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Synlett 2010(5): 830-834  
DOI: 10.1055/s-0029-1219199
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Fluorine-Containing Furan Derivatives from the Michael Addition of Ethyl 4,4,4-Trifluoro-3-oxobutanoate with β-Nitrostyrenes

Liping Song*a,b, Xianfu Lia, Chunhui Xingb, Dongmei Lia, Shizheng Zhu*b, Hongmei Dengc, Min Shaoc
a Department of Chemistry, School of Science, Shanghai University, No. 99, Shangda Road, Shanghai 200444, P. R. of China
Fax: +86(21)66132797; e-Mail: lpsong@shu.edu.cn;
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, P. R. of China
c Instrumental Analysis and Research Center, Shanghai University, Shanghai 200444, P. R. of China
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Publication History

Received 28 October 2009
Publication Date:
14 January 2010 (online)

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Abstract

Ethyl 4,4,4-trifluoro-3-oxobutanoate reacted with nitrostyrenes in the presence of Et3N to afford ethyl 5-(hydroxyim­ino)-4-aryl-2-(trifluoromethyl)-2,5-dihydrofuran-3-carboxylates along with a small amount of ethyl 2-hydroxy-5-imino-4-aryl-2-(trifluoromethyl)-2,5-dihydrofuran-3-carboxylates. Treatment of ethyl 5-(hydroxyimino)-4-aryl-2-(trifluoromethyl)-2,5-dihydro­furan-3-car­boxylates with 1.2 equivalents of TsOH in t-BuOH, afforded ethyl 2-hydroxy-5-imino-4-aryl-2-(trifluoromethyl)-2,5-dihydrofuran-3-carboxylates in good yields. However, ethyl 2-ethoxy or methoxy-5-oxo-4-aryl-2-(trifluoromethyl)-2,5-dihydrofuran-3-carboxylates were obtained as major products in EtOH or MeOH along with a small amount of ethyl 2-hydroxy-5-imino-4-aryl-2-(trifluoromethyl)-2,5-dihydrofuran-3-carboxylates.

Key words

Michael addition - cyclization - fluorine-containing furans - 4,4,4-trifluoro-3-oxobutanone - β-nitro-stryene

    References and Notes

  • 1 Perlmuter P. In Conjugate Addition Reaction in Organic Synthesis   Pergamon; Oxford: 1992. 
    Google Scholar
  • 2a The Nitro Group in Organic Synthesis   One N. Wiley-VCH; New York: 2001. 
    Google Scholar
  • 2b Nef JU. Justus Liebigs Ann. Chem.  1984,  280 
    Google Scholar
  • 2c Ghosh AK. Bilcer G. Schiltz G. Synthesis  2001,  2203 
    Google Scholar
  • 2d Ballini R. Petrini M. Tetrahedron  2004,  60:  1017 
    Google Scholar
  • 3a Wang W. Wang J. Li H. Angew. Chem. Int. Ed.  2005,  44:  1369 
    Google Scholar
  • 3b Mendler B. Kazmaier U. Huch V. Veith M. Org. Lett.  2005,  7:  2643 
    Google Scholar
  • 3c Ji J. Barnes DM. Zhang J. King SA. Wittenberger SJ. Morton HE. J. Am. Chem. Soc.  1999,  121:  10215 
    Google Scholar
  • 3d Barnes DM. Ji J. Fickes MG. Fitzgerald MA. King SA. Morton HE. Plagge FA. Preskill M. Wittenberger SJ. Zhang J.
    J. Am. Chem. Soc.  2002,  124:  13097 
    Google Scholar
  • 3e Evans DA. Seidel D. J. Am. Chem. Soc.  2005,  127:  9985 
    Google Scholar
  • 4a Ansell GB. Moore DW. Nielsen AT. Chem. Comm.  1970,  1602 
    Google Scholar
  • 4b Ansell GB. Moore DW. Nielsen AT. J. Chem. Soc. B  1971,  2376 
    Google Scholar
  • 5a Boerg F. Schutze GR. Chem. Ber.  1957,  90:  1215 
    Google Scholar
  • 5b Yanami T. Ballatore A. Miyashita M. Kato M. Yoshikoshi A. J. Chem. Soc., Perkin Trans. 1  1978,  1144 
    Google Scholar
  • 6 Ishikawa T. Miyahara T. Asakura M. Higuchi S. Org. Lett.  2005,  7:  1211 
    CrossrefGoogle Scholar
  • 7 Bégué JP. Bonnet-Delpon D. Dogbeavou A. J. Fluorine Chem.  1999,  54:  278 
    CrossrefGoogle Scholar
  • 8a Organofluorine Compounds. Chemistry and Applications   Hiyama T. Springer; New York: 2000. 
    Google Scholar
  • 8b Organofluorine Chemistry: Principles and Commercial Applications   Banks RE. Smart BE. Tatlow JC. Plenum Press; New York: 1994. 
    Google Scholar
  • 8c Fluorine in Bioorganic Chemistry   Welch JT. Eshwarakrishman S. Wiley; New York: 1991. 
    Google Scholar
  • 8d Fluorine-Containing Molecules. Structure, Reactivity, Synthesis, and Applications   Liebman JF. Greenberg A. Dolbier WR. VCH; Weinheim: 1988. 
    Google Scholar
  • 9a Li XF. Song LP. Xing CH. Zhao JW. Zhu SZ. Tetrahedron  2006,  62:  2255 
    Google Scholar
  • 9b Li DM. Song LP. Li XF. Xing CH. Peng WM. Zhu SZ. Eur. J. Org. Chem.  2007,  3520 
    Google Scholar
  • 9c Li DM. Song LP. Song SD. Zhu SZ. J. Fluorine Chem.  2007,  128:  952 
    Google Scholar
  • 9d Song SD. Song LP. Dai BF. Yi H. Jin GF. Zhu SZ. Shao M. Tetrahedron  2008,  64:  5728 
    Google Scholar
  • 9e Dai BF. Song LP. Wang PY. Yi H. Cao WG. Jin GF. Zhu SZ. Shao M. Synlett  2009,  1842 
    Google Scholar
  • 14a Connolly JD. Hill RA. Dictionary of Terpenoids   Vol. 1:  Chapman and Hall; London: 1991.  p.476-541  
    Google Scholar
  • 14b Koch SSC. Chamberlin AR. J. Org. Chem.  1993,  58:  2725 ; and references therein
    Google Scholar
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General Procedures for the Reaction of 1 with 2
To a 10 mL round-bottom flask containing ethyl 4,4,4-trifluoro-3-oxobutanoate 1 (368.0 mg, 2.0 mmol)was added DME (3.0 mL), 2a (298.0 mg, 2.0 mmol), and Et3N (0.4 mmol). The resulting mixture was stirred at refluxing temperature. After stirring for 4.5 h, the TLC analysis showed that the reaction was finished. The solvent was evaporated, and the residue was purified by column chromatography on a silica gel using PE-EtOAc (5:1, v/v) as eluent to afford 3a (523.0 mg, 83%) along with a small amount of 4a (31.0 mg, 5%).

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Spectroscopic Data for Products 3 and 4
Compound 3a: colorless solid; mp 129-130 ˚C. ¹H NMR (300 MHz, CDCl3): δ = 1.18 (t, J = 7.2 Hz, 3 H), 4.17 (qd, J = 7.2 Hz, J AB = 10.8 Hz, 1 H), 4.25 (qd, J = 7.2 Hz, J AB = 10.8 Hz, 1 H), 5.80 (q, ³ J H-F = 5.1 Hz, 1 H), 7.13 (br, 1 H), 7.42-7.51 (m, 5 H). ¹³C NMR (75.5 MHz, CDCl3): δ = 13.6, 62.0, 82.4 (q, ² J C-F = 34.6 Hz), 121.9 (q, ¹ J C-F = 282.0 Hz), 127.3, 128.1, 129.4, 130.3, 130.4, 143.4, 158.8, 160.7. ¹9F NMR (282 MHz, CDCl3): δ = -76.52 (d, ³ J H-F = 5.1 Hz, 3 F). IR (KBr): 3412, 2986, 2917, 1720, 1662, 1497, 1252, 1151, 1003, 935, 692 cm-¹. MS (70 eV, EI): m/z (%) = 315 (100) [M+], 270 (38.8) [M - OEt]+, 246 (52.3) [M - CF3]+, 69 (7.5) [CF3 +]. Anal. Calcd for C14H12F3NO4: C, 53.33; H, 3.81; N, 4.44. Found: C, 53.45; H, 3.85; N, 4.30.
Compound 4a: colorless solid; mp 110-112 ˚C. ¹H NMR (300 MHz, CDCl3): δ = 1.21 (t, J = 7.2 Hz, 3 H), 4.30 (q, J = 7.2 Hz, 2 H), 5.50 (s, 1 H), 6.84 (s, 1 H), 7.26-7.54 (m, 5 H). ¹9F NMR (282 MHz, CDCl3): δ = -80.58 (s, 3 F). IR (KBr): 3318, 2987, 1728, 1645, 1197, 1069, 733, 695 cm-¹. MS (70 eV, EI): m/z (%) = 315 (3.6) [M+], 270 (4.3) [M - OEt]+, 246 (34.4) [M - CF3]+, 200(100) [M - CF3 - EtOH]+, 69 (6.0) [CF3 +]. Anal. Calcd for C14H12F3NO4: C, 53.33; H, 3.81, N, 4.44. Found: C, 53.72; H, 3.95; N, 4.10.

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CCDC 292367 contains the supplementary crystallographic data. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: +44 (1223)336033.

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General Experimental Procedure for the Transformation of 3 to 4 and 5
Reflux the solution of 3 (0.5 mmol), in ROH (3.0 mL) with 1.2 equiv (0.6 mmol, 103.0 mg) of TsOH for ca. 4 h, TLC showed that 3 was completely transformed into 4 and 5 in different ratios, which were correlated with the size of R in the ROH. Compounds 4 and 5 were separated and purified by column chromatography on a silica gel using PE-EtOAc (10:1, v/v) as eluent.

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Spectroscopic Data for Products 5
Compound 5a: colorless solid; mp 49-50 ˚C. ¹H NMR (300 MHz, CDCl3): δ = 1.26 (t, J = 7.2 Hz, 3 H), 1.34 (t, J = 7.2 Hz, 3 H), 3.74 (qd, J = 7.2 Hz, J AB = 8.4 Hz, 1 H), 3.83 (qd, J = 7.2 Hz, J AB = 8.4 Hz, 1 H), 4.34 (q, J = 7.2 Hz, 2 H), 7.43-7.51 (m, 3 H), 7.62-7.65 (m, 2 H). ¹³C NMR (75.5 MHz, CDCl3): δ = 13.6, 14.6, 61.3, 62.7, 102.6 (q, ² J C-F = 35.6 Hz), 120.5 (q, ¹ J C-F = 286.1 Hz), 126.8, 128.7, 129.0, 131.2, 137.9, 141.0, 161.4, 166.3. ¹9F NMR (282 MHz, CDCl3): δ = -80.51 (s, 3 F). IR (KBr): 2988, 1797, 1736, 1657, 1448, 1226, 1196 cm-¹. MS (70 eV, EI): m/z (%) = 344 (1.8) [M+], 299 (11.0) [M - OEt]+, 275 (27.9) [M - CF3]+, 201 (64.3) [M - OEt - Et - CF3]+, 69 (9.2) [CF3 +]. Anal. Calcd for C16H15F3O5: C, 55.81; H, 4.36. Found: C, 55.93; H, 4.41.