Chemodivergent aminocarbonylation enabled by oxygen vacancy–engineered Pd-doped In ₂ O ₃ nanocatalysts

The amide bond is a crucial structural motif in numerous bioactive natural products and pharmaceutical compounds. Mono- (MC) and double-aminocarbonylation (DC) are key methodologies for synthesizing aryl amides, including versatile α-ketoamides. However, selectively controlling MC and DC of aryl halides has been a long-standing challenge. Here, we report a previously unknown strategy to fully invert the selectivity from MC to DC in palladium (Pd)–doped indium(III) oxide nanocatalysts by introducing oxygen vacancies (O _v ) to modulate the second-beyond coordination spheres (SBCSs) of Pd, and catalysts show excellent activity, selectivity, and reusability for synthesizing diverse amides and α-ketoamides (130 examples). SBCS modulation drives long-range electron transfer to fine-tune electron localization, elongating Pd-O bonds, and weakening their strength to promote the second carbon monoxide adsorption and insertion for the DC pathway.