Synlett 2009(4): 589-594  
DOI: 10.1055/s-0028-1087924
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Micellar-System-Mediated Direct Fluorination of Ketones in Water

Gaj Stavbera, Marko Zupana, Stojan Stavber*b
a Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, 1000 Ljubljana, Slovenia
b Laboratory of Organic and Bioorganic Chemistry, Jo˛ef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia
Fax: +386(1)423-5400; e-Mail: stojan.stavber@ijs.si;
Further Information

Publication History

Received 12 November 2008
Publication Date:
16 February 2009 (online)

Abstract

A micellar system was developed and applied for direct regioselective fluorination of a variety of cyclic and acyclic ketones to α-fluoroketones in water as reaction medium with Selectfluor F-TEDA-BF4 as fluorinating reagent. The inexpensive ionic amphiphile sodium dodecyl sulfate (SDS) was found to be an excellent promoter for fluorofunctionalization of hydrophobic ketones without prior activation or use of acid catalysts.

    References and Notes

  • 1a Hudlicky M. Pavlath AE. Chemistry of Organic Fluorine Compounds II. A Critical Review   ACS Monograph 187:  American Chemical Society; Washington DC: 1995. 
  • 1b Kirk KL. J. Fluorine Chem.  2006,  127:  1013 ; and references cited therein
  • 1c Hagmann WK.
    J. Med. Chem.  2008,  51:  4359 ; and references cited therein
  • 2a Wakefield B. Innovat. Pharmaceut. Technol.  2000,  74 ; http://www.iptonline.com/articles/public/IPTFOUR74NP.pdf
  • 2b Müller K. Faeh C. Diederich F. Science  2007,  317:  1881 
  • 3 Borodin A. Justus Liebigs Ann. Chem.  1863,  126:  58 
  • 4a Lal GS. Pez GP. Syvret RG. Chem. Rev.  1996,  96:  1737 
  • 4b Furin GG. Fainzilberg AA. Russ. Chem. Rev.  1999,  68:  653 
  • 4c Modern Organofluorine Chemistry - Synthetic Aspects, In Advances in Organic Synthesis   Vol. 2:  Lalli KK. . Bentham Science; Amsterdam: 2006. 
  • 5a Stavber S. Zupan M. Modern Organofluorine Chemistry - Synthetic Aspects, In Advances in Organic Synthesis   Vol. 2:  Lalli KK. . Bentham Science; Amsterdam: 2006.  p.213-268  ; and references cited therein
  • 5b Singh PR. Shreeve MJ. Acc. Chem. Res.  2004,  37:  31 
  • 5c Nyffeler PT. Duron SG. Burkart MD. Vincent SP. Wong C.-H. Angew. Chem. Int. Ed.  2004,  44:  192 
  • 6a Lancaster M. Green Chemistry   RSC; Cambridge: 2002. 
  • 6b Anastas PT. Warner JC. Green Chemistry: Theory and Practice   Oxford University Press; New York: 1998. 
  • 6c Sheldon RA. Green Chem.  2005,  7:  267 
  • 6d Clark JH. Tavener S. Org. Process Res. Dev.  2007,  11:  149 ; and references cited therein
  • 7a Organic Reactions in Water: Principles, Strategies and Applications   Lindström UM. Blackwell; Oxford: 2007. 
  • 7b Herrerias CI. Yao X. Li Z. Li C.-J. Chem. Rev.  2007,  107:  2546 
  • 7c Dallinger D. Kappe CO. Chem. Rev.  2007,  107:  2563 
  • 8a Narayan S. Muldoon J. Finn MG. Fokin VV. Kolb CH. Sharpless KB. Angew. Chem. Int. Ed.  2005,  44:  3275 
  • 8b Hayashi Y. Angew. Chem. Int. Ed.  2006,  45:  8103 
  • 8c Klijn JE. Engberts JBFN. Nature (London)  2005,  435:  746 
  • 9a Engberts JBFN. In Organic Reactions in Water: Principles, Strategies and Applications   Lindström UM. Blackwell; Oxford: 2007.  p.47-55  ; and references cited therein
  • 9b Sijbren O. Engberts JBFN. Org. Biomol. Chem.  2003,  1:  2809 ; and references cited therein
  • 10a Breslow R. Acc. Chem. Res.  1991,  24:  159 
  • 10b Lindström UM. Andersson F. Angew. Chem. Int. Ed.  2006,  45:  548 
  • 11a Breslow R. Acc. Chem. Res.  2004,  37:  471 
  • 11b Luche JL. Synthetic Organic Sonochemistry   Plenum Press; New York: 1998. 
  • 11c Tascioglu S. Tetrahedron  1996,  52:  11113 
  • 11d Kobayashi S. Manabe K. Acc. Chem. Res.  2002,  35:  209 
  • 12a Dwars T. Paetzold E. Oehme G. Angew. Chem. Int. Ed.  2005,  44:  7174 ; and references cited therein
  • 12b Ogawa C. Kobayashi S. In Organic Reactions in Water: Principles, Strategies and Applications   Lindström UM. Blackwell; Oxford: 2007.  p.79-91  
  • 12c Bunton CA. Nome F. Quina FH. Romsted LS. Acc. Chem. Res.  1991,  24:  359 
  • 13a Jereb M. Zupan M. Stavber S. Green. Chem.  2004,  7:  100 
  • 13b Pavlinac J. Zupan M. Stavber S. J. Org. Chem.  2006,  71:  1027 
  • 13c Kralj P. Zupan M. Stavber S. J. Org. Chem.  2006,  71:  3880 
  • 13d Pavlinac J. Zupan M. Stavber S. Synthesis  2006,  2603 
  • 13e Pravst I. Zupan M. Stavber S. Tetrahedron Lett.  2006,  47:  4707 
  • 13f Podgoršek A. Stavber S. Zupan M. Iskra J. Green Chem.  2007,  9:  1212 
  • 14 Taylor SD. Kotoris CC. Hum G. Tetrahedron  1999,  55:  12431 
  • 15a Stavber S. Zupan M. Tetrahedron Lett.  1996,  37:  3591 
  • 15b Stavber S. Jereb M. Zupan M. Chem. Commun.  2000,  1323 
  • 15c Stavber S. Jereb M. Zupan M. Synthesis  2002,  2609 
  • 15d Stavber G. Zupan M. Jereb M. Stavber S. Org. Lett.  2004,  6:  4973 
  • 16a Duplatre G. Ferreira-Marques MF. da Graça-Miguel M. J. Phys. Chem.  1996,  100:  16608 
  • 16b Wang T.-Z. Mao S.-Z. Miao X.-J. Zhao S. Yu J.-Y. Du Y.-R. J. Colloid Interface Sci.  2001,  241:  465 
  • 16c Cui X. Mao S. Liu M. Yuan H. Du Y. Langmuir  2008,  24:  10771 
  • 17a Syvret RG. Kathleen MB. Nguyen TP. Bulleck VL. Rieth RD. J. Org. Chem.  2002,  67:  4487 
  • 17b Ye C. Shreeve JM. J. Org. Chem.  2004,  69:  8561 
  • 18 Keeffe JR. Kresge AJ. Schepp NP. J. Am. Chem. Soc.  1990,  112:  4862 
  • 20 Thomas MG. Suckling CJ. Pitt AR. Suckling KE. J. Chem. Soc., Perkin Trans. 1  1999,  3191 
  • 21 The graphical abstract drawing was inspired by that of the article: Manabe K. Iimura S. Sun X.-M. Kobayashi S. J. Am. Chem. Soc.  2002,  124:  11971 
  • 22 Stavber S. Zupan M. J. Org. Chem.  1987,  52:  5022 
  • 23 Resnati G. DesMarteau DD. J. Org. Chem.  1991,  56:  4925 
  • 24 Welch JT. Seper KW. J. Org. Chem.  1988,  53:  2991 
19

General Procedure for the Direct Fluorination of Ketones in SDS Aqueous Micellar System
Ketone (1 mmol) was placed in a glass flask (25 mL) equipped with a magnetic stirrer. Then, H2O (5 mL) was added and stirred for a few minutes. An appropriate amount of SDS (144 mg, 0.5 mmol or 288 mg, 1 mmol; see Table  [³] ) was then added to the heterogeneous reaction system and heated to 80 ˚C during rapid stirring. When the reaction system reached 80 ˚C, F-TEDA-BF4 (390 mg, 1.1 mmol) was added in two portions over an interval of 1 h, and stirred and held at 80 ˚C until the KI test showed consumption of the fluorinating reagent. When reaction was complete, the reaction system was cooled to r.t., and the resulting suspension was extracted with Et2O (2 × 15 mL). The combined ether phases were dried over anhyd Na2SO4. After the removal of the solvent under reduced pressure, the crude products obtained were identified with ¹H NMR, ¹9F NMR, and MS analysis and purified by silica gel column chromatography or preparative TLC (SiO2, CH2Cl2, and a few drops of EtOH) to afford pure α-fluoro ketones. The spectroscopic data of the products were in agreement with those reported in the literature.
Spectroscopic Data for Representative Compounds
1-Fluoro-1-phenylpropan-2-one ²² (21)
Liquid product. ¹H NMR (300 MHz, CDCl3): δ = 2.23 (d, J = 4.0 Hz, 3 H, Me), 5.68 (d, J = 48.7 Hz, 1 H, CHF), 7.40 (br s, 5 H, ArH). ¹9F NMR (285 MHz, CDCl3): δ = -183.14 (dq, J = 48.7, 4.0 Hz). ¹³C NMR (76.2 MHz, CDCl3): δ = 25.13 (Me), 95.84 (d, J = 187.8 Hz, C-1), 126.00 (d, J = 7.0 Hz), 128.9, 129.36 (d, J = 2.3 Hz), 133.94 (d, J = 20.6 Hz), 204.55 (d, J = 26.7 Hz, CO). MS (EI, 70eV):
m/z (%) = 152 (6) [M+], 110 (10), 109 (100), 83 (20).
1-Fluoro-1,1-diphenyl-propan-2-one ²³ (23)
Mp 58.5-60.0 ˚C. ¹H NMR (300 MHz, CDCl3): δ = 2.41 (d, J = 5.9 Hz, 3 H, Me), 7.37 (br s, 10 H, ArH). ¹9F NMR (285 MHz, CDCl3): δ = -143.62 (q, J = 5.9 Hz). ¹³C NMR (76.2 MHz, CDCl3): δ = 26.71 (Me), 102.17 (d, J = 185.8 Hz,
C-1), 126.64 (d, J = 7.4 Hz), 128.34, 128.77 (d, J = 2.0 Hz), 137.54 (d, J = 22.8 Hz), 206.43 (d, J = 32.7 Hz, CO).
MS (EI, 70eV): m/z (%) = 185 (100) [M+ - COMe], 151 (11).
3-Fluoro-4-phenylbutan-2-one ²4 (27)
Liquid product. ¹H NMR (300 MHz, CDCl3): δ = 2.13 (d, J = 4.9 Hz, 3 H, Me), 3.01-3.21 (m, 2 H, CH2), 4.93 (ddd, J = 48.5, 6.0, 3.0 Hz, 1 H, CHF), 7.21-7.34 (m, 5 H, ArH). ¹9F NMR (285 MHz, CDCl3): δ = -188.66 (dtq, J = 48.5, 23.2, 5.0 Hz). ¹³C NMR (76.2 MHz, CDCl3): δ = 26.42 (Me), 38.10 (d, J = 20.6 Hz, C-4), 95.89 (d, J = 187.3 Hz,
C-3), 127.10, 128.57, 129.49, 135.28, 209.98 (d, J = 26.7 Hz, CO). MS (EI, 70eV): m/z (%) = 166 (100) [M+], 146 (100), 123 (15), 91 (77), 77 (41).