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Synlett 2009(11): 1842-1846  
DOI: 10.1055/s-0029-1217361
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Unexpected Formation of Fluorine-Containing Multiply Substituted Dispirocyclohexanes from the Reaction of Ethyl-4,4,4-trifluoro-1,3-dioxobutanoate and 2-Arylideneindane-1,3-diones

Baifan Daia, Liping Song*a,b, Pengyuan Wanga, Hai Yia, Weiguo Caoa, Guifang Jinb, Shizheng Zhu*b, Min Shaoc
a Department of Chemistry, School of Science, Shanghai University, 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 16 February 2009
Publication Date:
12 June 2009 (online)

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Abstract

In the presence of a catalytic amount of piperidine ­(10 mol%), reaction of ethyl 4,4,4-trifluoro-3-oxobutanoate 3 and ­2-arylidene-indane-1,3-diones 4 gave the unexpected fluorine-­containing multiply substituted dispirocyclohexanes 5 in good yields. The structures of compounds 5 were fully confirmed by spectroscopic methods and elemental analysis. A representative compound 5a was further confirmed by XRD analysis. A plausible reaction mechanism for the formation of compounds 5 was presented.

Key words

fluorine-containing - spiro compound - polysubstitution - 2-arylidene-indan-1,3-dione - ethyl 4,4,4-trifluoro-3-oxobutanoate

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A Typical Experimental Procedure for the Preparation of 5a To a mixture of ethyl 4,4,4-trifluoro-3-oxobutanoate (184.0 mg, 1.0 mmol) and 2-benzylidene-indane-1,3-dione (468.0 mg, 2.0 mmol) in MeCN (3.0 mL) was added a catalytic amount of pipreridine (8.5 mg, 0.1 mmol). The resulting mixture was stirred at r.t. until the reaction was completed
(8 h, monitored by TLC). The solvent was removed under reduced pressure. And then the residue was purified by column chromatography on silica gel using PE-EtOAc [6:1 (v/v)] as eluent to afford 5a as a colorless solid in 78% yield.

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Spectroscopic Data for Products 5 Compound 5a: colorless solid (509.0 mg), mp 211-214 ˚C. ¹H NMR (500 MHz, CDCl3): δ = 0.89 (t, J = 7.0 Hz, 3 H, OCH2CH 3), 3.84 (qd, J 1 = 7.0 Hz, J 2 = 3.5 Hz, 2 H, OCH 2CH3), 4.51 (d, J = 12.5 Hz, 1 H, CH), 4.56 (s, 1 H, CH), 5.19 (d, J = 12.5 Hz 1 H, CH), 5.65 (s, 1 H, OH), 6.37 (br, 1 H, ArH), 6.59-7.06 (m, 8 H, ArH), 7.32-7.42 (m, 4 H, ArH), 7.54-7.56 (m, 3 H ArH), 7.66-7.69 (m, 1 H, ArH), 7.93-7.95 (m, 1 H, ArH). ¹9F NMR (470 MHz, CDCl3): δ = -71.63 (s, 3 F, CF3). IR (KBr): 3402, 3062, 2981, 2932, 1745, 1711, 1594, 1247, 1184 cm-¹. ESI-MS: m/z = 653 [M + H]+, 670 [M + NH4]+. Anal. Calcd for C38H27F3O7: C, 69.94; H, 4.17. Found: C, 70.06; H, 4.06.
Compound 5b: colorless solid (510.0 mg), mp 227-229 ˚C. ¹H NMR (500 MHz, CDCl3): δ = 0.91 (t, J = 7.0 Hz, 3 H, OCH2CH 3), 1.78 (s, 3 H, ArCH3), 2.04 (s, 3 H, ArCH3), 3.84 (qd, J 1 = 7.0 Hz, J 2 = 3.5 Hz, 2 H, OCH 2CH3), 4.47 (d, J = 12.5 Hz, 1 H, CH), 4.51 (s, 1 H, CH), 5.15 (d, J = 12.5 Hz, 1 H, CH), 5.63 (s, 1 H, OH), 6.15 (br, 1 H, ArH), 6.50-6.70 (m, 4 H, ArH), 6.82-6.86 (m, 2 H, ArH), 7.24-7.36 (m, 2 H, ArH), 7.39-7.43 (m, 2 H, ArH), 7.66-7.69 (m, 4 H, ArH), 7.92-7.93 (m, 1 H, ArH). ¹9F NMR (470 MHz, CDCl3): δ = -71.65 (s, 3 F, CF3). IR (KBr): 3408, 3029, 2986, 1741, 1712, 1247 cm-¹. ESI-MS: m/z = 681 [M + H]+, 698 [M + NH4]+. Anal. Calcd for C40H31F3O7: C, 70.58; H, 4.59. Found: C, 70.33; H, 4.77.
Compound 5c: colorless solid (617.0 mg), mp 246-247 ˚C. ¹H NMR (500 MHz, CDCl3): δ = 0.96 (t, J = 7.0 Hz, 3 H, OCH2CH 3), 3.89 (qd, J 1 = 7.0 Hz, J 2 = 3.5 Hz, 2 H, OCH 2CH3), 4.69 (d, J = 12.5 Hz, 1 H, CH), 4.71 (s, 1 H, CH), 5.20 (d, J = 12.5 Hz, 1 H, CH), 5.45 (s, 1 H, OH), 6.84-7.28 (m, 4 H, ArH), 7.43-7.53 (m, 3 H, ArH), 7.58-7.71 (m, 5 H, ArH), 7.76-7.80 (m, 2 H, ArH), 7.97-8.00 (m, 2 H, ArH). ¹9F NMR (470 MHz, CDCl3): δ = -71.67 (s, 3 F, CF3). IR (KBr): 3420, 3058, 2979, 2934, 1746, 1710, 1595, 1248, 1188 cm-¹. ESI-MS: 743 [M + H]+, 760 [M + NH4]+. HRMS (MALDI/DHB): m/z calcd for [C38H25F3N2O11 + H]+: 743.1483; found: 743.1501; m/z calcd for [C38H25F3N2O11 + Na]+: 765.1303; found:765.1309.
Compound 5d: colorless solid (584.0 mg), mp 243-244 ˚C. ¹H NMR (500 MHz, CDCl3): δ = 0.95 (t, J = 7.0 Hz, 3 H, OCH2CH 3), 3.87 (qd, J 1 = 7.0 Hz, J 2 = 3.5 Hz, 2 H, OCH 2CH3), 4.49 (d, J = 12.5 Hz, 1 H, CH), 4.53 (s, 1 H, CH), 5.11 (d, J = 12.5 Hz, 1 H, CH), 5.52 (s, 1 H, OH), 6.36-7.07 (m, 7 H, ArH), 7.33-7.51 (m, 4 H, ArH), 7.60-7.72 (m, 3 H, ArH), 7.72-7.75 (m, 1 H, ArH), 7.94-7.96 (m, 1 H, ArH). ¹9F NMR (470 MHz, CDCl3): δ = -71.70 (s, 3 F, CF3). IR (KBr): 3408, 3071, 2986, 2937, 1739, 1713, 1593, 1243, 1196 cm-¹. ESI-MS: m/z = 721, 723, 725 [M + H]+, 738, 740, 742 [M + NH4]+. Anal. Calcd for C38H25Cl2F3O7: C, 63.26; H, 3.49. Found: C, 62.87; H, 3.58.
Compound 5e: colorless solid (551.0 mg), mp 222-223 ˚C. ¹H NMR (500 MHz, CDCl3): δ = 0.92 (t, J = 7.0 Hz, 3 H, OCH2CH 3), 3.86 (qd, J 1 = 7.0 Hz, J 2 = 3.5 Hz, 2 H, OCH 2CH3), 4.49 (d, J = 12.5 Hz, 1 H, CH), 4.54 (s, 1 H, CH), 5.11 (d, J = 12.5 Hz, 1 H, CH ), 5.55 (s, 1 H, OH), 6.09 (br, 1 H, ArH) 6.49-6.93 (m, 6 H, ArH), 7.37-7.49 (m, 4 H, ArH), 7.56-7.60 (m, 3 H, ArH), 7.70-7.73 (m, 1 H, ArH), 7.93-7.95 (m, 1 H, ArH). ¹9F NMR (470 MHz, CDCl3): δ = -71.71 (s, 3 F, CF3), -112.61 (m, 1 F, ArF), -114.13 (m, 1 F, ArF). IR (KBr): 3397, 3087, 2983, 2938, 1743, 1711, 1511, 1247, 1190 cm-¹. ESI-MS: m/z = 689 [M + H]+. Anal. Calcd for C38H25F5O7: C, 66.28; H, 3.66. Found: C, 66.04; H, 3.49.

Compound 5f: colorless solid (620.0 mg), mp 241-243 ˚C. ¹H NMR (500 MHz, CDCl3): δ = 0.94 (br, 3 H, OCH2CH 3), 3.87 (br, 2 H, OCH 2CH3), 4.51 (br, 2 H, CH), 5.13 (br, 1 H, CH), 5.58 (s, 1 H, OH), 6.34-7.01 (m, 7 H, ArH), 7.43-8.00 (m, 9 H, ArH). ¹9F NMR (470 MHz, CDCl3): δ = -71.63 (s, 3 F, CF3). IR (KBr): 3440, 3055, 2984, 1744, 1710, 1593, 1249, 1235, 1176 cm-¹. ESI-MS: m/z = 721, 723, 725 [M + H]+, 738, 740, 742 [M + NH4]+. Anal. Calcd for C38H25Cl2F3O7: C, 63.26; H, 3.49. Found: C, 62.91; H, 3.37.
Compound 5g: colorless solid (743 mg), mp 265-266 ˚C. ¹H NMR (500 MHz, CDCl3): δ = 0.95 (br, 3 H, OCH2CH 3), 3.88 (br, 2 H, OCH 2CH3), 4.48 (br, 2 H, CH), 5.13 (br, 1 H, CH), 5.58 (s, 1 H, OH), 6.61-7.13 (m, 7 H, ArH), 7.35-7.76 (m, 8 H, ArH), 7.95-8.02 (m, 1 H, ArH). ¹9F NMR (470 MHz, CDCl3): δ = -71.61 (s, 3 F, CF3). IR (KBr): 3441, 3072, 2983, 1744, 1711, 1592, 1250, 1178 cm-¹. ESI-MS: m/z = 809, 811, 813 [M + H]+, 826, 828, 830 [M + NH4]+. HRMS (MALDI/DHB): m/z calcd for [C38H25Br2F3O7 + Na]+: 830.9811; found: 830.9817.

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In particular, in the cases of compounds 5f and 5g, the ¹H NMR spectrum showed broad signals due to decreased rotational flexibility of the highly puckered structures.

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CCDC 720376 contains the supplementary crystallographic data for this paper. 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.