6728
B. I. Usachev / Tetrahedron Letters 52 (2011) 6726–6728
(15 mL) was added gradually to
a
cooled (ꢁ10 °C) mixture of sodium
The starting CF3-diketones 1 are commercially available or
acetylide suspension 18 wt% slurry in xylene (60 mL) and dry THF (50 mL).
The mixture was stirred at ambient temperature for 2 h, at 70 °C for 30 min,
and at 90 °C for 1.5 h (the low-boiling solvent THF partially distilled off during
heating the reaction mixture in the range 70–90 °C). The mixture was cooled to
ambient temperature and quenched with cold (0 °C) 10% aqueous H2SO4
(200 mL). Hexane (250 mL) was added, and the resulting mixture stirred at 0 °C
for 30 min. The residue was filtered, washed with H2O and hexane, and dried.
The dry residue was dissolved in a minimum volume of a hot mixture of
hexane–toluene (1:1), the hot solution was passed through a layer of silica gel
(5 cm3), and the layer washed with a hot mixture of hexane–toluene (1:1)
(20 mL). The resulting residue was filtered, washed with hexane (5 mL) and
dried to give compound 2a as a white solid. Yield 8.52 g (71%), mp 126–128 °C;
easily obtainable.10
In summary, regioselective nucleophilic addition of the
acetylide anion to 1,3-diketonate anions derived from 1-aryl-
4,4,4-trifluorobutane-1,3-diones has been demonstrated for the
first time. This reaction is of significant interest for the develop-
ment of the chemistry of trifluoromethylated 1,3-diketones
concerning their possible reactions with C-nucleophiles. A novel
double cyclization of 1,8-diaryl-3,6-dihydroxy-3,6-bis(trifluoro-
methyl)oct-4-yne-1,8-diones into 5,50-diaryl-3,30-bis(trifluoro-
methyl)-2,20-bifurans was also discovered.
IR (KBr) 3429, 1698, 1658, 1597 cmꢁ1 1H NMR (400 MHz, CDCl3) d 3.30 (2H, d,
;
J = 17.0 Hz, 2 CHH), 3.63 (2H, d, J = 17.0 Hz, 2 CHH), 5.35 (2H, s, 2 OH), 7.47 (4H,
t, J = 7.3 Hz, 2 Ar–H), 7.63 (2H, t, J = 7.3 Hz, 2 Ar–H), 7.84 (4H, d, 2 Ar–H); 19F
NMR (376.5 MHz, CDCl3, C6F6) d 80.2 (s, CF3); 13C NMR (100 MHz, CDCl3) d 41.3
References and notes
2
(CH2), 70.1 (C-3, C-6, q, JC,F = 32.9 Hz), 81.7 (C-4, C-5), 122.8 (CF3, q,
1JC,F = 283.8 Hz), 128.4 (Ph), 130.0 (Ph), 134.6 (Ph), 136.0 (Ph), 198.1 (CO);
Anal. Calcd for C22H16F6O4: C, 57.65; H, 3.52. Found: C, 57.90; H, 3.45.
6. (a) Vieser, R.; Eberbach, W. Tetrahedron Lett. 1995, 36, 4405–4408; (b) Nicola,
T.; Vieser, R.; Eberbach, W. Eur. J. Org. Chem. 2000, 527–538; (c) Wipf, P.;
Rahman, L. T.; Rector, S. R. J. Org. Chem. 1998, 63, 7132–7133.
1. (a) Garay, E.; Jankowski, P.; Lizano, P.; Marczak, S.; Maehr, H.; Adorini, L.;
Uskokovic, M. R.; Studzinski, G. P. Bioorg. Med. Chem. 2007, 15, 4444–4455; (b)
Maehr, H.; Hong, J. L.; Perry, B.; Suh, N.; Uskokovic, M. R. J. Med. Chem. 2009, 52,
5505–5519; (c) Ohira, Y.; Taguchi, T.; Iseki, K.; Kobayashi, Y. Chem. Pharm. Bull.
1992, 40, 1647–1649; (d) Markwalder, J. A.; Christ, D. D.; Mutlib, A.; Cordova, B.
C.; Klabe, R. M.; Seitz, S. P. Bioorg. Med. Chem. Lett. 2001, 11, 619–622; (e)
Kourist, R.; Bartsch, S.; Bornscheuer, U. T. Adv. Synth. Catal. 2007, 349, 1393–
1398; (f) Ko, S.-J.; Lim, J. Y.; Jeon, N. Y.; Kim, B. T.; Lee, H.; Ha, D.-C.; Won, K.
Tetrahedron: Asymmetry 2009, 20, 1109–1114.
7. Christoffers, J.; Dötz, K. H. Chem. Ber. 1995, 128, 641–644.
8. Werbovetz, K.; Brun, R. Eur. Pat. Appl. EP1726589, 2006; Chem. Abstr. 2006, 146,
27716.
9. 5,5’-Diphenyl-3,3’-bis(trifluoromethyl)-2,2’-bifuran (3a).
Method A. Alkynediol 2a (3.00 g, 6.55 mmol) was added with stirring to a
mixture of Ac2O (20 mL) and CF3SO3H (0.5 mL). The mixture was kept at
ambient temperature for 8 h and then cooled to ꢁ30 °C. The residue was
filtered, washed with cold Ac2O (5 mL) and EtOH (5 mL), and dried to give
compound 3a as cream needles. Yield 2.58 g (93%), mp 168–170 °C; IR (ATR)
2. (a) Nicolaou, K. C.; Krasovskiy, A.; Majumder, U.; Trepanier, V. E.; Chen, D. Y.-K.
J. Am. Chem. Soc. 2009, 131, 3690–3699; (b) Yamazaki, T.; Iwatsubo, H.;
Kitazume, T. Tetrahedron: Asymmetry 1994, 5, 1823–1830; (c) Frey, L. F.; Tillyer,
R. D.; Ouellet, S. G.; Reamer, R. A.; Grabowski, E. J. J.; Reider, P. J. J. Am. Chem.
Soc. 2000, 122, 1215–1216; (d) Hilpert, H.; Wirz, B. Tetrahedron 2001, 57, 681–
694; (e) Shimizu, M.; Fujimoto, T.; Minezaki, H.; Hata, T.; Hiyama, T. J. Am.
Chem. Soc. 2001, 123, 6947–6948; (f) Wu, Y.; Clercq, P. D.; Vandewalle, M.;
Bouillon, R.; Verstuyf, A. Bioorg. Med. Chem. Lett. 2002, 12, 1633–1636; (g) Li, Z.;
Deng, G.; Li, Y.-C. Synlett 2008, 3053–3057; (h) Mello, R.; Alcalde-Aragones, A.;
Gonzalez-Nunez, M. E. Tetrahedron Lett. 2010, 51, 4281–4283; (i) Kawai, H.;
Tachi, K.; Tokunaga, E.; Shibata, N.; Shiro, M. Org. Lett. 2010, 12, 5104–5107; (j)
Konno, T.; Tanikawa, M.; Ishihara, T.; Yamanaka, H. Chem. Lett. 2000, 1360–
1361; (k) Ishizaki, M.; Suzuki, D.; Hoshino, O. J. Fluorine Chem. 2001, 111, 81–
90; (l) Shimizu, M.; Higashi, M.; Takeda, Y.; Jiang, G.; Murai, M.; Hiyama, T.
Synlett 2007, 1163–1165.
1586, 1571, 1516 cmꢁ1 1H NMR (400 MHz, CDCl3) d 6.95 (2H, s, H-4, H-40),
;
7.37 (2H, t, J = 7.4 Hz, 2 Ar–H), 7.45 (4H, t, J = 7.4 Hz, 2 Ar–H), 7.74 (4H, d,
J = 7.4 Hz, 2 Ar–H); 19F NMR (376.5 MHz, CDCl3, C6F6) d 104.0 (s, CF3); 13C NMR
3
(100 MHz, CDCl3) 105.1 (C-4, C-40, q, JC,F = 3.3 Hz), 117.1 (C-3, C-30, q,
2JC,F = 38.9 Hz), 122.0 (CF3, CF03, JC,F = 268.0 Hz), 124.2 (Ph), 128.7 (Ph), 129.01
1
(Ph), 129.04 (Ph), 140.7 (C-2, C-20, qq, 3JC,F = 4.4 Hz, 4JC,F = 1.5 Hz); 154.8 (C-5, C-
50); Anal. Calcd for C22H12F6O2: C, 62.57; H, 2.86. Found: C, 62.53; H, 2.77.
Method B. Alkynediol 2a (0.200 g, 0.44 mmol) was added to dry Et3N (3 mL).
The mixture was cooled to 0 °C, and (CF3CO)2O (1.0 mL) was added gradually
over 2 min. The mixture was stirred at 0 °C for 20 min and at ambient
temperature for 20 min. Then the mixture was carefully diluted with AcOH
(3 mL) and H2O (1 mL). The residue was filtered, washed with EtOH, and
3. (a) Tarrant, P.; Warner, D. A.; Taylor, R. E. J. Am. Chem. Soc. 1953, 75, 4360–
4362; (b) Fleck, B.; Kmiecik, J. J. Org. Chem. 1957, 22, 90–92.
4. (a) Papa, D.; Villani, F. J.; Ginsberg, H. F. J. Am. Chem. Soc. 1954, 76, 4446–4450;
(b) Davis, R. B.; Hurd, P. J. Am. Chem. Soc. 1955, 77, 3284–3287.
crystallized from
a mixture of EtOH and isoamyl alcohol (1:1) to give
compound 3a as cream needles. Yield 0.135 g (73%), mp 168–170 °C.
10. (a) Reid, J. C.; Calvin, M. J. Am. Chem. Soc. 1950, 72, 1952–2948; (b) Barkley, L.
B.; Levine, R. J. Am. Chem. Soc. 1951, 73, 1627–4625.
5. 3,6-Bis(trifluoromethyl)-3,6-dihydroxy-1,8-diphenyloct-4-yne-1,8-dione (2a): The
reaction was conducted under an argon atmosphere.
A solution of 4,4,4-
trifluoro-1-phenylbutane-1,3-dione (1a) (11.3 g, 52.3 mmol) in dry THF