Uniting Amide Synthesis and Activation by P^III/P^V-Catalyzed Serial Condensation: Three-Component Assembly of 2-Amidopyridines

An organophosphorus (P^III/P^Vredox) catalyzed method for the three-component condensation of amines, carboxylic acids, and pyridineN-oxides to generate 2-amidopyridines via serial dehydration is reported. Whereas amide synthesis and functionalization usually occur under divergent reaction conditions, here a phosphetane catalyst (together with a mild bromenium oxidant and terminal hydrosilane reductant) is shown to drive both steps chemoselectively in an auto-tandem catalytic cascade. The ability to both prepare and functionalize amides under the action of a single organocatalytic reactive intermediate enables new possibilities for the efficient and modular preparation of medicinal targets.