2-Arylacetamides as Versatile Precursors for 3-Aminoisocoumarin and Homophthalimide Derivatives: Palladium-Catalyzed Cascade Double Carbonylation Reactions

The synthesis of biologically relevant homophthalimide and 3-aminoisocoumarin nuclei via palladium-catalyzed carbonylation of 2-(2-iodoaryl) acetamides has been developed. The degree of N-substitution on the starting amide substrate dictates whether C-N or C-O coupling takes place in the final step of the catalytic cycle giving rise to each type of heterocycle. The introduction of a second C-halogen bond in the starting acetamides allows a catalytic cascade double carbonylation involving a C-H activation step to give fused heterocyclic structures.