Acta Chimica Sinica ›› 2024, Vol. 82 ›› Issue (2): 132-137.DOI: 10.6023/A23090434 Previous Articles     Next Articles

Special Issue: 有机氟化学合集



黄广龙, 薛小松*()   

  1. 中国科学院上海有机化学研究所 先进氟氮材料重点实验室 上海 200032
  • 投稿日期:2023-09-30 发布日期:2023-11-29
  • 作者简介:
  • 基金资助:
    国家重点研发计划(2021YFF0701700); 国家自然科学基金(22122104); 国家自然科学基金(22193012); 国家自然科学基金(21933004); 中国科学院稳定支持基础研究领域青年团队计划(YSBR-052); 中国科学院稳定支持基础研究领域青年团队计划(YSBR-095)

Computational Study on the Mechanism of Chen’s Reagent as Trifluoromethyl Source

Guanglong Huang, Xiao-Song Xue()   

  1. Key Laboratory of Fluorine and Nitrogen Chemistry and Advanced Materials, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032
  • Received:2023-09-30 Published:2023-11-29
  • Contact: E-mail:
  • About author:
    We dedicated to this study in memory of Professor Qing-Yun Chen.
  • Supported by:
    Ministry of Science and Technology of China(2021YFF0701700); National Natural Science Foundation of China(22122104); National Natural Science Foundation of China(22193012); National Natural Science Foundation of China(21933004); CAS Project for Young Scientists in Basic Research(YSBR-052); CAS Project for Young Scientists in Basic Research(YSBR-095)

In 1989, Qing-Yun Chen’s research group at the Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences reported the development of methyl fluorosulfonyldifluoroacetate (FSO2CF2CO2Me or MFSDA) as trifluoromethylation reagent. This reagent is now known as Chen’s reagent, which is perhaps the first well-recognized and widely used trifluoromethylation reagent originate from China. Despite the widespread use of Chen’s reagent in both academia and industry, the detailed mechanism underlying the conversion of Chen’s reagent into a trifluoromethyl source has remained elusive. In this contribution, we conducted a thorough investigation into the reaction mechanism, employing density functional theory (DFT) calculations. Geometry optimizations and frequency analyses were performed using the PBE0/def2-SVP level of theory. To ensure accurate electronic energy calculations, single-point energy calculations were conducted at the ωB97X-D/def2-TZVPP level of theory. The solvent effects were considered using the solvation model density (SMD) model during both geometry optimizations and single-point energy calculations. Furthermore, Gibbs free energies were corrected with GoodVibes, employing Truhlar et al.’s quasi-harmonic treatment by setting all positive frequencies less than 100 to 100 cm–1. Concentration corrections were applied from 1 atm to 1 mol/L. Our calculations reveal the detailed mechanism governing the generation of copper(I) trifluoromethyl from Chen’s reagent in the presence of a CuI catalyst. An in-depth understanding of such mechanistic details would be helpful for future development of new reaction and application with Chen’s reagent.

Key words: density functional theory (DFT) calculation, methyl fluorosulfonyldifluoroacetate, Chen’s reagent, trifluoromethylation reagent, reaction mechanism