A Multicomponent Approach to Imidazo[2,1-b]thiazole Derivatives by Sequential PdI2/KI-Catalyzed Deprotective Oxidative Aminocarbonylation - Dearomative Cyclization - Aromatization

We report a direct, multicomponent approach to an important class of fused-ring heterocycles, namely, imidazo[2,1-b]thiazole derivatives starting from simple and readily available building blocks (N-Boc-N-propargylthiazol-2-amines, carbon monoxide, a secondary amine, and oxygen). The process takes place under the catalysis of the simple PdI2/KI system under relatively mild conditions (100 degrees C under 20 atm of a 4 : 1 mixture of CO-air), and leads to 2-(imidazo[2,1-b]thiazol-5-yl)-N,N-dialkylacetamides in yields up to 87 %. The mechanistic pathway leading to carbonylated imidazo[2,1-b]thiazole occurs through an ordered sequence of steps, involving amine-induced N-deprotection, oxidative aminocarbonylation of the triple bond (with Csp-H activation and formation of a 2-ynamide intermediate), dearomative cyclization (by intramolecular conjugate addition of thioazolic nitrogen to the 2-ynamide moiety) and aromatization by proton-shift isomerization. When starting from N-Boc-N-(propargyl)benzo[d]thiazol-2-amine, tricyclic benzimidazothiazoles were formed in moderate yields.