A general synthesis of tetrahydropyrazolo[3,4-d]thiazoles

A short three-step synthesis of tetrasubstituted 3,3a,5,6-tetrahydro-2H-pyrazolo[3,4-d]thiazoles has been worked out. This relatively unknown heterobicyclic system is assembled from two carbonyl compounds, an amine, a hydrazine, and mercaptoacetic acid ester. These versatile starting materials allow the introduction of a broad range of alkyl, haloalkyl, cycloalkyl, aryl, and heteroaryl substituents into four different positions of the bicyclic scaffold. The efficiency of the synthesis route is proven by the fact, that two of the three steps are a multicomponent reaction or a cascade reaction, respectively, and that it can further be shortened to two consecutive one-pot processes.