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Synlett 2016; 27(13): 1983-1988
DOI: 10.1055/s-0035-1561460
DOI: 10.1055/s-0035-1561460
letter
Enantioselective Michael Addition of Pyrazolin-5-ones to β-CF3-β-Disubstituted Nitroalkenes Catalyzed by Squaramide Organocatalyst
Weitere Informationen
Publikationsverlauf
Received: 28. Februar 2016
Accepted after revision: 25. April 2016
Publikationsdatum:
01. Juni 2016 (online)
![](https://www.thieme-connect.de/media/synlett/201613/lookinside/thumbnails/st-2016-w0139-l_10-1055_s-0035-1561460-1.jpg)
Abstract
A highly enantioselective Michael addition of pyrazolin-5-ones with β-CF3-β-disubstituted nitroalkenes catalyzed by bifunctional squaramide has been developed. Various chiral β-CF3-β-5-hydroxy-pyrazolin-3-yl-disubstituted nitroalkane derivatives bearing all-carbon quaternary stereocenter were prepared in good yields (up to 88%) and excellent enantioselectivities (up to 97% ee).
Key words
Michael addition - pyrazolin-5-ones - β-CF3-β-disubstituted nitroalkenes - squaramide organocatalyst - all-carbon quaternary stereocenterSupporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1561460.
- Supporting Information
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References and Notes
- 1 Malerich JP, Hagihara K, Rawal VH. J. Am. Chem. Soc. 2008; 44: 14416
- 2a Zhu Y, Malerich JP, Rawal VH. Angew. Chem. Int. Ed. 2010; 1: 153
- 2b Konishi H, Lam TY, Malerich JP, Rawal VH. Org. Lett. 2010; 9: 2028
- 2c Işık M, Unver MY, Tanyeli C. J. Org. Chem. 2015; 2: 828
- 2d Bera K, Namboothiri IN. N. J. Org. Chem. 2015; 3: 1402
- 3 For example, see: The Alkaloids: Chemistry and Biology . Vol. 54. Cordell GA. Academic Press; San Diego: 2000. and other volumes in this series
- 4a Lalit K, Chandresh T, Vivek S. Int. J. Res. Pharm. Sci. 2012; 2: 13
- 4b Hamama WS, El-Gohary HG, Kuhnert N, Zoorob HH. Curr. Org. Chem. 2012; 16: 373
- 4c Mariappan G, Sana BP, Sutharson L, Garg S, Pandey L, Kumar DJ. Pharm. Res. 2010; 3: 2856
- 4d Martins MA. P, Freitag R, Flares AF. C, Zanatta N. Synthesis 1995; 1491
- 4e Maser H, Boehner B, Forey W. EP 268554, 1988 ; Chem. Abstr. 1988, 110, 23879
- 4f Li Y, Zhang S, Yang J, Jiang S, Li Q. Dyes Pigm. 2008; 76: 508
- 4g Metwally AA, Khalifa ME, Amer FA. Dyes Pigm. 2008; 76: 379
- 4h Roy A, Nag K. J. Inorg. Nucl. Chem. 1978; 40: 331
- 5a Bondock S, Rabie R, Etman HA, Fadda AA. Eur. J. Med. Chem. 2008; 43: 2122
- 5b Sujatha K, Shanthi G, Selvam NP, Manoharan S, Perumal PT, Rajendran M. Bioorg. Med. Chem. Lett. 2009; 19: 4501
- 5c Brogden RN. Drug 1986; 32: 60
- 6a Kawai H, Nakai H, Suga M, Yuki S, Watanabe T, Saito KI. J. Pharmacol. Exp. Ther. 1997; 281: 921
- 6b Watanabe T, Yuki S, Egawa M, Nishi H. J. Pharmacol. Exp. Ther. 1994; 268: 1597
- 7 Wu TW, Zeng LH, Wu J, Fung KP. Life Sci. 2002; 71: 2249
- 8 Liao Y, Chen W, Wu Z, Du XL, Cun LF, Zhang XM, Yuan WC. Adv. Synth. Catal. 2010; 5: 827
- 9 Li F, Sun L, Teng Y, Yu P, Zhao CG, Ma JA. Chem. Eur. J. 2012; 45: 14255
- 10a Li JH, Du DM. Org. Biomol. Chem. 2013; 36: 6215
- 10b Li JH, Du DM. Org. Biomol. Chem. 2015; 13: 5636
- 11 Wang H, Wang Y, Song H, Zhou ZH, Tang CC. Eur. J. Org. Chem. 2013; 22: 4844
- 12 Hack D, Chauhan P, Deckers K, Mizutani Y, Raabe G, Enders D. Chem. Commun. 2015; 51: 2266
- 13a Corey EJ, Perez AG. Angew. Chem. Int. Ed. 1998; 37: 388
- 13b Douglas CJ, Overman LE. Proc. Natl. Acad. Sci. U.S.A. 2004; 101: 5363
- 13c Christoffers J, Baro A. Adv. Synth. Catal. 2005; 347: 1473
- 13d Trost BM, Jiang C. Synthesis 2006; 369
- 13e Hawner C, Alexakis A. Chem. Commun. 2010; 46: 7295
- 13f Chen J, Meng SX, Wang LM, Tang HM, Huang Y. Chem. Sci. 2015; 6: 4184
- 14a Kirsch P. Modern Fluoroorganic Chemistry: Synthesis Reactivity, Applications. Wiley-VCH; Weinheim: 2013
- 14b Ojima I. Fluorine in Medicinal Chemistry and Chemical Biology. Wiley-Blackwell; Chichester: 2009
- 14c Begue JP, Bonnet-Delpon D. Bioorganic and Medicinal Chemistry of Fluorine . Wiley-VCH; Hoboken: 2008
- 14d Purser S, Moore PR, Swallow S, Gouverneur V. Chem. Soc. Rev. 2008; 37: 320
- 14e Müller K, Faeh C, Diederich F. Science 2007; 317: 1881
- 14f Jeschke P. ChemBioChem 2004; 5: 571
- 14g Isanbor C, Hagan DO. J. Fluorine Chem. 2006; 127: 303
- 14h Hagmann WK. J. Med. Chem. 2008; 51: 4359
- 14i Furuya T, Kamlet AS, Ritter T. Nature (London, U.K.) 2011; 473: 470
- 15a Nie J, Guo HC, Cahard D, Ma JA. Chem. Rev. 2011; 111: 455
- 15b Tomashenko OA, Grushin VV. Chem. Rev. 2011; 111: 4475
- 15c Roy S, Gregg BT, Gribble GW, Le VD. Tetrahedron 2011; 67: 2161
- 15d Qing FL, Zheng F. Synlett 2011; 1052
- 15e Besset T, Schneider C, Cahard D. Angew. Chem. 2012; 124: 5134
- 15f Ye Y, Sanford MS. Synlett 2012; 23: 2005
- 15g Qing FL. Chin. J. Org. Chem. 2012; 32: 815
- 15h Studer A. Angew. Chem. 2012; 124: 9082
- 15i He Z, Huang Y, Verpoort F. Acta Chim. Sin. 2013; 71: 700
- 15j Liang T, Neumann CN, Ritter T. Angew. Chem. 2013; 125: 8372
- 15k Massolo E, Benaglia M, Orlandi M, Rossi S, Celentano G. Chem. Eur. J. 2015; 21: 3589
- 16a Gao JR, Wu H, Xiang B, Yu WB, Han L, Jia YX. J. Am. Chem. Soc. 2013; 8: 2983
- 16b Liu F, Chen J, Feng B, Hu XQ, Ye LH, Lu LQ, Xiao WJ. Org. Biomol. Chem. 2014; 7: 1057
- 16c Chen Q, Wang GQ, Jiang XX, Xu ZQ, Lin L, Wang R. Org. Lett. 2014; 5: 1394
- 17 Vakulya B, Varga S, Csampai A, Soós T. Org. Lett. 2005; 7: 1967
- 18 Wang HX, Wang YM, Song HB, Zhou ZH, Tang CC. Eur. J. Org. Chem. 2013; 4844
- 19 General Procedure for Asymmetric Michael Reactions To a dried small bottle were added (E)-β-F3C-β-disubstituted nitroalkene 1 (0.2 mmol), pyrazolone 2 (0.2 mmol), catalyst VI (0.04 mmol, 20 mol%), and NaOH (0.01 mmol, 5 mol%) in CH2Cl2 (2.0 mL). The mixture was stirred at ice-bath for 24–50 h until TLC showed the reaction was completed, the reaction mixture was concentrated and directly purified by silica gel column chromatography, eluting with EtOAc–PE (1:2, v/v), to afford the corresponding desired product 3. 5-Methyl-2-phenyl-4-(2,2,2-trifluoro-1-nitromethyl-1-phenylethyl)-2H-pyrazol-3-ol (3aa) The title compound 3aa was obtained according to the general procedure as a colorless solid, 73.4 mg (81% yield), mp 188–190 °C. HPLC [Daicel Chiralpak AD-H column (25 cm × 0.46 cm ID), n-hexane–i-PrOH = 90:10, 1.0 mL/min, 254 nm; t R (major) = 12.4 min, t R (minor) = 32.1 min] 97% ee. IR (KBr): ν = 3053, 2615, 1606, 1559, 1500, 1459, 1407, 1374, 1332, 1314, 1298, 1215, 1172, 1148, 1120, 1030, 833, 763, 701 cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 11.87 (s, 1 H), 7.71 (d, J = 7.9 Hz, 2 H), 7.61–7.36 (m, 7 H), 7.27 (t, J = 7.3 Hz, 1 H), 6.26 (d, J = 12.9 Hz, 1 H), 5.78 (d, J = 13.2 Hz, 1 H), 1.47 (s, 3 H) ppm. 13C NMR (126 MHz, DMSO-d 6): δ = 149.09, 136.93, 135.52, 129.47, 129.04, 128.69, 128.49, 127.18 (q, J C–F = 286.0 Hz), 125.92, 120.26, 99.54, 77.68, 53.96 (q, J C–F = 26.5 Hz), 13.13 ppm. 19F NMR (471 MHz, DMSO-d 6): δ = –66.61 (s, 3 F) ppm. ESI-HRMS: m/z calcd for C19H16F3N3NaO3 [M + Na]+: 414.103597; found: 414.103795.
- 20 Synthesis of 4-(3-Amino-1,1,1-trifluoro-2-phenylpropan-2-yl)-3-methyl-1-phenyl-1H-pyrazol-5-ol (4) To a dried small bottle were added 3aa (0.2 mmol) in AcOH (4.0 mL) and excessive zinc powder. The mixture was stirred at room temperature for 6 h until TLC showed the reaction was completed. Then the precipitate was filtered off. The filtrate was adjusted pH to 5–6 with a sat. K2CO3 solution. The organic phase was separated, and the aqueous phase was extracted with CH2Cl2 (2 × 10 mL). The combined organic phase was washed with water (20 mL), then dried (Na2SO4). Removal of the solvent under reduced pressure gave a white crude residue, and the residue was purified with silica gel column chromatography, eluting with EtOAc–PE (1:5, v/v), to afford the desired product 4. Colorless solid, 70.8 mg (98% yield), mp 216–217 °C. HPLC [Daicel Chiralpak AD-H column (25 cm × 0.46 cm ID), n-hexane–i-PrOH = 90:10, 1.0 mL/min, 254 nm; t R (major) = 9.6 min, t R (minor) = 12.2 min] 93% ee. IR (KBr): ν = 3314, 3060, 3033, 2999, 1598, 1498, 1448, 1424, 1352, 1313, 1287, 1274, 1203, 1170, 1140, 1034, 996, 957, 911, 841, 769, 756, 730, 701, 655, 640, 616, 546 cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 9.88 (s, 3 H), 7.99 (d, J = 7.8 Hz, 2 H), 7.48–7.38 (m, 4 H), 7.38–7.29 (m, 3 H), 7.06 (t, J = 7.3 Hz, 1 H), 3.37 (d, J = 13.8 Hz, 1 H), 3.22 (d, J = 13.6 Hz, 1 H), 1.18 (s, 3 H) ppm. 13C NMR (126 MHz, DMSO-d 6): δ = 160.87, 147.31, 141.10, 139.32, 129.06, 128.72, 128.62 (q, J C–F = 286.0 Hz), 127.98, 127.83, 123.44, 119.43, 93.22, 53.49 (q, J C–F = 25.2 Hz), 47.56, 15.42 ppm. 19F NMR (471 MHz, DMSO-d 6): δ = –64.84 (s, 3 F) ppm. ESI-HRMS: m/z calcd for C19H19F3N3O [M + H]+: 362.1480; found: 362.1428.
- 21 Synthesis of 3-Methyl-1-phenyl-4-[1,1,1-trifluoro-3-(4-nitrobenzamido)-2-phenylpropan-2-yl]-1H-pyrazol-5-yl-4-nitrobenzoate (5) To a dried small bottle were added 4 (0.125 mmol) and p-nitrobenzoyl chloride (0.3 mmol) in DMF (2.0 mL). The mixture was stirred at room temperature for 15 min, and Et3N (0.025 mmol) was then added. The mixture was stirred at room temperature for 6 h until TLC showed the reaction was completed. Then water (10 mL) and CH2Cl2 (10 mL) were added. After stirring for 30 min, the organic phase was separated, and the aqueous phase was extracted with CH2Cl2 (2 × 10 mL). The combined organic phase was washed with water (20 mL), then dried (Na2SO4). Removal of the solvent under reduced pressure gave a white crude residue, and the residue was purified with silica gel column chromatography, eluting with EtOAc–PE (1:5, v/v), to afford the desired product 5. Colorless solid, 79.1 mg (96% yield), mp 158–161 °C. HPLC [Daicel Chiralpak AD-H column (25 cm × 0.46 cm ID), n-hexane–i-PrOH = 70:30, 1.0 mL/min, 254 nm; t R (minor) = 15.8 min, t R (major) = 26.5 min] 88% ee. IR (KBr): ν = 3421, 3110, 3074, 2960, 2867, 1767, 1675, 1598, 1530, 1506, 1488, 1441, 1386, 1348, 1320, 1296, 1237, 1215, 1171, 1109, 1059, 1012, 926, 867, 845, 854, 767, 714, 592, 533, 498 cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 8.53 (s, 1 H), 8.38 (d, J = 8.6 Hz, 2 H), 8.31 (d, J = 8.6 Hz, 2 H), 8.19 (s, 2 H), 7.84 (d, J = 8.7 Hz, 2 H), 7.51 (dd, J = 13.5, 7.9 Hz, 4 H), 7.44–7.26 (m, 6 H), 4.58 (dd, J = 13.9, 5.9 Hz, 1 H), 4.50 (dd, J = 14.2, 6.6 Hz, 1 H), 1.79 (s, 3 H) ppm. 13C NMR (126 MHz, DMSO-d 6): δ = 166.20, 161.60, 151.70, 149.46, 148.40, 142.23, 140.75, 137.79, 136.88, 131.99, 131.93, 131.17, 129.91, 129.29, 128.95, 128.91, 128.66, 128.20, 127.20 (q, J C–F = 283.5 Hz) 124.79, 123.00, 105.73, 53.19 (q, J C–F = 23.9 Hz), 42.13, 15.46 ppm. 19F NMR (471 MHz, DMSO-d 6): δ = –66.96 (s, 3 F) ppm. ESI-HRMS: m/z calcd for C33H25F3N5O7 [M + H]+: 660.1700; found: 660.1547.
For reviews of catalytic asymmetric construction of all-carbon quaternary stereocenters, see:
For recent reviews, see: