PDF herunterladen
Synlett 2009(7): 1131-1135  
DOI: 10.1055/s-0028-1088155
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Preparation and Reactivity of some New Keto- and Styrene-Based Trifluoromethoxylated Synthons

Riadh Zriba, Emmanuel Magnier*, Jean-Claude Blazejewski
Institut Lavoisier de Versailles (ILV), UMR CNRS 8180, Université de Versailles, St Quentin en Yvelines, 45 Avenue des Etats-Unis, 78035 Versailles Cedex, France
Fax: +33(1)39254452; e-Mail: magnier@chimie.uvsq.fr;
Weitere Informationen

Publikationsverlauf

Received 19 January 2009
Publikationsdatum:
20. März 2009 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik

Abstract

We describe the preparation, by the means of an initial fluorodesulfurization reaction, of 2-trifluoromethoxy acetophenone as well as β-trifluoromethoxystyrenes derivatives. The synthesis and reactivity of these compounds are discussed in relation to the perturbation induced by the aliphatic trifluoromethoxy group.

Key words

ethers - fluorine - halogenation - Heck reaction - ketones

    References and Notes

  • 1 Olah GA. Yamato T. Hashimoto T. Shih JG. Trivedi N. Singh BP. Piteau M. Olah JA. J. Am. Chem. Soc.  1987,  109:  3708 
    CrossrefGoogle Scholar
  • 2 Leroux F. Jeschke P. Schlosser M. Chem. Rev.  2005,  105:  827 
    CrossrefPubMedGoogle Scholar
  • 3 However, see: Iijima A. Amii H. Tetrahedron Lett.  2008,  49:  6013 
    CrossrefGoogle Scholar
  • 4a Aldrich PE. Sheppard WA. J. Org. Chem.  1964,  29:  11 
    Google Scholar
  • 4b Yagupol’skii LM. Alekseenko AN. Il’chenko AY. Sov. Prog. Chem. (Engl. Transl.)  1978,  44:  52 
    Google Scholar
  • 5a Barton DHR. Danks LJ. Ganguly AK. Hesse RH. Tarzia G. Pechet MM. J. Chem. Soc., Perkin Trans. 1  1976,  101 
    Google Scholar
  • 5b Barton DHR. Hesse RH. Jackman GP. Pechet MM. J. Chem. Soc., Perkin Trans. 1  1977,  2604 
    Google Scholar
  • 5c Kamil WA. Haspel-Hentrich F. Shreeve JM. Inorg. Chem.  1986,  25:  376 ; and references cited therein
    Google Scholar
  • 5d Leroy J. Wakselman C. J. Chem. Soc., Perkin Trans. 1  1978,  1224 
    Google Scholar
  • 6a Kollonitsch J. Marburg S. Perkins LM. J. Org. Chem.  1976,  41:  3107 
    Google Scholar
  • 6b Sondej SC. Katzenellenbogen JA. J. Org. Chem.  1986,  51:  3508 
    Google Scholar
  • 7a Kuroboshi M. Kanie K. Hiyama T. Adv. Synth. Catal.  2001,  343:  235 
    Google Scholar
  • 7b Shimizu M. Hiyama T. Angew. Chem. Int. Ed.  2005,  44:  214 
    Google Scholar
  • 8 Kanie K. Tanaka Y. Suzuki K. Kuroboshi M. Hiyama T. Bull. Chem. Soc. Jpn.  2000,  73:  471 
    CrossrefGoogle Scholar
  • 9a Kirsch P, Franz K.-D, and Ruhl A. inventors; WO  2006072401. 
  • 9b Kirsch P, Franz K.-D, and Ruhl A. inventors; US  2008149878. 
  • 9c Wolfgang H, Ignatyev NM, Seidel M, Montenegro E, Kirsch P, and Bathe A. inventors; WO  2008003444. 
  • 9d Wolfgang H, Ignatyev NM, Seidel M, Montenegro E, Kirsch P, and Bathe A. inventors; WO  2008003446. 
  • 9e

    We thank one of the referees for bringing these works to our attention.

  • 10 Blazejewski J.-C. Anselmi E. Wakselman C. J. Org. Chem.  2001,  66:  1061 
    CrossrefGoogle Scholar
  • 11 Blazejewski J.-C. Anselmi E. Wernicke A. Wakselman C. J. Fluorine Chem.  2002,  117:  161 
    CrossrefGoogle Scholar
  • 12 Umemoto T. Adachi K. Ishihara S. J. Org. Chem.  2007,  72:  6905 
    CrossrefGoogle Scholar
  • 13 Christe KO. Hegge J. Hoge B. Haiges R. Angew. Chem. Int. Ed.  2007,  46:  6155 
    CrossrefGoogle Scholar
  • 14 Kolomeitsev AA. Vorobyev M. Gillandt H. Tetrahedron Lett.  2008,  49:  449 
    CrossrefGoogle Scholar
  • 16 Anselmi E. Blazejewski J.-C. Wakselman C. Tetrahedron Lett.  1998,  39:  9651 
    CrossrefGoogle Scholar
  • 17 Lee AWM. Chan WH. Wong HC. Wong MS. Synth. Commun.  1989,  19:  547 
    CrossrefGoogle Scholar
  • 19 Hudlicky M. Oxidations in Organic Chemistry   ACS Monograph 186:  American Chemical Society; Washington DC: 1990. 
    Google Scholar
  • 20 Trömel M. Russ M. Angew. Chem., Int. Ed. Engl.  1987,  26:  1007 
    CrossrefGoogle Scholar
  • 22 Agouridas V. Laïos I. Cleeren A. Kizilian E. Magnier E. Blazejewski J.-C. Leclercq G. Bioorg. Med. Chem.  2006,  14:  7531 
    CrossrefGoogle Scholar
  • 23 March J. In Advanced Organic Chemistry: Reactions, Mechanisms, and Structure   4th ed.:  John Wiley and Sons; New York: 1992.  p.694-697  
    Google Scholar
  • 25 Farnham WB, and Middleton WJ. inventors; EP 164124 A2  19851211.  ; Chem. Abstr. 1985, 105, 114600
  • 26 This compound was also obtained albeit in poor yield (10%) upon oxidation with NaBrO3/NaHSO3 system. See: Kikuchi D. Sakaguchi S. Ishii Y. J. Org. Chem.  1998,  63:  6023 
    CrossrefGoogle Scholar
  • 27 Smith JG. Dribble PW. Sandborn RE. J. Org. Chem.  1986,  51:  3762 
    CrossrefGoogle Scholar
  • 28 Gelling JO. Feringa BL. J. Am. Chem. Soc.  1990,  12:  7599 
    Google Scholar
  • 30 Poirier J.-M. Hennequin L. Fomani M. Bull. Soc. Chim. Fr.  1986,  436 
    Google Scholar
  • 32 Pravst I. Zupan M. Stavber S. Tetrahedron  2008,  64:  5191 
    CrossrefGoogle Scholar
  • 34 Magnier E. Diter P. Blazejewski J.-C. Tetrahedron Lett.  2008,  49:  4575 
    CrossrefGoogle Scholar
  • 35a Ernet T. Haufe G. Tetrahedron Lett.  1996,  37:  7251 
    Google Scholar
  • 35b Bogachev AA. Kobrina LS. Meyer OGJ. Haufe G. J. Fluorine Chem.  1999,  97:  135 
    Google Scholar
  • 36 Miyaura N. Suzuki A. Chem. Rev.  1995,  95:  2457 
    Google Scholar
15

The preparation of some α-trifluoromethoxylated esters was recently described using the direct nucleophilic substitution of α-triflyl esters with the trifluoromethoxide anion, see ref. 14. However, the possibility to extend this reaction to the case of α-keto triflates remains to be established.

18

Preparation of Phenethyl Trifluoromethyl Ether (3a)
HF-pyridine complex (50 mL) was added dropwise to a cooled (-78 ˚C) suspension of 1,3-dibromo-5,5-dimethyl-hydantoin (DBH, 55 g, 1.92 mol) in CH2Cl2 (250 mL), followed by a solution of the xanthate (15 g, 70.7 mmol) in CH2Cl2 (40 mL). The mixture was stirred at -78 ˚C for 1 h, then for 2 h at r.t., and poured in cold H2O (200 mL). The organic layer was separated. The aqueous phase was sat. with NaCl and extracted with CH2Cl2 (2 × 100 mL). The combined organic layers were washed with a 37% NaHSO3 solution, brine (2 × 250 mL), dried over MgSO4, and concentrated under vacuum. The residue was purified by flash chromatography (SiO2, pentane) to give 9.5 g of a mixture of brominated and nonbrominated products. This mixture was dissolved in dry THF (56 mL), cooled at -78 ˚C under argon, and a solution of n-BuLi in hexanes (2.5 M, 11.3 mL) was added dropwise. The solution was stirred for an additional 30 min, H2O (10 mL) was added, and the mixture was warmed to r.t. A sat. soln of NH4Cl (50 mL) and Et2O (50 mL) were added and the two phases separated. The aqueous layer was extracted twice with Et2O (50 mL). The organic layers were combined, washed with brine (100 mL), dried (MgSO4), and concentrated under vacuum to give 7.6 g (58%) of pure 3a as a colorless oil. The spectroscopic data were in full accord with previous publication.¹² ¹H NMR (200 MHz, CDCl3): δ = 3.01 (t, J = 7.3 Hz, 2 H, CH2), 4.16 (t, J = 7.3 Hz, 2 H, CH2), 7.18-7.41 (m, 5 H, 5CHAr). ¹³C NMR (50 MHz, CDCl3): δ = 35.3 (CH2), 67.8 (q, J CF = 3 Hz, CH2), 121.4 (q, J CF = 254 Hz, C), 127.0 (CHAr), 128.7 (2 CHAr), 129.0 (2 CHAr), 136.6 (CAr). ¹9F NMR (188 MHz, CFCl3): δ = -61.2 (OCF3). MS: m/z (%) = 191 [M + H+], 105 (100) [C8H9 +].

21

Leroux, F. R.; Manteau, B.; Vors, J.-P.; Pazenok, S. Beilstein J. Org. Chem. 2008, 4, doi:10.3762/bjoc.4.13.

24

Preparation of (2,2-Dibromo-2-phenyl)ethyl Trifluoromethyl Ether (4b)
A solution of trifluoromethyl ether 3a (5 g, 26.3 mmol), NBS (14.04 g, 78.9 mmol), and AIBN (0.21 g, 1.3 mmol) in CCl4 (100 mL) was refluxed until completion (TLC). The mixture was concentrated, and the residue was filtered through a short silica gel column, rinsed with pentane. After concentration of the filtrate, the resulting oil was purified by flash chromatography (SiO2, pentane) to give 9 g (99%) of 4b as a yellow oil. ¹H NMR (200 MHz, CDCl3): δ = 4.70 (s, 2 H, CH2), 7.31 (3 H, CHAr), 7.69 (m, 2 H, CHAr). ¹³C NMR (50 MHz, CDCl3): δ = 61.9 (C), 75.3 (q, J CF = 3 Hz, CH2), 121.1 (q, J CF = 257 Hz, C), 127.3 (2 CHAr), 128.6 (2 CHAr), 129.9 (CHAr), 140.5 (C). ¹9F NMR (188 MHz, CFCl3): δ = -60.8 (OCF3). Anal. Calcd (%) for C9H7Br2F3O: C, 31.07; H, 2.02. Found: C, 31.12; H, 1.76.

29

2-Trifluoromethoxy Acetophenone (6)
Compound 4b (9.1 g) was refluxed for 8 h in a solution of 10% HCl (150 mL) and MeCN (60 mL). After extraction with Et2O (4 × 50 mL), the organic layers were dried (MgSO4) and concentrated under reduced pressure. Flash chromatography (SiO2, pentane-Et2O, 9:1) afforded 4.48 g (84%) of 6 as a colorless oil. ¹H NMR (200 MHz, CDCl3): δ = 5.17 (s, 2 H, CH2), 7.48 (m, 2 H, CHAr), 7.62 (m, 1 H, CHAr), 7.88 (m, 2 H, CHAr). ¹³C NMR (50 MHz, CDCl3): δ = 68.3 (q, J CF = 2.7 Hz, CH2), 121.7 (q, J CF = 254 Hz, CF3), 126.8 (2 CHAr), 129.0 (2 CHAr), 133.7 (CAr), 134.3 (CHAr), 190.2 (C). ¹9F NMR (188 MHz, CFCl3): δ = -61.5. Anal. Calcd (%) for C9H7F3O2: C, 52.95; H, 3.46. Found: C, 52.71; H, 3.29. MS: m/z (%) = 205 (100) [M + H+].

31

1- tert -Butyldimethylsilyloxy-2-trifluoromethoxystyrene (9)
To a solution of ketone 6 (0.31 g, 1.52 mmol) in THF (10 mL) was added, at -78 ˚C under argon, KHMDS (3.8 mL, 2.43 mmol, 1.0 M solution in toluene) and HMPA (0.3 mL, 1.52 mmol). After 5 min, a solution of TBSCl (340 mg, 2.28 mmol) in THF (2 mL) was added dropwise and stirring was continued at the same temperature for 8 h. The reaction mixture was allowed to reach r.t. and a sat. soln of NH4Cl was added. The organic layer was collected, washed with brine, dried (MgSO4), and concentrated. The product was purified by flash chromatography (SiO2, pentane-Et2O, 9:1) to give 0.53 g (99%) of 9 as a colorless oil. ¹H NMR (200 MHz, CDCl3): δ = 0.12 (s, 6 H, 2 CH3), 0.98 (s, 9 H, 3 CH3), 6.48 (s, 1 H, CH), 7.35-7.45 (m, 3 H, 3CHAr), 7.46-7.52 (m, 2 H, 2 CHAr). ¹³C NMR (50 MHz, CDCl3): δ = -4.34 (s, 2 CH3), 18.57 (C), 25.79 (3 CH3), 119.40 (q, J C-F = 13.0 Hz, CH), 120.9 (q, J C-F = 257 Hz, CF3), 125.6 (2 CHAr), 128.5 (2 CHAr), 128.8 (CHAr), 135.2 (CAr), 142.5 (C). ¹9F NMR (188 MHz, CFCl3): δ = -60.9. Anal. Calcd (%) for C15H21F3O2Si: C, 56.58; H, 6.65. Found: C, 56.65; H, 6.96.

33

α-Bromo-β-trifluoromethoxystyrene (10b)
DBU (1.66 mL, 11.1 mmol) was added to a solution of dibromide 4b (2.95 g, 8.52 mmol) in dry Et2O (60 mL). The mixture was refluxed for 8 h. After evaporation of the solvent, the crude product was purified by flash chromatography (SiO2, pentane) giving 2.1 g (92%) of a mixture of Z/E isomers of 10b as a colorless oil. Anal. Calcd (%) for C9H6BrF3O: C, 40.48; H, 2.26. Found: C, 40.49; H, 2.41. Further purification allowed the separation of the two isomers.
E-Isomer: ¹H NMR (200 MHz, CDCl3): δ = 7.10 (s, 1 H, CH), 7.35 (m, 3 H, CHAr), 7.46 (m, 2 H, CHAr). ¹³C NMR (50 MHz, CDCl3): δ = 112.9 (C), 121.1 (q, J CF = 258 Hz, CF3), 127.9 (2 CHar), 128.8 (2 CHAr), 129.6 (CHAr), 132.9 (q, J CF = 3 Hz, CH), 134.9 (CAr). ¹9F NMR (188 MHz, CFCl3): δ = -60.4 (OCF3).
Z-Isomer: ¹H NMR (200 MHz, CDCl3): δ = 6.95 (s, 1 H, CH), 7.37 (m, 3 H, CHAr), 7.55 (m, 2 H, CHAr). ¹9F NMR (188 MHz, CFCl3): δ = -60.9 (OCF3).

37

Preparation of α-(3,5-Dimethylphenyl)-β-trifluoromethoxystyrene (11)
A mixture of bromostyrene 10b (212 mg, 0.8 mmol), Pd(PPh3)4 (44 mg, 0.5 mol%), 3,5-dimethylbenzene boronic acid (144 mg, 0.96 mmol), Cs2CO3 (520 mg, 1.6 mmol), distilled H2O (0.32 mL), and toluene (8 mL) was stirred for 2 h at reflux. The solution was extracted with Et2O (4 × 10 mL). Drying of the organic layers (MgSO4), followed by concentration and flash chromatography (SiO2, pentane) gave 199 mg (85%) of pure 11 as a colorless oil. ¹H NMR (200 MHz, CDCl3): δ = 2.20 (s, 6 H, 2 CH3), 6.66 (s, 1 H, CH), 6.82 (s, 2 H, 2 CHar), 6.87 (s, 1 H, CHAr), 7.15 (m, 2 H, CHAr), 7.21 (m, 3 H, CHAr). ¹³C NMR (50 MHz, CDCl3): δ = 21.3 (2 CH3), 121.6 (q, J CF = 256 Hz, C), 127.7 (2 CHar), 128.1 (CHAr), 128.3 (2 CHAr), 128.6 (2 CHAr), 129.8 (CHAr), 130.7 (C), 130.8 (q, J CF = 3.8 Hz, CH), 135.3 (C), 137.8 (C), 138.3 (C). ¹9F NMR (188 MHz, CFCl3): δ = -60.63. Anal. Calcd (%) for C17H15F3O: C, 69.85; H, 5.17. Found: C, 70.09; H, 5.27.