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Synlett 2009(11): 1822-1826  
DOI: 10.1055/s-0029-1217357
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Carbazoles and 1,2-Dihydrocarbazoles by Domino ‘Twofold Heck-6π-Electrocyclization’ Reactions of Di- and Tribromo-N-methylindoles

Munawar Hussaina, Đãng Thanh Tùnga, Peter Langer*a,b
a Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany
b Leibniz-Institut für Katalyse an der Universität Rostock e.V., Albert Einstein Str. 29a, 18059 Rostock, Germany
Fax: +49(381)4986412; e-Mail: peter.langer@uni-rostock.de;
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Publication History

Received 19 February 2009
Publication Date:
12 June 2009 (online)

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Abstract

The palladium(0)-catalyzed Heck cross-coupling reaction of 2,3-dibromo- and 2,3,6-tribromo-N-methylindole, using Pd(OAc)2 as the catalyst and a novel biaryl monophosphine ligand developed by Buchwald and co-workers, afforded the corresponding di- and trialkenylindoles in high yields. The formation of 1,2-­dihydrocarbazoles by a domino ‘twofold Heck-6π-electrocyclization’ was observed when the reaction was carried out at 120 ˚C rather than 90 ˚C.

Key Words

cross-coupling - electrocyclic reactions - nitrogen heterocycles - Heck reaction - palladium

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Synthesis of 2,3-Dibromo- N -methylindole (2a) To a THF solution (20 mL) of N-methylindole (1, 1.0 mL, 8.0 mmol) was added portionwise NBS (3.30 g, 18.4 mmol) at -78 ˚C, and the soln was stirred at this temperature for 4 h. To the soln was added water (25 mL). The organic and the aqueous layer were separated and the latter was extracted with CH2Cl2 (3 × 25 mL). The combined organic layers were washed with a saturated aqueous soln of NaHCO3, dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by flash silica column chromatography (pure heptanes) to yield 2a as a colorless solid (1.83 g, 90%).

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General procedure for Heck cross-coupling reactions. In a pressure tube (glass bomb) a suspension of Pd(OAc)2 (12 mg, 0.05 mmol, 1.25 mol% per Br) and dicyclohexyl (2",6"-dimethoxybiphenyl-2-yl) phosphine (L) (41 mg, 0.10 mmol) in DMF (5 mL) was purged with argon and stirred at 20 ˚C to get a yellowish or brownish transparent soln. To the stirred soln were added the brominated indole 2a,b (1.0 mmol), Et3N (1.1 mL, 8.0 mmol) and the acrylate (1.25 equiv. per Br). The reaction mixture was stirred at 120 ˚C for 48 h. The soln was cooled to 20 ˚C, poured into H2O, and CH2Cl2 (25 mL each), and the organic and the aqueous layer were separated. The latter was extracted with CH2Cl2 (3 × 25 mL). The combined organic layers were washed with H2O (3 × 20 mL), dried (Na2SO4), and concentrated in vacuo. The residue was purified by chromatography (flash silica gel, heptanes-EtOAc).
Diethyl 9-Methyl-2,9-dihydro-1 H -carbazole-2,3-dicarboxylate (5b) Product 5b was prepared starting with 2a (367 mg, 1.0 mmol) as a yellow solid (297 mg, 93%), mp 100-103 ˚C. ¹H NMR (250 MHz, CDCl3): δ = 1.10 (s, 3 H, CH3), 1.30 (s, 3 H,CH3), 2.90 (dd, 1 Hα, J = 8.8, 17.1 Hz, H-1), 3.50 (dd, 1 Hβ, J = 2.6, 17.2 Hz, H-1), 3.60 (s, 3 H, NCH3), 3.90-4.10 (m, 3 H, Hα and CH2O), 4.20 (q, J = 7.1, 13.5 Hz, 2 H, CH2O), 7.10-7.20 (m, 3 H, ArH), 7.50-7.60 (m, 1 H, ArH), 7.90 (s, 1 H, H-4). ¹³C NMR (75 MHz, CDCl3): δ = 13.0 (CH3), 13.5 (CH3), 22.8 (CH2), 28.7 (CH, C-4), 37.7 (NCH3), 59.3 (CH2O), 60.1 (CH2O), 108.3 (C), 108.6 (CH), 115.4 (C), 116.9, 120.0, 120.8 (CH), 124.1(C), 131.2 (CH), 137.0, 138.6 (C), 166.3, 172.3 (CO). IR (KBr): ν = 2981, 2928, 2854(w), 1725(s), 1629, 1599(w), 1470 1454(m), 1372, 1261, 1238(s), 1109, 1079, 147(m), 787, 747, 723, 608, 561(w)cm-¹. GC-MS (EI, 70 eV): m/z (%) = 325(89) [M - 2]+(carbazole), 280(13), 252(100), 208(07), 179(13). HRMS (ESI+): m/z calcd for C19H19NO4 [M - 2]+(carbazole): 325.13141; found: 325.13161.

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Dibutyl 9-Methyl-9 H -carbazole-2,3-dicarboxylate (6)
To xylene (5 mL) were added 5c (100 mg, 0.26 mmol) and Pd/C (10 mg, 10 mol%). The soln was stirred under reflux for 48 h under argon atmosphere. The reaction mixture was filtered, and the filtrate was concentrated in vacuo to give 6 as a light yellow solid (99 mg, 100%). ¹H NMR (250 MHz, CDCl3): δ = 0.90 (t, 3 H, J = 7.4 Hz, CH3), 0.90 (t, 3 H, J = 7.3 Hz, CH3), 1.30-1.50 (m, 4 H, 2 CH2), 1.60-1.80 (m, 4 H, 2 CH2), 3.80 (s, 3 H, NCH3), 4.30 (t, 2 H, J = 6.8 Hz, CH2O), 4.30 (t, 2 H, J = 6.7 Hz, CH2O), 7.20-7.30 (m, 1 H, ArH), 7.30-7.40 (m, 1 H, ArH), 7.40-7.50 (m, 1 H, ArH), 7.60 (s, 1 H, H-1), 8.00-8.10 (m, 1 H, ArH), 8.40 (s, 1 H,
H-4). ¹³C NMR (62 MHz, CDCl3): δ = 13.7, 13.8 (CH3), 19.2, 19.3 (CH2), 29.4 (NCH3), 30.6, 30.8 (CH2), 65.3, 65.7 (CH2O), 109.0, 109.1, 120.2, 121.0 (CH), 121.7, 122.2 (C), 122.4 (CH), 123.6 (C), 127.1 (CH), 131.1, 141.5, 142,1 (C), 167.9, 169.4 (CO). IR (KBr): ν = 2956, 2931, 2871(w), 1709(s), 1464, 1387, 1362, 1340, 1325(m)1255, 1221(s), 1131, 1106, 1077, 1045(m), 950, 902, 843, 829(w), 784, 743, 721(m), 632, 608, 561(w)cm-¹. GC-MS (EI, 70 eV):
m/z (%) = 381(56) [M+], 308(15), 280(100), 224(87), 212(27), 206(77), 180(10), 152(11). HRMS (EI, 70 eV):
m/z calcd for C23H27NO4 [M+]: 381.19401; found: 381.19422.