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Synlett 2009(1): 59-62  
DOI: 10.1055/s-0028-1087476
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Tandem Meinwald Rearrangement-Fischer Indolisation: A One-Pot Conversion of Epoxides into Indoles

James R. Donald, Richard J. K. Taylor*
Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK
Fax: +44(1904)434523; e-Mail: rjkt1@york.ac.uk;
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Publication History

Received 6 October 2008
Publication Date:
12 December 2008 (online)

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Abstract

A tandem Sc(OTf)3-mediated Meinwald epoxide re­arrangement-Fischer indole synthesis is reported. Optimisation and scope and limitation studies are described. In addition, preliminary investigations to develop a telescoped epoxidation-Meinwald re­arrangement-Fischer indole sequence are outlined.

Key words

aldehydes - epoxides - indoles - rearrangements - tandem reactions

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14

All novel compounds were fully characterized.
3-(2′-Benzofuranyl) indole (6a)
Pale orange microcrystals; mp 162-163 ˚C (heptane); R f  = 0.27 (PE-Et2O, 4:1). ¹H NMR (400 MHz, CDCl3): δ = 8.33 (br s, 1 H), 8.05-8.00 (m, 1 H), 7.71 (d, J = 2.5 Hz, 1 H), 7.57-7.52 (m, 1 H), 7.49-7.45 (m, 1 H), 7.44-7.39 (m, 1 H), 7.29-7.24 (m, 2 H), 7.23-7.16 (m, 2 H), 6.91 (s, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 154.0, 152.9, 136.6, 129.9, 124.6, 123.3, 123.12, 123.08, 122.8, 121.1, 120.4, 120.3, 111.7, 110.8, 108.8, 99.7. IR (neat): νmax = 3399, 2918, 2850, 1623, 1453, 1427, 1358, 1249, 1100 cm-¹. MS (EI+): m/z (%) = 233 (97) [M+ ], 135 (38), 97 (37), 95 (50), 93 (37), 91 (52), 83 (37), 81 (63), 79 (50), 71 (51), 69 (71), 67 (100), 57 (73), 55 (91), 43 (48), 41 (52). HRMS (EI+): m/z calcd for C16H11NO: 233.0841; Found: 233.0842 [M+ ] (0.4 ppm error).
1-Methyl-3-(2′-benzofuranyl) indole (6b) Colourless microcrystals; mp 109-110 ˚C (i-PrOH); R f  = 0.44 (PE-Et2O, 7:3). ¹H NMR (400 MHz, CDCl3): δ = 8.06 (dd, J = 8.0, 1.0 Hz, 1 H), 7.62 (s, 1 H), 7.60-7.57 (m, 1 H), 7.54-7.49 (m, 1 H), 7.40 (dd, J = 7.5, 1.5 Hz, 1 H), 7.35 (app. td, J = 7.5, 1.5 Hz, 1 H), 7.31 (app. td, J = 7.5, 1.5 Hz, 1 H), 7.27-7.22 (m, 2 H), 6.91 (d, J = 0.5 Hz, 1 H) 3.85 (s, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 154.0, 153.1, 137.5, 130.0, 127.7, 125.1, 123.1, 122.8, 122.6, 120.7, 120.5, 120.1, 110.7, 109.9, 107.0, 99.1, 33.2. IR (neat): νmax = 3053, 2924, 2853, 1624, 1609, 1468, 1452, 1371, 1254, 1203, 1156, 1088, 1014 cm-¹. MS (EI+): m/z (%) = 247 (100) [M+ ], 232 (26). HRMS (EI+): m/z calcd for C17H13NO: 247.0997; found: 247.0987 [M+ ] (4.0 ppm error). Anal. Calcd for C17H13NO: C, 82.57; H, 5.30; N, 5.66. Found: C, 82.39; H, 5.36; N, 5.57.
4,6-Dichloro-3-phenylindole (11) Orange oil; R f  = 0.16 (PE-Et2O, 4:1). ¹H NMR (400 MHz, CDCl3): δ = 8.30 (br s, 1 H), 7.50 (dd, J = 8.0, 1.5 Hz, 2 H), 7.42-7.36 (m, 3 H), 7.34 (d, J = 2.0 Hz, 1 H), 7.19 (d, J = 2.5 Hz, 1 H), 7.15 (d, J = 2.0 Hz, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 137.5, 134.5, 131.0, 128.1, 127.6, 127.2, 126.9, 124.9, 122.3, 121.9, 119.5, 110.1. IR (neat): νmax = 3417, 3079, 2921, 2851, 1601, 1546, 1474, 1423, 1393, 1188, 1129, 1105, 1076 cm-¹. MS (EI+): m/z (%) = 263 (64) [³7Cl³5ClM+ ], 261 (100) [³5Cl³5ClM+ ], 199 (25). HRMS (EI+): m/z calcd for C14H9NCl2: 261.0112; found: 261.0108 [M+ ] (1.5 ppm error)].