Sc(OTf)3‑Catalyzed Iodocyclization/Ritter-Type Amidation of N‑Alkoxypropiolamides: A Synthetic Strategy for Isoxazol-3(2H)‑ones

A Sc­(OTf)3-catalyzed iodocyclization/Ritter-type amidation of N-alkoxypropiolamides for the synthesis of 4-iodoisoxazol-3­(2H)-ones bearing an amide group has been developed. This domino protocol allows the construction of a valuable heterocycle, isoxazol-3­(2H)-one, as well as the introduction of two functional groups. The reaction has a broad substrate scope and can be carried out on a large scale. Control experiments suggest that Sc­(OTf)3 acts as a dual activator for both the iodocyclization and amidation steps. In addition, the N-alkoxy group in the substrate suppresses some of the side reactions.