Synthesis of Quinolines and Tetrahydroquinolines From Aromatic Propargylamines via Activator‐Free Gold Catalysis in Hexafluoroisopropanol

The quinoline/tetrahydroquinoline scaffold is ubiquitous in natural products and commercial drugs; therefore, several synthetic methods have been developed to provide access to such structures. However, many of these established protocols rely on external activators or additives, relatively high catalyst loadings, and experimentally demanding setups, limiting their practicality and scalability. In this study, a user‐friendly, gold‐catalyzed, silver‐, and additive‐ free protocol is reported for the cycloisomerization of aromatic propargylamines towards quinoline and tetrahydroquinoline derivatives, by employing hexafluoroisopropanol (HFIP) as both solvent and activator. HFIP can activate the catalytically inert Au(I)‐Cl complexes through hydrogen bonding, obviating the use of silver salts or other external additives, while also acting as a recyclable solvent. This simple activation mode, combined with a robust N‐heterocyclic carbene (NHC) gold catalyst, enables high catalytic efficiency at low catalyst loadings and with a broad substrate scope under mild conditions. The methodology provides access to, among others, complex phenanthrolines and biquinolines, enhancing the toolbox for N‐ heterocycle synthesis. This method further allows selective access to either quinolines or tetrahydroquinolines, through the controlled addition of a Hantzsch ester as hydride donor. Mechanistic studies permit the observation of a key intermediate, shedding light on the reaction mechanism and the crucial role of HFIP in the catalyst activation and proton transfer steps.