Download PDF
Synthesis 2005(1): 39-46  
DOI: 10.1055/s-2004-834910
PAPER
© Georg Thieme Verlag Stuttgart · New York

Friedel-Crafts Cyclization of 1,1-Difluoroalk-1-enes: Synthesis of Benzene-Fused Cyclic Ketones via α-Fluorocarbocations

Junji Ichikawa*a, Hideharu Jyonob, Takao Kudob, Masaki Fujiwaraa, Misaki Yokotaa
a Department of Chemistry, Graduate School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Fax: +81(3)58414345; e-Mail: junji@chem.s.u-tokyo.ac.jp;
b Department of Applied Chemistry, Kyushu Institute of Technology, Sensui-cho, Tobata, Kitakyushu 804-8550, Japan
Further Information

Publication History

Received 10 August 2004
Publication Date:
17 November 2004 (online)

    Permissions and Reprints All articles of this category

Abstract

1,1-Difluoroalk-1-enes bearing a phenyl group at the C-3, -4, or -5 position, readily obtained from 2,2,2-trifluoroethyl p-toluenesulfonate, are treated with FSO3H·SbF5 to undergo Friedel-Crafts cyclization in (CF3)2CHOH. The cyclization takes place via α-fluorocarbocations, followed by spontaneous hydrolysis of the C-F bond to afford bicyclic ketones including a five, six, or seven-membered ring in good yield.

Key words

Friedel-Crafts cyclization - difluoroalkene - bicyclic ketone - α-fluorocarbocation - fluoroalcohol solvent

    References

  • 1 Smart BE. In Organofluorine Chemistry, Principles and Commercial Applications   Banks RE. Smart BE. Tatlow JC. Plenum Press; New York: 1994. 
    Google Scholar
  • 2a Tian F. Battiste MA. Dolbier WR. Org. Lett.  1999,  1:  193 
    CrossrefGoogle Scholar
  • 2b McAllister M. Tidwell TT. Peterson MR. Csizmadia IG. J. Org. Chem.  1991,  56:  575 
    CrossrefGoogle Scholar
  • 2c Kispert LD. Pittman CU. Allison DL. Patterson TB. Gilbert CW. Hains CF. Prather J. J. Am. Chem. Soc.  1972,  94:  5979 
    CrossrefGoogle Scholar
  • 2d For a review on fluorinated carbocations, see: Allen AD. Tidwell TT. Advances in Carbocation Chemistry   Vol. 1:  Jai Press; Grennwich Conn.: 1989.  p.1 
    CrossrefGoogle Scholar
  • For reports where the effect of fluorine on carbocations was advantageously applied in organic synthesis, see:
  • 3a Johnson WS. Daub GW. Lyle TA. Niwa M. J. Am. Chem. Soc.  1980,  102:  7800 
    CrossrefGoogle Scholar
  • 3b Johnson WS. Lyle TA. Daub GW. J. Org. Chem.  1982,  47:  161 
    CrossrefGoogle Scholar
  • 3c Fish PV. Johnson WS. Jones GS. Tham FS. Kullnig RK. J. Org. Chem.  1994,  59:  6150 ; and references cited therein
    CrossrefGoogle Scholar
  • 3d Morikawa T. Kumadaki I. Shiro M. Chem. Pharm. Bull.  1985,  33:  5144 
    CrossrefGoogle Scholar
  • For recent reports on the allylic rearrangement of fluoroallylalcohol derivatives, see:
  • 4a Funabiki K. Sawa K. Shibata K. Matsui M. Synlett  2002,  1134 
    CrossrefGoogle Scholar
  • 4b Ichikawa J. Fujiwara M. Miyazaki S. Ikemoto M. Okauchi T. Minami T. Org. Lett.  2001,  3:  2345 ; and references cited therein
    CrossrefGoogle Scholar
  • 4c Yamazaki T. Hiraoka S. Sakamoto H. Kitazume T. Org. Lett.  2001,  3:  743 
    CrossrefGoogle Scholar
  • 5a Ichikawa J. Miyazaki S. Fujiwara M. Minami T. J. Org. Chem.  1995,  60:  2320 
    Article in Thieme ConnectGoogle Scholar
  • 5b Ichikawa J. Fujiwara M. Okauchi T. Minami T. Synlett  1998,  927 
    Article in Thieme ConnectGoogle Scholar
  • For reports on the Friedel-Crafts reaction of fluorinated allylic cations, see:
  • 6a Gyenes F. Purrington ST. Liu Y.-S. J. Org. Chem.  1999,  64:  1366 
    CrossrefGoogle Scholar
  • 6b Kobayashi Y. Nagai T. Kumadaki I. Takahashi M. Yamauchi T. Chem. Pharm. Bull.  1984,  32:  4382 
    CrossrefGoogle Scholar
  • 7 Ichikawa J. J. Fluorine Chem.  2000,  105:  257 
    CrossrefGoogle Scholar
  • 8 For reports on the protonation of 1,1-difluoroethylene with FSO3H·SbF5 to give 1,1,1-trifluoroethane or 1,1-difluoro-ethyl fluorosulfonate, see: Olah GA. Mo YK. J. Org. Chem.  1972,  37:  1028 
    CrossrefGoogle Scholar
  • 9 Bégué JP. Bonnet-Delpon D. Crousse B. Synlett  2004,  18 
    Article in Thieme ConnectGoogle Scholar
  • For recent reports on the cationic reactions conducted in HFIP, see:
  • 10a Ohwada A. Nara S. Sakamoto T. Kikugawa Y. J. Chem. Soc., Perkin Trans. 1  2001,  3064 
    CrossrefGoogle Scholar
  • 10b Bjurling E. Björkman A. Andersson C.-M. Organometallics  2001,  20:  990 
    CrossrefGoogle Scholar
  • 11a For reports on the synthesis of benzene-fused cyclic ketones, see: Gagnier SV. Larock RC. J. Am. Chem. Soc.  2003,  125:  4804 
    CrossrefGoogle Scholar
  • 11b See also: Cui D.-M. Zhang C. Kawamura M. Shimada S. Tetrahedron Lett.  2004,  1741 ; and references cited therein
    CrossrefGoogle Scholar
  • 11c For a review on the intramolecular aromatic Friedel-Crafts Reaction, see: Heaney H. In Comprehensive Organic Synthesis   Vol. 2:  Trost BM. Fleming I. Pergamon Press; Oxford: 1991.  Chap. 3.3.
    CrossrefGoogle Scholar
  • For recent examples, see:
  • 12a Vukics K. Fodor T. Fischer J. Fellegvári I. Lévai S. Org. Process Res. Dev.  2002,  6:  82 
    CrossrefPubMedGoogle Scholar
  • 12b Suh Y.-G. Shin D.-Y. Min K.-K. Hyun S.-S. Jung J.-K. Seo S.-Y. Chem. Commun.  2000,  1203 
    CrossrefPubMedGoogle Scholar
  • 12c Deshpande MN. Cain MH. Patel SR. Singam PR. Brown D. Gupta A. Barkalow J. Callen G. Patel K. Koops R. Chorghade M. Foote H. Pariza R. Org. Process Res. Dev.  1998,  2:  351 
    CrossrefPubMedGoogle Scholar
  • 12d Geen GR. Mann IS. Mullane MV. McKillop A. Tetrahedron  1998,  54:  9875 
    CrossrefPubMedGoogle Scholar
  • 12e Sugimoto H. Iimura Y. Yamanishi Y. Yamatsu K. J. Med. Chem.  1995,  38:  4821 
    CrossrefPubMedGoogle Scholar
  • 15 For discussions on the ability of halogens to stabilize carbocations, see: Christe KO. Zhang X. Bau R. Olah GA. Prakash GKS. Sheehy JA. J. Am. Chem. Soc.  2000,  122:  481 ; and references cited therein
    CrossrefGoogle Scholar
  • The spectroscopic data (1H, 13C NMR and IR) of 2a,b,d are in agreement with the reported data:
  • 16a Pouchert CJ. Behnke J. The Aldrich Library of 13 C and 1 H FT NMR Spectra   Aldrich Chemical Company, Inc.; Milwaukee: 1992. 
    Google Scholar
  • 16b Pouchert CJ. The Aldrich Library of Infrared Spectra 3rd ed.   Aldrich Chemical Company, Inc.; Milwaukee: 1981. 
    Google Scholar
13

The configuration of 1h was assigned by 1H NMR measurement. The 1H NMR spectrum for the major isomer of 1h exhibits a large geminal coupling constant (J gem = 13.4 Hz) between the protons Hax and Heq at C-3. Hax is coupled to the C-2 and C-4 protons with coupling constant values of 11.3 Hz and 4.6 Hz, which are consistent with typical axial-axial and axial-equatorial values, respectively. In the 1H NMR spectrum of the minor isomer of 1h, two large axial-axial coupling constants are observed between the C-3 axial proton and the C-2 proton and between the C-3 axial proton and the C-4 proton (J 32 = 14.0 Hz, J 34 = 11.9 Hz). Moreover, the observed NOEs between the C-2 axial proton and the methyl proton of the major isomer and between the C-2 axial proton and the C-4 axial proton of the minor isomer support this assignment. Stereochemistry was assigned for 2g on the basis of the proton coupling constants in a similar manner.

14

Vinyl fluoride 14 (X = F) was not detected by 19F NMR measurement of the reaction mixture.