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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

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10

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.

12

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.

13

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.

15

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.