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Synlett 2008(3): 343-346  
DOI: 10.1055/s-2008-1032042
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Practical Synthetic Route to Benzofuro[2,3-b]pyridine and Trifluoromethyl-α-carbolines

Viktor O. Iaroshenko*a,b, Ulrich Grotha, Nadiya V. Kryvokhyzhac, Samra Obeida, Andrei A. Tolmachevb,d, Thomas Wescha
a Fachbereich Chemie, Universität Konstanz, Fach M-720, Universitätsstraße 10, 78457 Konstanz, Germany
Fax: +49(7531)884424; e-Mail: yva108@yahoo.co.uk;
b National Taras Shevchenko University, 62 Volodymyrska st., Kyiv 33, 01033, Ukraine
c Department of Chemistry, University of Glasgow, University Avenue, Glasgow, G12 8QQ, UK
d ‘Enamine Ltd.’, 23 A. Matrosova st., 01103 Kyiv, Ukraine
Further Information

Publication History

Received 25 September 2007
Publication Date:
16 January 2008 (online)

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Abstract

In situ generated benzofuran-2-amine reacts with 1,3-CCC-dielectrophiles, such as CF3-containing β-diketones, 3-formylchromone, methyl-2,4-dioxopentanoate and pentafluoro­benzaldehyde, and the reaction leads to the formation of benzofuro[2,3-b]pyridine ring system. By using a similar approach 4-trifluoromethyl-α-carbolines were synthesized starting from indole-2-amine.

Key words

furanamine - indoleamine - pyridine - annulation - electrophilic aromatic substitution

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18

2-Methyl-4-(trifluoromethyl)benzofuro[2,3- b ]pyridine (5a): colorless solid (1.13 g, 90%); mp 115-117 °C; R f = 0.65 (EtOAc-hexane, 1:2). 1H NMR (400 MHz, DMSO-d 6): δ = 2.68 (s, 3 H), 7.50 (t, 3 J HH = 8.0 Hz, 1 H), 7.66 (t, 3 J HH = 8.0 Hz, 1 H), 7.73 (s, 1 H), 7.83 (d, 3 J HH = 8.0 Hz, 1 H), 7.99 (d, 3 J HH = 8.0 Hz, 1 H). 13C NMR (100.5 MHz, DMSO-d 6): δ = 24.4, 109.8, 112.7, 115.5, 119.7, 123.4, 123.7 (1 J CF = 275 Hz), 124.7, 126.7, 129.9 (2 J CF = 35 Hz), 154.5, 158.1, 163.1. 19F NMR (376.2 MHz, DMSO-d 6): δ = -63.5. MS: m/z (%) = 242 (14) [M+ + 1], 241 (100) [M+], 210 (37), 182 (41). Anal. Calcd for C13H8F3NO: C, 62.16; H, 3.21; N, 5.58. Found: C, 62.18; H, 3.20; N, 5.57.

19

General Procedure for the Synthesis of Furo[2,3- b ]pyridines 5, 9, 11, and benzofuro[2,3- b ]quinoline 13: To a boiling solution of AcOH (250 mL) and H2O (10 mL; temperature in the oil bath was about 135 °), a mixture of a dielectrophile (5 mmol) and 2-isocyanatobenzofuran (1.99 g, 12.5 mmol) in absolute DMF (50 mL) was dropped very slowly through the condenser. After the addition was completed the mixture was refluxed for further 3 h. After evaporation of the solvent, the residue was subjected to column chromatography over silica gel, or recrystallized from appropriate solvent.

23

7,8,9,10-Tetrafluorobenzofuro[2,3- b ]quinoline (13): colorless solid (1.05 g, 72%); mp 235-237 °C (i-PrOH). 1H NMR (400 MHz, DMSO-d 6): δ = 7.55 (t, 3 J HH = 8.0 Hz, 1 H), 7.74 (t, 3 J HH = 8.0 Hz, 1 H), 7.81 (d, 3 J HH = 8.0 Hz, 1 H), 8.40 (d, 3 J HH = 8.0 Hz, 1 H), 9.35 (s, 1 H). MS: m/z (%) = 292 (17) [M+ + 1], 291 (100) [M+], 262 (10), 145 (10). Anal. Calcd for C15H5F4NO: C, 61.87; H, 1.73; N, 4.81. Found: C, 61.85; H, 1.74; N, 4.82.

25

4-(Difluoromethyl)-2-methylbenzofuro[2,3- b ]pyridine (14a): colorless solid (0.99 g, 85%); mp 112-113 °C; R f = 0.5 (EtOAc-hexane, 1:2). 1H NMR (400 MHz, CDCl3): δ = 2.72 (s, 3 H), 7.04 (t, 2 J HF = 56 Hz, 1 H), 7.31 (s, 1 H), 7.39 (t, 3 J HH = 8.0 Hz, 1 H), 7.53 (t, 3 J HH = 8.0 Hz, 1 H), 7.63 (d, 3 J HH = 8.0 Hz, 1 H), 8.01 (d, 3 J HH = 8.0 Hz, 1 H). 13C NMR (100.5 MHz, CDCl3): δ = 24.5, 110.8, 112.4 (1 J CF = 240 Hz), 113.1, 115.5, 120.9, 123.4, 124.3, 128.6, 136.8 (2 J CF = 26 Hz), 154.6, 157.0, 163.4. 19F NMR (376.2 MHz, DMSO-d 6): δ = -115.3 (d, 2 J HF = 56 Hz, 2 F). MS: m/z (%) = 234 (15) [M+ + 1], 233 (100) [M+], 182 (16). Anal. Calcd for C13H9F2NO: C, 66.95; H, 3.89; N, 6.01. Found: C, 66.94; H, 3.89; N, 6.02.