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

Liping Song; Xianfu Li; Chunhui Xing; Dongmei Li; Shizheng Zhu; Hongmei Deng; Min Shao

doi:10.1055/s-0029-1219199

LETTER

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

Liping Song*^a,b, Xianfu Li^a, Chunhui Xing^b, Dongmei Li^a, Shizheng Zhu*^b, Hongmei Deng^c, Min Shao^c
^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

Abstract

All articles of this category

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

Full Text

References

References and Notes

<A NAME="RW17309ST-1">1</A> Perlmuter P. In Conjugate Addition Reaction in Organic Synthesis Pergamon; Oxford: 1992.

<A NAME="RW17309ST-2A">2a</A> The Nitro Group in Organic Synthesis One N. Wiley-VCH; New York: 2001.

<A NAME="RW17309ST-2B">2b</A> Nef JU. Justus Liebigs Ann. Chem. 1984, 280

<A NAME="RW17309ST-2C">2c</A> Ghosh AK. Bilcer G. Schiltz G. Synthesis 2001, 2203

<A NAME="RW17309ST-2D">2d</A> Ballini R. Petrini M. Tetrahedron 2004, 60: 1017

<A NAME="RW17309ST-3A">3a</A> Wang W. Wang J. Li H. Angew. Chem. Int. Ed. 2005, 44: 1369

<A NAME="RW17309ST-3B">3b</A> Mendler B. Kazmaier U. Huch V. Veith M. Org. Lett. 2005, 7: 2643

<A NAME="RW17309ST-3C">3c</A> Ji J. Barnes DM. Zhang J. King SA. Wittenberger SJ. Morton HE. J. Am. Chem. Soc. 1999, 121: 10215

<A NAME="RW17309ST-3D">3d</A> 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

<A NAME="RW17309ST-3E">3e</A> Evans DA. Seidel D. J. Am. Chem. Soc. 2005, 127: 9985

<A NAME="RW17309ST-4A">4a</A> Ansell GB. Moore DW. Nielsen AT. Chem. Comm. 1970, 1602

<A NAME="RW17309ST-4B">4b</A> Ansell GB. Moore DW. Nielsen AT. J. Chem. Soc. B 1971, 2376

<A NAME="RW17309ST-5A">5a</A> Boerg F. Schutze GR. Chem. Ber. 1957, 90: 1215

<A NAME="RW17309ST-5B">5b</A> Yanami T. Ballatore A. Miyashita M. Kato M. Yoshikoshi A. J. Chem. Soc., Perkin Trans. 1 1978, 1144

<A NAME="RW17309ST-6">6</A> Ishikawa T. Miyahara T. Asakura M. Higuchi S. Org. Lett. 2005, 7: 1211

<A NAME="RW17309ST-7">7</A> Bégué JP. Bonnet-Delpon D. Dogbeavou A. J. Fluorine Chem. 1999, 54: 278

<A NAME="RW17309ST-8A">8a</A> Organofluorine Compounds. Chemistry and Applications Hiyama T. Springer; New York: 2000.

<A NAME="RW17309ST-8B">8b</A> Organofluorine Chemistry: Principles and Commercial Applications Banks RE. Smart BE. Tatlow JC. Plenum Press; New York: 1994.

<A NAME="RW17309ST-8C">8c</A> Fluorine in Bioorganic Chemistry Welch JT. Eshwarakrishman S. Wiley; New York: 1991.

<A NAME="RW17309ST-8D">8d</A> Fluorine-Containing Molecules. Structure, Reactivity, Synthesis, and Applications Liebman JF. Greenberg A. Dolbier WR. VCH; Weinheim: 1988.

<A NAME="RW17309ST-9A">9a</A> Li XF. Song LP. Xing CH. Zhao JW. Zhu SZ. Tetrahedron 2006, 62: 2255

<A NAME="RW17309ST-9B">9b</A> Li DM. Song LP. Li XF. Xing CH. Peng WM. Zhu SZ. Eur. J. Org. Chem. 2007, 3520

<A NAME="RW17309ST-9C">9c</A> Li DM. Song LP. Song SD. Zhu SZ. J. Fluorine Chem. 2007, 128: 952

<A NAME="RW17309ST-9D">9d</A> Song SD. Song LP. Dai BF. Yi H. Jin GF. Zhu SZ. Shao M. Tetrahedron 2008, 64: 5728

<A NAME="RW17309ST-9E">9e</A> Dai BF. Song LP. Wang PY. Yi H. Cao WG. Jin GF. Zhu SZ. Shao M. Synlett 2009, 1842

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%).

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.

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.

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.

<A NAME="RW17309ST-14A">14a</A> Connolly JD. Hill RA. Dictionary of Terpenoids Vol. 1: Chapman and Hall; London: 1991. p.476-541

<A NAME="RW17309ST-14B">14b</A> Koch SSC. Chamberlin AR. J. Org. Chem. 1993, 58: 2725 ; and references therein

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.

Supplementary Material

Supporting Information (PDF) (opens in new window)