Synthesis and characterization of steroidal, anellated aminothiophenes by Gewald reaction

Gewald 3-component reactions (G-3CR), i.e., reactions of a carbonyl compound with an activated nitrile in the presence of a secondary amine and sulfur, lead straightforwardly to anellated 2-aminothiophenes. Interestingly, their application to steroidal hydrocarbons has been limited to a single example. We could show in this work that Gewald 3-component reactions can be performed successfully for molecules holding a cholesterol or sitostanol skeleton, such as 5a-cholestan3-one (8) and 5a-sitostan-3-one (11), thus leading in good yields to the corresponding anellated steroidal 2-amino-thiophenes 12-15. Gewald reaction proved to be an excellent method to access heterocyclic steroids.