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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
Further Information

Publication History

Received 5 March 2004
Publication Date:
10 May 2004 (online)

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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.

Key words

isocyanides - fluorinated alkenes - electron transfer - cyclizations - fluorinated quinolines

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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).