Pd-catalyzed regioselective synthesis of 3-aminoindoles via Larock-type annulation of N-protected 2-iodoanilines with ynamides.

A Pd-catalyzed Larock-type annulation of N-protected 2-iodoanilines with ynamides has been developed for the regioselective synthesis of 3-aminoindoles under mild conditions using commercially available PdCl2(PPh3)2. This concise one-pot protocol delivers a diverse array of 3-aminoindoles in good to excellent yields with broad functional-group tolerance for both coupling partners. Notably, the N-acetyl group on the aniline substrate plays a dual role: it directs C3 regioselectivity and acts as a masked amino surrogate, thus avoiding the need for external amination reagents. Gram-scale synthesis and post-synthetic transformations further validate the synthetic utility. This work provides a practical and regioselective platform for constructing 3-aminoindoles from readily available starting materials.