Synthesis of structurally diverse thiazole-fused indole derivatives via a one-pot four-component cascade reaction.

An efficient, four-component strategy for the synthesis of multifunctionalized thiazole-fused indole derivatives under mild conditions has been established. The acid-catalyzed four-component cascade reactions were conducted by reacting inexpensive and readily available 2-methylbenzo[d]thiazol-5/6-amine, 2,2-dihydroxy-1-arylethan-1-one, Meldrum’s acid, and alcohol or amine in refluxing acetonitrile. A total of 30 examples were studied, and the results revealed a broad substrate scope and moderate to good yields (42–76%). A reaction mechanism involving Knoevenagel condensation, Michael addition, enamine-imine transformation, and amine hydrolysis of esters has been proposed to explain the transformation processes. The advantages of the present strategy include an effective one-pot four-component strategy, mild reaction conditions, structurally diverse thiazole-fused indole derivatives, and the absence of metal promoters.