Anodic Fluorination of 3-Substituted Benzofurans. Efficient Synthesis of 2-Fluoro- and 2,3-Difluoro-2,3-dihydrobenzofuran Derivatives

Kamal M. Dawood; Toshio Fuchigami

doi:10.1055/s-2003-41418

LETTER

Anodic Fluorination of 3-Substituted Benzofurans. Efficient Synthesis of 2-Fluoro- and 2,3-Difluoro-2,3-dihydrobenzofuran Derivatives [1]

Kamal M. Dawood^a, Toshio Fuchigami*^b
^a Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt
^b Department of Electronic Chemistry, Tokyo Institute of Technology, Nagatsuta, Midori-ku, Yokohama, Japan
Fax: +81(45)9245406; e-Mail: fuchi@echem.titech.ac.jp;

Abstract

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Abstract

Anodic fluorination of 3-methylbenzofuran and ethyl (3-benzofuranyl)acetate was successfully carried out to give mainly 2,3-difluoro-2,3-dihydrobenzofuran derivatives together with 2-fluoro-3-hydroxy derivatives as the minor products.

Key words

anodic fluorination - selective fluorination - benzofuran - stereoselectivity - regioselectivity

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Referenzen

References

1 Anodic Partial Fluorination of Organic Compounds. Part 69. Part 68: Shen Y. Suzuki K. Atobe M. Fuchigami T. J. Electroanal. Chem. 2003, 540: 189

2a Walker JA. Rossen K. Reamer RA. Volante RP. Reider PJ. Tetrahedron Lett. 1999, 40: 4917

2b Ganzalez AG. Barrera JB. Yanes AC. Diaz JG. Rodriguez EM. Phytochemistry 1989, 28: 2520

2c Carvalho CF. Sargent MV. J. Chem. Soc., Perkin Trans. 1 1984, 1605

3a Vinh TK. Ahmadi M. Delgado POL. Prerez SF. Walters HM. Smith HJ. Nicholls PJ. Simons C. Bioorg. Med. Chem. Lett. 1999, 9: 2105

3b Tomaszewski Z. Johnson MP. Haung X. Nichols DE. J. Med. Chem. 1992, 35: 2061

3c Ellingboe JW. Alessi TR. Dolak TM. Nguyen TT. Tomer JD. Guzzo F. Bagli JF. McCaleb ML. J. Med. Chem. 1992, 35: 1176

4a Biomedicinal Aspects of Fluorine Chemistry Filler R. Kobayashi Y. Kondansha and Elsevier Biomedical; Tokyo: 1982.

4b Welch JT. Eswarakrishnan S. Fluorine in Bioorganic Chemistry Wiley; New York: 1991.

4c Biomedical Frontiers of Fluorine Chemistry Ojima I. McCarthy JR. Welch JT. ACS Symposium Series 639, American Chemical Society; Washington DC: 1996.

4d Narizuka S. Fuchigami T. Bioorg. Med. Chem. Lett. 1995, 5: 1293

4e Hiyama T. Organofluorine Compounds: Chemistry and Applications Springer; Berlin: 2000.

5a Fuchigami T. In Advances in Electron-Transfer Chemistry Vol. 5: Mariano PS. JAI Press; Greenwich CT: 1999.

5b Fuchigami T. Higashiya S. Hou Y. Dawood KM. Rev. Heteroat. Chem. 1999, 19: 67

5c Fuchigami T. In Organic Electrochemistry 4th ed.: Lund H. Hammerich O. Dekker; New York: 2001. Chap. 25.

6a Dawood KM. Fuchigami T. J. Org. Chem. 2001, 66: 7691

6b Hou Y. Higashiya S. Fuchigami T. J. Org. Chem. 1999, 64: 3346

6c Hasegawa M. Ishii H. Fuchigami T. Tetrahedron Lett. 2002, 43: 1503

7 Meurs JH. Eilenberg W. Tetrahedron 1991, 47: 705

8

Compound 2a (cis): mp 54-55 °C. ¹H NMR (CDCl₃): δ = 1.31 (t, 3 H, J = 7.25 Hz), 3.06 (ddd, 1 H, J = 34.95, 17.31, 3.79 Hz), 3.45 (ddd, 1 H, J = 17.31, 10.06, 3.63 Hz), 4.42 (q, 2 H, J = 7.25 Hz), 6.51 (dd, 1 H, J = 57.87, 9.56 Hz), 7.07 (m, 2 H), 7.41 (m, 2 H). ¹⁹F NMR: δ = -56.09 (ddt, 1 F, J = 57.34, 18.49, 3.7 Hz), -66.89 (m, 1 F). ¹³C NMR (DEPT): δ = 14.12 (CH₃), 36.59 (dd, CH₂, J = 26.27, 3.9 Hz), 61.22 (CH₂), 111.48, 113.95 (dd, J = 235.87, 45.83 Hz), 122.86, 124.46, 132.90, (CH), 98.03 (dd, J = 183.33, 29.06 Hz), 123.32, 159.48, 167.85 (C). MS: m/z = 242 (M⁺), 222 (M⁺ - HF), 193, 165, 149, 127, 101, 84. Anal. Calcd for C₁₂H₁₂F₂O₃: C, 59.50; H, 4.99. Found: C, 59.36; H, 5.01.
Compound 2a (trans): yellow oil. ¹H NMR: δ = 1.23 (t, 3 H, J = 7.09 Hz), 2.91 (ddd, 1 H, J = 26.87, 15.83, 1.32 Hz), 3.19 (ddd, 1 H, J = 15.83, 9.93, 3.79 Hz), 4.17 (q, 2 H, J = 7.09 Hz), 6.39 (dd, 1 H, J = 60.84, 1.81 Hz), 6.96 (d, 1 H, J = 8.07 Hz), 7.08 (dd, 1 H, J = 7.58, 7.09 Hz), 7.38 (m, 2 H). ¹⁹F NMR: δ = -63.64 (ddd, 1 F, J = 61.03, 16.65, 3.70 Hz), -87.69 (m, 1 F). MS: m/z = 242 (M⁺), 222 (M⁺ - HF), 165, 149, 145, 101, 89. Anal. Calcd for C₁₂H₁₂F₂O₃: C, 59.50; H, 4.99. Found: C, 59.41; H, 5.09.
Compound 3a (cis): yellow oil. ¹H NMR: δ = 1.33 (t, 3 H, J = 7.25 Hz), 2.95 (dd, 1 H, J = 17.47, 3.95 Hz), 3.15 (dd, 1 H, J = 17.47, 5.44 Hz), 4.28 (q, 2 H, J = 7.25 Hz), 4.42 (s, 1 H), 6.16 (d, 1 H, J = 61.66 Hz), 6.97-7.10 (m, 2 H), 7.32-7.38 (m, 2 H). ¹⁹F NMR: δ = -50.71 (ddd, 1 F, J = 61.03, 5.55, 3.70 Hz). ¹³C NMR (DEPT): δ = 14.13 (CH₃), 37.63 (d, CH₂, J = 7.27 Hz), 61.53 (CH₂), 111.15, 116.88 (d, J = 239.22 Hz), 122.75, 123.85, 131.26 (CH), 80.12, 127.24, 158.28, 172.58 (C). MS: m/z = 240 (M⁺), 220 (M⁺ - HF), 204, 146, 133, 118, 105, 91, 77. Anal. Calcd for C₁₂H₁₃FO₄: C, 60.00; H, 5.45. Found: C, 60.20; H, 5.54.

9

Compound 2b (cis): colorless oil. ¹H NMR: δ = 1.83 (dd, 3 H, J = 21.27, 4.45 Hz), 6.10 (dd, 1 H, J = 60.18, 12.36 Hz), 7.06 (m, 2 H), 7.40 (m, 2 H). ¹⁹F NMR: δ = -56.97 (dd, 1 F, J = 62.88, 16.65 Hz), -67.21 (m, 1 F). MS: m/z = 170 (M⁺), 155, 122, 96, 75, 63, 51. Anal. Calcd for C₉H₈F₂O: C, 63.53; H, 4.74. Found: C, 63.38; H, 4.85.& linebreak;Compound 2b (trans): colorless oil. ¹H NMR: δ = 1.80 (dd, 3 H, J = 21.10, 1.35 Hz), 6.10 (dd, 1 H, J = 61.99, 1.86 Hz), 7.06 (m, 2 H), 7.36 (m, 2 H). ¹⁹F NMR: δ = -62.24 (dd, 1 F, J = 61.04, 13.13 Hz), -84.55 (m, 1 F). MS: m/z = 170 (M⁺), 155, 127, 122, 101, 96, 75, 63, 51.
Compound 3b (cis): mp 66-67 °C. ¹H NMR: δ = 1.66 (d, 3 H, J = 4.28 Hz), 2.18 (s, 1 H), 5.92 (d, 1 H, J = 61.83 Hz), 6.90-7.08 (m, 2 H), 7.29-7.35 (m, 2 H). ¹⁹F NMR: δ =
-52.27 (dm, 1 F, J = 81.03 Hz). ¹³C NMR (DEPT): δ = 19.10 (CH₃, d, J = 6.71 Hz), 111.18, 117.42 (d, J = 240.35 Hz), 122.80, 123.19, 131.02 (CH), 79.70, 129.66, 157.99 (C). MS: m/z = 168 (M⁺), 153, 133, 105, 91, 77, 65, 51. Anal. Calcd for C₉H₉FO₂: C, 64.28; H, 5.39. Found: C, 64.29; H, 5.19.

10a Umemoto T. Tomizawa J. Bull. Chem. Soc. Jpn. 1986, 59: 3625

10b Umemoto T. Tomizawa J. J. Org. Chem. 1995, 60: 6563

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Compound 5a: mp 70-71 °C (hexane). ¹H NMR (CDCl₃):
δ = 1.35 (t, 3 H, J = 7.25 Hz), 4.29 (q, 2 H, J = 7.25 Hz), 6.44 (dd, 1 H, J = 5.60, 1.32 Hz), 7.04 (m, 2 H), 7.20 (dd, 1 H, J = 58.36, 1.32 Hz), 7.41 (dd, 1 H, J = 8.10, 7.58 Hz), 7.51 (d, 1 H, J = 7.58 Hz). ¹⁹F NMR: δ = -41.75 (dd, 1 F, J = 59.18, 5.55 Hz). ¹³C NMR (DEPT): δ = 14.30 (CH₃), 61.01 (CH₂), 108.62 (d, CH, J = 232.51 Hz), 111.38, 114.07, 122.33, 122.72, 133.96 (CH), 121.49, 122.74, 161.57, 169.50 (C). MS: m/z = 222 (M⁺), 193, 177, 149, 101, 84. Anal. Calcd for C₁₂H₁₁FO₃: C, 64.86; H, 4.99. Found: C, 64.81; H, 4.97.
Compound 6a: yellow oil. ¹H NMR (CDCl₃): δ = 1.25 (t, 3 H, J = 7.25 Hz), 1.37-1.47 (m, 2 H), 1.52-1.63 (m, 4 H), 2.41-2.60 (m, 4 H), 4.20 (q, 2 H, J = 7.25 Hz), 4.80 (d, 1 H, J = 0.82 Hz), 7.26 (m, 2 H), 7.45 (dd, 1 H, J = 7.42, 1.32 Hz), 7.66 (s, 1 H), 7.81 (dd, 1 H, J = 7.58, 1.48 Hz). ¹³C NMR (DEPT): δ = 14.35 (CH₃), 24.27, 26.20, 51.70, 60.77 (CH₂), 65.24, 111.25, 121.18, 122.50, 124.30, 143.68 (CH), 115.95, 127.12, 155.16, 170.48 (C). MS: m/z = 288 (M⁺ + 1), 287 (M⁺), 222, 214, 131, 84. Anal. Calcd for C₁₇H₂₁NO₃: C, 71.06; H, 7.37; N, 4.87. Found: C, 70.74; H, 7.26; N, 4.74.