High-Pressure Promoted Nazarov-like Electrocyclization Enables Access to trans-4,5-Diamino-cyclopent-2-enones Bearing Electron-Poor Anilines

Abstract

Unlike secondary alkyl amines and electron-rich anilines, secondary electron-poor anilines are challenging amine sources to explore the chemical space of Lewis acid-catalyzed condensation-based transformations with furfural. In this work, we report the efficient synthesis of trans-4,5-diamino cyclopentenones (DCP) using a high-pressure promoted Nazarov-like electrocyclization of Stenhouse salts arising from the Sc(III)-catalyzed condensation of furfural with secondary electron-poor anilines. The reaction enables access to otherwise difficult-to-access DCP and compatibility with a large scope of alkyl and aryl secondary amines. A 2-to 18-fold increase in yields for electron-poor anilines was highlighted using this approach in the synthesis of a pharmacologically active compound.