Synthesis 2002(13): 1917-1936
DOI: 10.1055/s-2002-33912
FEATUREARTICLE
© Georg Thieme Verlag Stuttgart · New York

The Nucleophilic 5-endo-trig Cyclization of 1,1-Difluoro-1-alkenes: Ring-Fluorinated Hetero- and Carbocycle Synthesis and Remarkable Effect of the Vinylic Fluorines on the Disfavored Process

Junji Ichikawa*, Yukinori Wada, Masaki Fujiwara, Kotaro Sakoda
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;
Further Information

Publication History

Received 21 May 2002
Publication Date:
09 September 2002 (online)

Abstract

The disfavored 5-endo-trig cyclizations have been accomplished for 1,1-difluoro-1-alkenes with nitrogen, oxygen, sulfur, and carbon nucleophiles by taking advantage of the properties of fluorine. β,β-Difluorostyrenes bearing tosylamido, hydroxy, or methylsulfinyl group at the o-position undergo intramolecular nucleophilic substitution with a loss of the vinylic fluorine, leading to 2-fluorinated indole, benzo[b]furan, and benzo[b]thiophene in high yields. 1,1-Difluoro-1-butenes bearing homoallylic tosyl­amido, hydroxy, mercapto, or iodomethyl group also successfully cyclize via a 5-endo-trig process with the in situ generated intramolecular nucleophiles to afford 2-fluoro-2-pyrroline, 5-fluoro-2,3-dihydrofuran, 5-fluoro-2,3-dihydrothiophene, and 1-fluorocyclo-pentene. The two vinylic fluorines proved to be essential and play a critical role in these ‘anti-Baldwin’ cyclizations.

    References

  • 1a Baldwin JE. J. Chem. Soc., Chem. Commun.  1976,  734 
  • 1b Baldwin JE. Cutting J. Dupont W. Kruse L. Silberman L. Thomas RC. J. Chem. Soc., Chem. Commun.  1976,  736 
  • 1c Baldwin JE. Thomas RC. Kruse LI. Silberman L. J. Org. Chem.  1977,  42:  3846 
  • For recent reports see:
  • 2a Jones AD. Knight DW. Hibbs DE. J. Chem. Soc., Perkin Trans. 1  2001,  1182 ; and references cited therein
  • 2b Bravo F. Kassou M. Castillón S. Tetrahedron Lett.  1999,  40:  1187 
  • 2c Andrey O. Ducry L. Landais Y. Planchenault D. Weber V. Tetrahedron Lett.  1997,  40:  3267 ; and references cited therein
  • 2d Kimura M. Harayama H. Tanaka S. Tamaru Y. J. Chem. Soc., Chem. Commun.  1994,  2531 ; and references cited therein
  • For recent reports see:
  • 3a Parsons AF. C. R. Acad. Sci.  2001,  4:  391 ; and references cited therein
  • 3b Bommezijn S. Martin CG. Kennedy AR. Lizos D. Murphy JA. Org. Lett.  2001,  3:  3405 ; and references cited therein
  • 3c Ishibashi H. Sato T. Ikeda M. Synthesis  2002,  695 
  • 4a Caldwell JJ. Craig D. East SP. Synlett  2001,  1602 ; and references cited therein
  • 4b Dell’Erba C. Mugnoli A. Novi M. Pani M. Petrillo G. Tavani C. Eur. J. Org. Chem.  2000,  903 ; and references cited therein
  • 4c Auvray P. Knochel P. Normant JF. Tetrahedron Lett.  1985,  26:  4455 
  • 4d Beak P. Wilson KD. J. Org. Chem.  1986,  51:  4627 ; and references cited therein
  • 4e Padwa A. Yeske PE. J. Am. Chem. Soc.  1988,  110:  1617 
  • 4f Grigg R. Kemp J. Malone JF. Rajviroongit S. Tangthongkum A. Tetrahedron  1988,  44:  5361 
  • 4g Tsuge O. Kanemasa S. Yamada T. Matsuda K. J. Org. Chem.  1987,  52,:  2523 
  • 4h Thorimbert S. Malacria M. Tetrahedron Lett.  1998,  39:  9659 
  • 4i Gao J. Rusling JF. J. Org. Chem.  1998,  63:  218 
  • 5a Ichikawa J. Wada Y. Okauchi T. Minami T. Chem. Commun.  1997,  1537 
  • 5b Ichikawa J. Fujiwara M. Wada Y. Okauchi T. Minami T. Chem. Commun.  2000,  1887 
  • 5c Ichikawa J. Wada Y. Sakoda K. Chem. Lett.  2002,  282 
  • After our findings on the unusual reactivity of 1,1-difluoro-1-alkenes in 5-endo-trig cyclization,5a examples based on the same concept have been reported:
  • 6a Yamazaki T. Hiraoka S. Sakamoto J. Kitazume T. J. Phys. Chem. A  1999,  103:  6820 
  • 6b Wang Z.-G. Hammond GB. J. Org. Chem.  2000,  65:  6547 
  • 6c Coe PL. Burdon J. Haslock IB. J. Fluorine Chem.  2000,  102:  43 
  • 6d Volle J.-N. Schlosser M. Eur. J. Org. Chem.  2000,  823 
  • 7a Smart BE. In Organofluorine Chemistry Principles and Commercial Applications   Banks RE. Smart BE. Tatlow JC. Plenum; New York: 1994.  p.57 
  • 7b Lee VJ. In Comprehensive Organic Synthesis   Vol. 4:  Trost BM. Pergamon; Oxford: 1991.  p.69 
  • 8 Ichikawa J. Kobayashi M. Noda Y. Yokota N. Amano K. Minami T. J. Org. Chem.  1996,  61:  2763 
  • For related ring constructions of in situ generated 1,1-difluoro-1-alkenes see:
  • 9a Strekowski L. Kiselyov AS. Hojjat M. J. Org. Chem.  1994,  59:  5886 ; and references cited therein
  • 9b Kiselyov AS. Strekowski L. Tetrahedron Lett.  1994,  35:  7597 
  • 10a Silvester MJ. Adv. Heterocycl. Chem.  1994,  59:  1 
  • 10b Silvester MJ. Aldrichimica Acta  1991,  24:  31 
  • 10c Organofluorine Chemistry Principles and Commercial Applications   Banks RE. Smart BE. Tatlow JC. Plenum; New York: 1994. 
  • For the 6-endo-trig cyclization of 1,1-difluoro-1-alkenes see:
  • 11a Wada Y. Ichikawa J. Katsume T. Nohiro T. Okauchi T. Minami T. Bull. Chem. Soc. Jpn.  2001,  74:  971 
  • 11b Burdon J. Coe PL. Haslock IB. Powell RL. J. Fluorine Chem.  1997,  85:  151 
  • 12 Ichikawa J. J. Fluorine Chem.  2000,  105:  257 ; and references cited therein
  • 13 Ichikawa J. Minami T. Sonoda T. Kobayashi H. Tetrahedron Lett.  1992,  33:  3779 
  • 14 Ichikawa J. Fujiwara M. Nawata H. Okauchi T. Minami T. Tetrahedron Lett.  1996,  37:  8799 
  • 15 Ichikawa J. Ikeura C. Minami T. Synlett  1992,  739 
  • 16a Mitsunobu O. Synthesis  1981,  1 
  • 16b Henry JR. Marcin LR. McIntosh MC. Scola PM. Harris GD. Weinreb SM. Tetrahedron Lett.  1989,  30:  5709 
  • 17 Roush WR. Dtraub JA. Brown RJ. J. Org. Chem.  1987,  52:  5127 
  • 18 Hayashi S. Nakai T. Ishikawa N. Burton DJ. Naae DG. Kesling HS. Chem. Lett.  1979,  983 
  • 19a Kitazume T. Ohnogi T. Synthesis  1988,  615 
  • 19b Fuchikami T. Shibata Y. Suzuki Y. Tetrahedron Lett.  1986,  27:  3173 
  • 20 Hutchinson DK. Fuchs PL. J. Am. Chem. Soc.  1987,  109:  4930 
  • For examples where N-substituents played an important role see:
  • 21a Tarnchompoo B. Thebtaranonth C. Thebtaranonth Y. Tetrahedron Lett.  1987,  28:  6675 
  • 21b Padwa A. Norman BH. J. Org. Chem.  1990,  55:  4801 
  • 22 For the synthesis of 2- and 3-fluoroindoles see: Torres JC. Garden SJ. Pinto AC. da Silva FSQ. Boechat N. Tetrahedron  1999,  55:  1881 ; and references cited therein.
  • For the synthesis of 2- and 3-fluorobenzo[b]furans see:
  • 23a Martín-Santamaría S. Carroll MA. Carroll CM. Carter CD. Pike VW. Rzepa HS. Widdowson DA. Chem. Commun.  2000,  649 
  • 23b Barton DHR. Hesse RH. Jackman GP. Pechet MM. J. Chem. Soc., Perkin Trans. 1  1977,  2604 
  • 23c Bailey J. Plevey RG. Tatlow JC. Tetrahedron Lett.  1975,  869 
  • For the synthesis of 2- and 3-fluorobenzo[b]thiophenes see:
  • 24a Shirley IM. J. Fluorine Chem.  1994,  66:  51 
  • 24b Nussbaumer P. Petranyi G. Stütz A. J. Med. Chem.  1991,  34:  65 
  • 24c Bensoam J. Mathey F. Tetrahedron Lett.  1977,  2797 
  • For the electrocyclization of 1,1-difluoro-1-alkenes see:
  • 25a Chambers RD. Greenhall MP. J. Chem. Soc., Chem. Commun.  1990,  1128 
  • 25b Burger K. Helmreich B. J. Chem. Soc., Chem. Commun.  1992,  348 
  • 26 For the synthesis of fluorofurans see: Forrest AK. O’Hanlon PJ. Tetrahedron Lett.  1995,  36:  2117 ; and references cited therein
  • For the synthesis of fluoropyrroles see:
  • 27a Tajima T. Ishii H. Fuchigami T. Tetrahedron Lett.  2001,  42:  4857 
  • 27b Novikov MS. Khlebnikov AF. Sidorina ES. Kostikov RR. J. Fluorine Chem.  1998,  90:  117 ; and references cited therein
  • 27c Qiu Z.-M. Burton DJ. Tetrahedron Lett.  1995,  36:  5119 ; and references cited therein
  • 27d Leroy J. Wakselman C. Tetrahedron Lett.  1994,  35:  8605 ; and references cited therein
  • 27e Barnes K. Hu Y. Hunt D. Synth. Commun.  1994,  24:  1749 
  • For the synthesis of fluorothiophenes see:
  • 28a Chambers RJ. Marfat A. Synth. Commun.  2000,  30:  3629 
  • 28b Kobarfard F. Kauffman JM. J. Heterocycl. Chem.  1999,  36:  1247 
  • 28c Andrés DF. Laurent EG. Marquet BS. Tetrahedron Lett.  1997,  38:  1049 ; and references cited therein
  • 28d Burger K. Helmreich B. Heterocycles  1994,  39:  819 ; and references cited therein
  • 29 For the intramolecular carbolithiation of fluorine-free alkenes see: Yus M. Oritz R. Huerta FF. Tetrahedron Lett.  2002,  43:  2957 ; and references cited therein
  • 30 Strobach DR. Boswell GA. J. Org. Chem.  1971,  36:  818 
  • 31a Bailey WF. Punzalan ER. J. Org. Chem.  1990,  55:  5404 
  • 31b Negishi E. Swanson DR. Rousset CJ. J. Org. Chem.  1990,  55:  5406 
  • 32 Topolsky M. J. Org. Chem.  1995,  60:  5588