Download PDF
Synlett 2015; 26(01): 127-132
DOI: 10.1055/s-0034-1378917
letter
© Georg Thieme Verlag Stuttgart · New York

A Facile and Mild Approach for Stereoselective Synthesis of α-Fluoro-α,β-unsaturated Esters from α-Fluoro-β-keto Esters via Deacylation

Jinlong Qian
School of Chemical Engineering, Nanjing University of Science & Technology, Nanjing, Jiangsu 210094, P. R. of China   Fax: +86(25)84315030   Email: yiwenbin@mail.njust.edu.cn
,
Wenbin Yi*
School of Chemical Engineering, Nanjing University of Science & Technology, Nanjing, Jiangsu 210094, P. R. of China   Fax: +86(25)84315030   Email: yiwenbin@mail.njust.edu.cn
,
Meifang Lv
School of Chemical Engineering, Nanjing University of Science & Technology, Nanjing, Jiangsu 210094, P. R. of China   Fax: +86(25)84315030   Email: yiwenbin@mail.njust.edu.cn
,
Chun Cai
School of Chemical Engineering, Nanjing University of Science & Technology, Nanjing, Jiangsu 210094, P. R. of China   Fax: +86(25)84315030   Email: yiwenbin@mail.njust.edu.cn
› Author Affiliations
Further Information

Publication History

Received: 02 August 2014

Accepted after revision: 09 October 2014

Publication Date:
05 November 2014 (online)

   Permissions and Reprints All articles of this category


Abstract

The highly stereoselective olefination reaction of α-fluoro-β-keto esters for the synthesis of α-fluoro-α,β-unsaturated esters has been developed. The olefination combines nucleophilic addition, intramolecular nucleophilic addition, and elimination in one step, as well as provides a facile synthetic approach to α-fluoro-α,β-unsaturated esters which are important units in many biologically active compounds and useful precursors in a variety of functional-group transformations.

Key words

olefination - highly stereoselective - deacylation - fluoro­olefins - carbon–carbon bond cleavage

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0034-1378917.
  • Supporting Information
 

  • References and Notes

    • 2a Van der Veken P, Kertèsz I, Senten K, Haemers A, Augustyns K. Tetrahedron Lett. 2003; 44: 6231
      CrossrefSearch in Google Scholar
    • 2b Nakamura Y, Okada M, Koura M, Tojo M, Saito A, Sato A, Taguchi T. J. Fluorine Chem. 2006; 127: 627
      CrossrefSearch in Google Scholar
    • 2c Guan T, Yoshida M, Ota D, Fukuhara T, Hara S. J. Fluorine Chem. 2005; 126: 1185
      CrossrefSearch in Google Scholar
    • 2d Pirrung MC, Han H, Ludwig RT. J. Org. Chem. 1994; 59: 2430
      CrossrefSearch in Google Scholar
    • 2e Laue KW, Mück-Lichtenfeld C, Haufe G. Tetra-hedron 1999; 55: 10413
      CrossrefSearch in Google Scholar
    • 2f Daubresse N, Chupeau Y, Francesch C, Lapierre C, Pollet B, Rolando C. Chem. Commun. 1997; 1489
    • 2g Burkhart JP, Weintraub PM, Gates CA, Resvick RJ, Vaz RJ, Friedrich D, Angelastro MR, Bey P, Peet NP. Bioorg. Med. Chem. 2002; 10: 929
      CrossrefSearch in Google Scholar
    • 2h Kaneko T, Clark R, Ohi N, Ozaki F, Kawahara T, Kamada A, Okano K, Yokohama H, Muramoto K, Arai T, Ohkuro M, Takenaka O, Sonoda J. WO 9806720, 1998
    • 2i Jaeger EP, Jurs PC, Stouch TR. E. J. Med. Chem. 1993; 28: 275
      CrossrefSearch in Google Scholar
    • 2j Honda H, Sato S, Isomae K, Ookawa J, Kuwamura T. DE 3407806, 1984
    • 2k Hibi S, Kikuchi K, Yoshimura H, Nagai M, Tagami K, Abe S, Hishinuma I, Nagakawa J, Miyamoto N. WO 9613478, 1996
    • 2l Wiedeman PE, Djuric SW, Pilushchev M, Sciotti RJ, Madar DJ, Kopecka H. US 20020115669, 2002
    • 2m Sun J, Yang Y, Huang Y. CN 103254053, 2013
    • 11a Tsuboi S, Uno T, Takeda A. Chem. Lett. 1978; 1325
    • 11b Ueno Y, Setoi H, Okawara M. Tetrahedron Lett. 1978; 39: 3753
      Search in Google Scholar
  • 12 Nakatsu S, Gubaidullin AT, Mamedov VA, Tsuboi S. Tetrahedron 2004; 60: 2337
    CrossrefSearch in Google Scholar
  • 13 Hornung CH, Hallmark B, Baumann M, Baxendale IR, Ley SV, Hester P, Clayton P, Mackley MR. Ind. Eng. Chem. Res. 2010; 49: 4576
    CrossrefSearch in Google Scholar
  • 14 Typical Experimental Procedure for the FluoroolefinsThe reaction mixture of fluorinated substrates (0.55 mmol), aldehyde (0.5 mmol), Cs2CO3 (1 mmol) and MeCN (1.5 mL) was stirred at 40 °C for the indicated time until complete consumption of the starting material, which was monitored by TLC analysis (6–12 h). The solvents were removed by rotary evaporation to provide raw products. The residue was then chromatographed on silica gel (eluent: hexane–EtOAc), affording the desired fluoroolefins.Ethyl (Z)-2-Fluoro-3-phenylacrylate (3aa)Colorless oil. 1H NMR (500 MHz, CDCl3): δ = 7.64 (d, J = 6.8 Hz, 2 H), 7.43–7.35 (m, 3 H), 6.92 (d, J = 35.2 Hz, 1 H), 4.35 (q, J = 7.1 Hz, 2 H), 1.38 (t, J = 7.1 Hz, 3 H). 19F NMR (470 MHz, CDCl3): δ = –125.31 (s). 13C NMR (126 MHz, CDCl3): δ = 160.45 (d, J = 34.3 Hz), 146.07 (d, J = 267.5 Hz), 130.20 (s), 129.30 (d, J = 7.2 Hz), 128.68 (s), 127.82 (s), 116.48 (s), 60.89 (s), 13.23 (s). MS (EI): m/z = 194.12 [M+].(Z)-2-Fluoro-1-phenyl-3-[2-(trifluoromethyl)phenyl]prop-2-en-1-one (5ar)Colorless solid. 1H NMR (500 MHz, CDCl3): δ = 8.03 (d, J = 7.9 Hz, 1 H), 7.90 (d, J = 7.6 Hz, 2 H), 7.75 (d, J = 7.9 Hz, 1 H), 7.63 (t, J = 7.5 Hz, 2 H), 7.56–7.47 (m, 3 H), 7.19 (d, J = 33.6 Hz, 1 H). 19F NMR (470 MHz, CDCl3): δ = –59.57 (s), –118.61 (s). 13C NMR (126 MHz, CDCl3): δ = 187.69 (d, J = 28.3 Hz), 154.69 (d, J = 276.2 Hz), 135.67 (s), 133.32 (s), 132.07 (s), 131.51 (d, J = 12.1 Hz), 129.47 (d, J = 3.6 Hz), 129.32 (s), 129.11 (s), 128.59 (s), 126.22 (q, J = 5.5 Hz), 124.96 (s), 122.79 (s), 115.25 (s). MS (EI): m/z = 294.15 [M+].(Z)-2-Fluoro-N-phenyl-3-[4-(trifluoromethyl)phenyl]acrylamide (5bg)Colorless solid. 1H NMR (500 MHz, DMSO): δ = 10.47 (s, 1 H), 7.90 (d, J = 8.2 Hz, 2 H), 7.80 (d, J = 8.3 Hz, 2 H), 7.74 (d, J = 7.7 Hz, 2 H), 7.35 (t, J = 7.9 Hz, 2 H), 7.20–7.07 (m, 2 H). 19F NMR (470 MHz, DMSO): δ = –61.30 (s), –121.52 (s). 13C NMR (126 MHz, DMSO): δ = 157.26 (d, J = 29.8 Hz), 50.89 (d, J = 281.5 Hz), 137.26 (s), 134.70 (s), 129.89 (d, J = 6.0 Hz), 128.52 (d, J = 32.1 Hz), 128.18 (s), 125.22 (s), 24.04 (s), 120.38 (s), 111.49 (s). MS (EI): m/z = 309.10 [M+].