct use of carboxylic acids, enabling a one-step synthesis of pharmaceutically and industrially relevant ketones.