Download PDF
Synthesis 2021; 53(13): 2293-2303
DOI: 10.1055/a-1395-4788
paper

Efficient Monofluoroalkylation of Thiophenols or Phenols with α-Bromo-α-Fluoroketones under Mild Conditions

Zhi Li
a   Shanghai Engineering Research Center of Green Fluoropharmaceutical Technology, Shanghai Institute of Technology, Shanghai 201418, P. R. of China
,
Mougui Fang
a   Shanghai Engineering Research Center of Green Fluoropharmaceutical Technology, Shanghai Institute of Technology, Shanghai 201418, P. R. of China
,
Jingjing Wu∗
a   Shanghai Engineering Research Center of Green Fluoropharmaceutical Technology, Shanghai Institute of Technology, Shanghai 201418, P. R. of China
b   Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R. of China
,
Yunli Liu
a   Shanghai Engineering Research Center of Green Fluoropharmaceutical Technology, Shanghai Institute of Technology, Shanghai 201418, P. R. of China
,
Yecheng Liu
a   Shanghai Engineering Research Center of Green Fluoropharmaceutical Technology, Shanghai Institute of Technology, Shanghai 201418, P. R. of China
,
Fanhong Wu∗
a   Shanghai Engineering Research Center of Green Fluoropharmaceutical Technology, Shanghai Institute of Technology, Shanghai 201418, P. R. of China
› Author AffiliationsWe are grateful for financial support from the National Natural Science Foundation of China (Grant Nos. 21672151 and 21602136).
› Further Information
    Permissions and Reprints All articles of this category


Abstract

An efficient nucleophilic substitution reaction between α-bromo-α-fluoroketones and thiophenols or phenols is reported for the synthesis of α-fluoro-β-ketosulfides or α-fluoro-β-ketone ethers in yields ranging from 78–93%. This method exhibits good functional group tolerance and a broad scope of nucleophilic substrates, including natural phenolic compounds.

Key words

monofluoroalkyltion - nucleophilic substitution - α-bromo-α-fluoroketones - α-fluoro-β-ketosulfides - α-fluoro-β-ketone ethers

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-1395-4788.
  • Supporting Information


Publication History

Received: 28 December 2020

Accepted after revision: 18 February 2021

Accepted Manuscript online:
18 February 2021

Article published online:
04 March 2021

© 2021. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

    • 1a Müller K, Faeh C, Diederich F. Science 2007; 317: 1881
      CrossrefPubMed
    • 1b Hagmann WK. J. Med. Chem. 2008; 51: 4359
      CrossrefPubMed
    • 1c Shimizu M, Hiyama T. Angew. Chem. Int. Ed. 2005; 117: 218
      Crossref
    • 1d O’Hagan D. Chem. Soc. Rev. 2008; 37: 308
      CrossrefPubMed
    • 1e Bégué JP, Delpon DB. Bioorganic and Medicinal Chemistry of Fluorine . John Wiley & Sons; Hoboken: 2008
      Google Scholar
    • 2a Erickson JA, McLoughlin JI. J. Org. Chem. 1995; 60: 1626
      Crossref
    • 2b Aráoz R, Anhalt E, René L, Denisot MA. B, Courvalin P, Badet B. Biochemistry 2000; 39: 15971
      CrossrefPubMed
    • 2c Romanenko VD, Kukhar VP. Chem. Rev. 2006; 106: 3868
      CrossrefPubMed
    • 2d Wang J, Liu H. Chin. J. Org. Chem. 2011; 31: 1785
    • 2e Wang J, Roselló MS, Aceña JL, del Pozo C, Sorochinsky AE, Fustero S, Soloshonok VA, Liu H. Chem. Rev. 2014; 114: 2432
      CrossrefPubMed
    • 3a Ni C, Hu M, Hu J. Chem. Rev. 2015; 115: 765
      CrossrefPubMed
    • 3b Xu XH, Matsuzaki K, Shibata N. Chem. Rev. 2015; 115: 731
      CrossrefPubMed
    • 3c Boyer J, Arnoult E, Medebielle M, Guillemont J, Unge J, Jochmans D. J. Med. Chem. 2011; 54: 7974
      CrossrefPubMed
    • 4a Hansch C, Leo A, Unger SH, Kim KH, Nikaitani D, Lien EJ. J. Med. Chem. 1973; 16: 1207
      CrossrefPubMed
    • 4b Hansch C, Leo A, Taft RW. Chem. Rev. 1991; 91: 165
      Crossref
    • 4c Leroux F, Jeschke P, Schlosser M. Chem. Rev. 2005; 105: 827
      CrossrefPubMed
    • 4d Jeschke P, Baston E, Leroux FR. Mini-Rev. Med. Chem. 2007; 7: 1027
      CrossrefPubMed
  • 6 Helmich KE, Pereira JH, Gall DL, Heins RA, McAndrew RP, Bingman C, Deng K, Holland KC, Noguera DR, Simmons BA, Sale KL, Ralph J, Donohue TJ, Adams PD, Phillips GN. J. Biol. Chem. 2015; 291: 5234
    CrossrefPubMed
  • 7 Fluorine in Medicinal Chemistry and Chemical Biology. Ojima I. John Wiley & Sons; Chichester: 2009
    CrossrefGoogle Scholar
  • 8 Karagas MR, Cushing GL. Jr, Greenberg ER, Mott LA, Spencer SK, Nierenberg DW. Br. J. Cancer 2001; 85: 683
    CrossrefPubMed
  • 9 Khouzani HL, Poorheravi MR, Sadeghi MM, Caggiano L, Jackson RF. W. Tetrahedron 2008; 64: 7419
    Crossref
  • 10 Hara S, Monoi M, Umemura R, Fuse C. Tetrahedron 2012; 68: 10145
    Crossref
  • 11 Varun BV, Prabhu KR. J. Org. Chem. 2017; 82: 9525
    CrossrefPubMed
  • 12 Yuan WM, Eriksson L, Szabó KJ. Angew. Chem. Int. Ed. 2016; 55: 1
    Crossref
  • 13 Liang JQ, Han J, Wu JJ, Wu PJ, Hu J, Hu F, Wu FH. Org. Lett. 2019; 21: 6844
    CrossrefPubMed