Synlett 2004(7): 1219-1222  
DOI: 10.1055/s-2004-825599
LETTER
© Georg Thieme Verlag Stuttgart · New York

C-C Bond Formation between Isocyanide and β,β-Difluoroalkene Moieties via Electron Transfer: Fluorinated Quinoline and Biquinoline Syntheses

Junji Ichikawa*a, Takashi Moria, Hiroyuki Miyazakib, Yukinori Wadaa
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
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Publikationsverlauf

Received 5 March 2004
Publikationsdatum:
10. Mai 2004 (online)

Abstract

o-Isocyano-substituted β,β-difluorostyrenes are reduced with tributylstannyllithium to the anionic species, which in turn undergo intramolecular substitution of the isocyano carbon for the vinylic fluorine, followed by reaction with electrophiles or self-coupling to afford 2,4-disubstituted 3-fluoroquinolines or 4,4′-di­substituted 3,3′-difluoro-2,2′-biquinolines, respectively, in good yield.

    References

  • 1 Yates FS. In Comprehensive Heterocyclic Chemistry   Vol. 2:  Katritzky AR. Rees CW. Pergamon; New York: 1984.  Chap. 2.09.
  • For reviews, see:
  • 2a Silvester MJ. Adv. Heterocycl. Chem.  1994,  1:  59 
  • 2b Silvester MJ. Aldrichimica Acta  1991,  24:  31 
  • 2c Organofluorine Chemistry, Principles and Commercial Applications   Banks RE. Smart BE. Tatlow JC. Plenum; New York: 1994. 
  • 3 Hirano Y. Uehara M. Saeki K. Kato T. Takahashi K. Mizutani T. J. Health Sci.  2002,  48:  118 ; and references therein
  • 4 Kato T. Saeki K. Kawazoe Y. Hakura A. Mutat. Res.  1999,  439:  149 ; and references therein
  • 5a Mongin F. Mojovic L. Guillamet B. Trécourt F. Quéguiner G. J. Org. Chem.  2002,  67:  8991 
  • 5b Arzel E. Rocca P. Marsais F. Godard A. Quéguiner G. Tetrahedron  1999,  55:  12149 
  • For the synthesis of fluoroquinolines, see:
  • 6a Wada Y. Mori T. Ichikawa J. Chem. Lett.  2003,  1000 
  • 6b Ichikawa J. Wada Y. Miyazaki H. Mori T. Kuroki H. Org. Lett.  2003,  5:  1455 
  • 6c Chambers RD. Parsons M. Sandford G. Skinner CJ. Atherton MJ. Moilliet JS. J. Chem. Soc., Perkin Trans. 1  1999,  803 ; and references therein
  • 6d Strekowski L. Kiselyov AS. Hojjat M. J. Org. Chem.  1994,  59:  5886 
  • 6e Shi G.-Q. Takagishi S. Schlosser M. Tetrahedron  1994,  50:  1129 
  • For the synthesis of 2,4-disubstituted quinolines, see:
  • 7a Wolf C. Lerebours R. J. Org. Chem.  2003,  68:  7077 
  • 7b Kobayashi K. Yoneda K. Mano M. Morikawa O. Konishi H. Chem. Lett.  2003,  76 
  • 7c Huma HZS. Halder R. Kalra SS. Das J. Iqbal J. Tetrahedron Lett.  2002,  43:  6485 
  • See also for recent reports on the construction of quinoline framework:
  • 7d Kim JN. Chung YM. Im YJ. Tetrahedron Lett.  2002,  43:  6209 
  • 7e Cho CS. Oh BH. Kim JS. Kim T.-J. Shim SC. Chem. Commun.  2000,  1885 ; and references therein
  • For the synthesis of quinolines from aryl isocyanides, see the following and references cited therein:
  • 7f Kobayashi K. Yoneda K. Mizumoto T. Umakoshi H. Morikawa O. Konishi H. Tetrahedron Lett.  2003,  44:  473 
  • 7g Curran DP. Du W. Org. Lett.  2002,  4:  3215 
  • 7h Suginome M. Fukuda T. Ito Y. Org. Lett.  1999,  1:  1977 
  • 8a Smart BE. In Organofluorine Chemistry, Principles and Commercial Applications   Banks RE. Smart BE. Tatlow JC. Plenum; New York: 1994.  Chap. 3.
  • 8b Lee VJ. In Comprehensive Organic Synthesis   Vol. 4:  Trost BM. Fleming I. Pergamon; Oxford: 1991.  Chap. 1.2.
  • 9a Gros P. Fort Y. Eur. J. Org. Chem.  2002,  3375 ; and references therein
  • 9b Gros P. Fort Y. Caubère P. J. Chem. Soc., Perkin Trans. 1  1997,  3597 
  • 10 McCombie SW. In Comprehensive Organic Synthesis   Vol. 8:  Trost BM. Fleming I. Pergamon; Oxford: 1991.  Chap. 4.2.
  • Under free radical conditions with n-Bu3SnH or EtSH, this type of C-C bond formation is well known in the Fukuyama indole synthesis. See:
  • 11a Fukuyama T. Chen X. Peng G. J. Am. Chem. Soc.  1994,  116:  3127 
  • 11b Tokuyama H. Fukuyama T. Chem. Rec.  2002,  2:  37 
  • 13 The cyclization similarly proceeded even in the dark. For electron transfer from triorganostannyl anions, see: Yammal CC. Podesta JC. Rossi RA. J. Org. Chem.  1992,  57:  5720 
  • For recent reports on biquinoline synthesis, see:
  • 14a Uchida Y. Echikawa N. Oae S. Heteroat. Chem.  1994,  5:  409 
  • 14b Fort Y. Becker S. Caubère P. Tetrahedron  1994,  50:  11893 
  • Biquinolines are widely used as bulky, chelating nitrogen ligands. See for example:
  • 15a Bhattacharyya R. Drago RS. Abboud KA. Inorg. Chem.  1997,  36:  2913 
  • 15b Gogoll A. Gomes J. Bergkvist M. Grennberg H. Organometallics  1995,  14:  1354 
  • 15c Kubow SA. Marmion ME. Takeuchi KJ. Inorg. Chem.  1988,  27:  2761 
  • See also for a chiral 2,2′-biquinoline N,N′-dioxide as an asymmetric catalyst:
  • 15d Nakajima M. Saito M. Shiro M. Hashimoto S. J. Am. Chem. Soc.  1998,  120:  6419 
  • 20 Shimano M. Meyers AI. Tetrahedron Lett.  1994,  35:  7727 
12

The redox potential of 1a was measured by cyclic voltam-metry. A reduction peak of 1a was observed at -2.79 V [1 mM in THF; supporting electrolyte: 0.1 M n-Bu4NClO4; working electrode: glassy carbon; counter electrode: platinum wire; reference electrode: Ag/AgCl (E1/2 (ferrocene/ferricinium) = +0.26 V) at 25 °C; scan rate: 100 mVs-1].

16

4-Butyl-3-fluoroquinoline ( 4a): To a solution of (n-Bu3Sn)2 (0.51 mL, 1.0 mmol) in THF (3 mL) was added n-BuLi (0.64 mL, 1.59 M in hexane, 1.0 mmol) over 15 min at 0 °C. To the resulting solution was added 1a (75 mg, 0.34 mmol) in THF (3 mL) dropwise at -78 °C. The reaction mixture was stirred at -78 °C for 1 h. The reaction was quenched with phosphate buffer (pH 7), and organic materials were extracted with Et2O (10 mL × 3). The combined extracts were washed with brine and then dried over MgSO4. After removal of the solvent under reduced pressure, the residue was purified by preparative TLC (hexane-EtOAc, 5:1) to give 4a (55 mg, 80%) as a pale yellow oil. 1H NMR (500 MHz, CDCl3): δ = 0.97 (3 H, t, J = 7.4 Hz), 1.46 (2 H, tq, J = 7.4, 7.4 Hz), 1.64-1.72 (2 H, m), 3.08 (2 H, td, J = 7.8 Hz, J HF = 1.8 Hz), 7.59 (1 H, dd, J = 8.0, 8.0 Hz), 7.66 (1 H, ddd, J = 8.0, 8.0, 0.8 Hz), 7.98 (1 H, dd, J = 8.0, 0.8 Hz), 8.11 (1 H, dd, J = 8.0, 0.8 Hz), 8.74 (1 H, d, J HF = 1.2 Hz). 13C NMR (125 MHz, CDCl3): δ = 13.8, 22.8, 23.9 (d, J CF = 3 Hz), 31.8, 123.5 (d, J CF = 6 Hz), 127.2, 127.9 (d, J CF = 3 Hz), 128.0 (d, J CF = 4 Hz), 130.3, 131.6 (d, J CF = 12 Hz), 141.0 (d, J CF = 29 Hz), 145.5 (d, J CF = 2 Hz), 154.3 (d, J CF = 251 Hz). 19F NMR (471 MHz, CDCl3/C6F6): δF = 28.6 (s). IR (neat): 2960, 2931, 1512, 1464, 1379, 1323, 1225, 1142, 760, 665 cm-1. HRMS: calcd for C13H14NF: 203.1110 (M+); found: 203.1128.

17

4,4′-Dibutyl-3,3′-difluoro-2,2′-biquinoline (5a): To a solution of (n-Bu3Sn)2 (0.44 mL, 0.86 mmol) in THF (3 mL) was added n-BuLi (0.54 mL, 1.60 M in hexane, 0.86 mmol) over 15 min at 0 °C. The resulting solution (n-Bu3SnLi in THF) was added to a solution of 1a (76 mg, 0.35 mmol) in THF (3 mL) over 1 h at 0 °C. The reaction mixture was stirred at r.t. for 1 h. The reaction was quenched with phosphate buffer (pH 7), and organic materials were extracted with Et2O (10 mL × 3). The combined extracts were washed with brine and then dried over MgSO4. After removal of the solvent under reduced pressure, the residue was purified by preparative TLC (hexane-EtOAc, 5:1) to give 5a (41 mg, 59%) as a pale yellow oil. 1H NMR (500 MHz, CDCl3): δ = 1.00 (6 H, t, J = 7.5 Hz), 1.51 (4 H, tq, J = 7.5, 7.5 Hz), 1.72-1.80 (4 H, m), 3.20 (4 H, t, J = 7.8 Hz), 7.66 (2 H, ddd, J = 8.0, 8.0, 1.2 Hz), 7.72 (2 H, ddd, J = 8.0, 8.0, 1.5 Hz), 8.06 (2 H, dd, J = 8.0, 8.0 Hz), 8.31 (2 H, dd, J = 8.0, 8.0 Hz). 13C NMR (125 MHz, CDCl3): δ = 13.8, 22.7, 24.1, 31.8, 123.3, 127.6, 128.2, 128.5, 130.9, 132.8 (dd, J CF = 10, 3 Hz), 145.2 (dd, J CF = 13, 4 Hz), 145.3, 152.9 (dd, J CF = 256, 2 Hz). 19F NMR (471 MHz, CDCl3/C6F6): δF = 31.0 (s). IR (neat): 2958, 2929, 2872, 1504, 1456, 1377, 1338, 1221, 1188, 1144, 762 cm-1. HRMS: calcd for C26H26N2F2: 404.2064 (M+); found: 404.2057.

18

The corresponding 2-quinolyltin was not detected in the reaction mixture by 19F NMR. Over the course of the reaction, the corresponding ditin and tin hydride were produced probably via the tin radical.

19

The formation of biquinoline 5 via the reaction of 3 and 1 was confirmed as follows: When quinolyl anion 3a (R =
n-Bu), generated by the addition of 1a to n-Bu3SnLi, was reacted with 0.8 equiv of 1b (R = Et), unsymmetrical 4-butyl-4′-ethyl-3,3′-difluoro-2,2′-biquinoline was obtained in 59% yield (based on the consumed 1b).