Mechanistic elucidation of HFIP ‐enabled C–Cl bond activation in the synthesis of tetrahydroquinoline derivatives
Year: 2026
Type: article
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.
DOI: 10.1002/bkcs.70162
Authors: Seung Hoon Lee, Hyung Min Chi
Institution: Pohang University of Science and Technology
Language: English
Topic: Chemical Reaction Mechanisms
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $3,470
OpenAlex ID: W7151341130