Isoxazoles to Multisubstituted Thiazoles via an Ammonium Iodide-Catalyzed Formal [3+2] Cycloaddition Reaction

A method for the conversion of isoxazoles into thiazoles by skeleton rearrangement has been achieved by an ammonium iodide-catalyzed cycloaddition protocol under mild conditions with a broad substrate scope and good functional group tolerance. Most appealingly, the reaction can proceed smoothly without the addition of any transition metal catalyst. Detailed mechanistic studies, including control experiments and key reaction intermediate characterization, reveal an intermolecular [3+2] cycloaddition reaction pathway. We also demonstrated the synthetic utility on a preparative-scale trisubstituted thiazole for diverse downstream transformations, including the synthesis of several bioactive molecules.