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Synlett 2006(2): 318-320  
DOI: 10.1055/s-2005-923605
LETTER
© Georg Thieme Verlag Stuttgart · New York

An Example of Regioselective Fischer Indole Annulation

Jens Christoffers*
Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany
Fax: +49(711)6854269; e-Mail: jchr@oc.uni-stuttgart.de;
Further Information

Publication History

Received 27 October 2005
Publication Date:
23 December 2005 (online)

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Abstract

Bicyclo[n.4.0]alkan-3-ones (n = 3, 4, 5) with a trans bridge-head configuration give linear annulated tetrahydro­carbazole derivatives in Fischer indole synthesis. The structure of two tetrahydro­carbazoles was confirmed by X-ray crystal analysis. The hexa­hydroindanone derivative with a cis bridge-head configuration gives, contrastingly, the angular annulation product under the same reaction conditions.

Key words

carbazole derivatives - indole derivatives - heterocycles - regioselectivity - annulation

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Ethyl 6,6a,7,8,9,10-Hexahydro-5 H -cyclopenta[ b ]carb-azole-9a-carboxylate ( 2a); Typical Procedure A mixture of ketone 1a (191 mg, 0.908 mmol), glacial AcOH (2.3 mL), TFA (0.80 mL), and PhNHNH2 (260 mg, 2.40 mmol) was stirred for 16 h at 100 °C in a tightly closed reaction vial. The mixture was added to ice-H2O (ca. 20 g) and the resulting emulsion was extracted with CH2Cl2 (3 × 10 mL). The combined organic layers were dried (MgSO4) and the solvent was evaporated. The residue was chromatographed twice (SiO2; hexanes-EtOAc, 5:1, R f 0.36) to furnish carbazole derivative 2a (210 mg, 0.881 mmol, 97%) as light yellow crystals, mp 175-177 °C. 1H NMR (500 MHz, CDCl3): δ = 1.07 (t, J = 7.1 Hz, 3 H), 1.68-1.74 (m, 1 H), 1.83-1.90 (m, 2 H), 1.93-2.00 (m, 2 H), 2.17-2.23 (m, 2 H), 2.51 (dt, J = 15.1, 2.0 Hz, 1 H), 2.85 (ddd, J = 15.7, 5.7, 1.2 Hz, 1 H), 3.09 (br t, J = 13.7 Hz, 1 H), 3.59 (d, J = 15.0 Hz, 1 H), 3.88-3.93 (m, 1 H), 3.95-4.03 (m, 1 H), 7.06 (td, J = 7.4, 1.1 Hz, 1 H), 7.10 (td, J = 7.4, 1.2 Hz, 1 H), 7.25 (dd, J = 6.0, 1.1 Hz, 1 H), 7.46 (br d, J = 7.5 Hz, 1 H), 7.70 (br s, 1 H, NH). 13C{1H} NMR (75 MHz, CDCl3): δ = 175.59 (C), 136.40 (C), 134.88 (C), 127.50 (C), 120.95 (CH), 118.99 (CH), 117.72 (CH), 110.37 (CH), 110.02 (C), 59.84 (CH2), 53.72 (C), 46.11 (CH), 36.73 (CH2), 31.90 (CH2), 28.01 (CH2), 26.06 (CH2), 22.59 (CH2), 14.02 (CH3). MS (EI, 70 eV), m/z (%) = 283 (100) [M+]. Anal. calcd for C18H21NO2 (283.37): C, 76.30; H, 7.47; N, 4.94. Found: C, 76.09; H, 7.53; N, 4.83.

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CCDC-286970 (2c) and CCDC-286971 (2a) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge at www.ccdc.cam.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Center, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 (1223)336033; E-mail: deposit@ccdc.cam.ac.uk].

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Ethyl 2,3,4,5,6,10c-Hexahydro-1 H -cyclopenta[ c ]carb-azole-3a-carboxylate ( 4) Yellow oil; R f 0.30 (SiO2; hexanes-EtOAc, 5:1). 1H NMR (500 MHz, CDCl3): δ = 7.67 (br s, 1 H, NH), 7.50 (br d, J = 7.5 Hz, 1 H), 7.26 (br d, J = 7.5 Hz, 1 H), 7.10 (td, J = 7.1, 1.1 Hz, 1 H), 7.07 (td, J = 7.2, 1.1 Hz, 1 H), 4.11-4.19 (m, 1 H), 4.04-4.11 (m, 1 H), 3.76 (t, J = 8.3 Hz, 1 H), 2.78-2.88 (m, 1 H), 2.67 (dt, J = 16.4, 4.9 Hz, 1 H), 2.39-2.46 (m, 1 H), 2.29 (dt, J = 13.2, 4.8 Hz, 1 H), 2.17 (ddd, J = 12.6, 8.8, 6.0 Hz, 1 H), 1.86-1.96 (m, 1 H), 1.77-1.86 (m, 2 H), 1.61-1.77 (m, 2 H), 1.22 (t, J = 7.1 Hz, 3 H). 13C{1H} NMR (75 MHz, CDCl3): δ = 177.66 (C), 136.02 (C), 132.69 (C), 127.47 (C), 120.91 (CH), 118.92 (CH), 118.22 (CH), 112.16 (C), 110.53 (CH), 60.52 (CH2), 52.26 (C), 40.17 (CH), 36.86 (CH2), 33.04 (CH2), 29.45 (CH2), 24.82 (CH2), 20.75 (CH2), 14.15 (CH3). HRMS (EI, 70 eV): m/z calcd for C18H21NO2 [M+], 283.1572; found: 283.1574