Work

Hexafluoroisopropylthiolation of Ene‐yne‐ketones with HFA · 3H 2 O / SOCl 2 for Modular Synthesis of SCH ( CF 3 ) 2 ‐Functionalized Furans

Year: 2026

Type: article

Abstract: Comprehensive Summary Notwithstanding the importance of the hexafluoroisopropyl group (CH(CF 3 ) 2 ) in medicinal and agricultural chemistry, convenient access to hexafluoroisopropylthiolated (SCH(CF 3 ) 2 ) compounds remains challenging, limiting their exploration. Herein, we report a straightforward and efficient hexafluoroisopropylthiolation strategy using readily available hexafluoroacetone trihydrate (HFA·3H 2 O) and SOCl 2 as practical reagents. This one‐pot process leverages SOCl 2 in a dual role as both an unconventional sulfur surrogate and a dehydrating agent, overcoming the inherent inertness of the hydrate and enabling in situ generation of hexafluoroisopropyl polysulfide intermediates as the actual SCH(CF 3 ) 2 sources. Thereby, these intermediates serve as SCH(CF 3 ) 2 anion precursors to undergo Pd(II)‐ or Ni(II)‐catalyzed carbene cyclization with ene‐yne‐ketones, efficiently furnishing structurally diverse SCH(CF 3 ) 2 ‐functionalized furans. Several products exhibited superior inhibitory activity against three human cancer cell lines over 5‐fluorouracil. Notably, compound 25 effectively induced late apoptosis in MDA‐MB‐231 cells by elevating intracellular ROS levels.

Source: Chinese Journal of Chemistry

DOI: 10.1002/cjoc.70793