Mechanistic elucidation of <scp>HFIP</scp> ‐enabled C–Cl bond activation in the synthesis of tetrahydroquinoline derivatives

Abstract Hexafluoroisopropanol (HFIP) is a powerful reaction medium that enables transformations involving cationic intermediates, yet the mechanistic basis of its reactivity remains incompletely understood. Herein, we report a mechanistic investigation of the HFIP‐mediated transformation of propargylic halides with anilines, affording tetrahydroquinolines through a cascade sequence. Systematic studies reveal that HFIP promotes ionization of propargylic chlorides by stabilizing ion pairs and enhancing effective Brønsted acidity. Reaction efficiency is governed by a balance between productive ionization and substrate decomposition, and deuterium‐labeling experiments establish that HFIP participates directly in proton transfer during the disproportionation step. These findings provide a unified mechanistic framework for HFIP‐enabled C–Cl activation and highlight the potential of highly ionizing solvent systems in bond activation and cascade transformations.