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Synlett 2004(2): 0267-0270  
DOI: 10.1055/s-2004-815397
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Novel Total Synthesis of Indolo[2,3-b]naphthalene-6,11-diones

Marcos Fernandez, Carlos Barcia, Juan C. Estévez, Ramón J. Estévez*, Luis Castedo
Departamento de Química Orgánica and Unidade Asociada (C.S.I.C.), Universidade de Santiago, 15782 Santiago de Compostela, Spain
Fax: +34(981)591014; e-Mail: qorjec@usc.es;
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Publication History

Received 13 October 2003
Publication Date:
12 January 2004 (online)

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Abstract

A new total synthesis of indolo[2,3-b]naphthalene-6,11-diones is described, which involves a novel opening of 2-(2′-nitrophenyl)-2-methoxycarbonyl-1-indanones to 2-[2-methoxycarbonyl-2-(2-nitrophenyl)ethyl]benzoic acids followed by a two-steps transformation of the latter into 2-(1H-indol-3-ylmethyl)benzoic acid methyl esters, which are then converted into the target compounds in three steps.

Key words

indoles - carbazoles - quinones

11

All new compounds gave satisfactory analytical and spectroscopic data. Selected physical and spectroscopic data are as follows. Compound 3a: Mp 135-137 ºC (MeOH). 1H NMR (CDCl3): δ = 1.16 (t, J = 7.0 Hz, 3 H, CH3), 3.37 (d,
J = 18.0 Hz, 1 H, CHH), 4.12-4.17 (m, 2 H, CH2O), 4.57 (d, J = 18.0 Hz, 1 H, CHH), 7.23-7.25 (m, 1 H, ArH), 7.44-7.54 (m, 4 H, 4 × ArH), 7.68-7.71 (m, 1 H, ArH), 7.90 (d, J = 8.0 Hz, 1 H, ArH), 8.09 (dd, J = 8.1 Hz and J′ = 1.5 Hz, 1 H, ArH). 13C NMR (CDCl3): δ = 13.8 (CH3), 42.5 (CH2), 62.6 (CH2), 65.6 (C), 125.1 (CH), 125.8 (CH), 126.6 (CH), 128.1 (CH), 128.5 (CH), 129.6 (CH), 133.6 (CH), 135.0 (C), 135.6 (C), 136.4 (CH), 148.8 (C), 153.7 (C), 168.1 (C=O), 201.2 (C=O). MS (CI): m/z (%) = 326(1) [M+ + 1], 47(100). Compound 4a: Oil. 1H NMR (CDCl3): 3.42-3.49 (m, 1 H, CHH), 3.64 (s, 3 H, CO2Me), 3.93-4.00 (m, 1 H, CHH), 4.72 (t, J = 8.0 Hz, 1 H, CH), 6.96 (d, J = 9.0 Hz, 1 H, ArH), 7.21-7.30 (m, 2 H, 2 × ArH), 7.34-7.53 (m, 3 H, 3 × ArH), 7.81-7.91 (m, 2 H, 2 × ArH). 13C NMR (CDCl3): δ = 37.4 (CH2), 47.8 (CH), 52.1 (OMe), 52.3 (OMe), 124.6 (CH), 126.7 (CH), 127.9 (CH), 129.5 (C), 130.8 (CH), 130.9 (CH), 131.6 (CH), 131.7 (CH), 132.7 (CH), 133.2 (C), 139.8 (C), 149.1 (C), 167.4 (C=O), 172.4 (C=O). MS (FAB): m/z (%) = 344(22) [M+ + 1], 149(100). Compound 5a: Mp 110-112 ºC (MeOH). 1H NMR (CDCl3): δ = 3.22-3.32 (m, 1 H, CHH), 3.83-3.91 (m, 5 H, CHH, CH, CO2Me), 6.66 (d, J = 7.5 Hz, 1 H, ArH), 6.84-6.89 (m, 2 H, 2 × ArH), 7.13-7.19 (m, 1 H, ArH), 7.29-7.49 (m, 3 H, 3 × ArH), 7.99 (m, 1 H, ArH), 8.81 (br s, 1 H, NH). 13C NMR (CDCl3): δ = 35.6 (CH2), 46.8 (CH), 52.1 (OMe), 109.6 (CH), 121.7 (CH), 124.9 (CH), 126.8 (CH), 127.7 (CH), 129.1 (C), 129.8 (C), 131.0 (CH), 131.7 (CH), 132.5 (CH), 139.9 (C), 141.3 (C), 167.6 (C=O), 179.6 (C=O). MS: m/z (%) = 281(13) [M + ], 220(100). Compound 6a: Mp 111-113 ºC (MeOH). 1H NMR (CDCl3): δ = 3.95 (s, 3 H, CO2Me), 4.49 (d, J = 10 Hz, 2 H, CH2), 6.99-7.42 (m, 6 H, 6 × ArH), 7.92 (d, J = 7.5 Hz, 1 H, ArH), 8.16 (s, 1 H, ArH). 13C NMR (CDCl3): δ = 28.7 (CH2), 52.2 (OMe), 109.4 (C), 110.3 (CH), 113.2 (C), 113.7 (C), 118.7 (CH), 120.0 (CH), 122.2 (CH), 125.8 (CH), 127.8 (C), 129.5 (CH), 130.3 (CH), 131.8 (CH), 136.1 (C), 141.1 (C), 168.3 (C=O). MS (CI): m/z (%) = 345(18) [M+ + 2], 343(22) [M+], 264(100). Compound 6b: Mp 56-58 ºC (MeOH). 1H NMR (CDCl3): δ = 3.87 (s, 3 H, CO2Me), 4.54 (s, 2 H, CH2), 6.82 (s, 1 H, CH), 7.10-7.41 (m, 5 H, 5 × ArH), 7.58 (d, J = 8.0 Hz, 1 H, ArH), 7.91-7.99 (m, 2 H, 2 × ArH). 13C NMR (CDCl3): δ = 29.5 (CH2), 51.9 (OMe), 110.9 (CH), 115.2 (C), 118.9 (CH), 119.1 (CH), 121.8 (CH), 122.5 (CH), 125.8 (CH), 127.4 (C), 129.8 (C), 130.2 (CH), 130.7 (CH), 131.7 (CH), 136.2 (C), 142.3 (C), 168.4 (C=O). MS: m/z (%) = 265(66) [M+], 204(100). Compound 7a: Mp 206-208 ºC (MeOH). 1H NMR (CDCl3-acetone-DMSO): δ = 3.77 (s, 3 H, OMe), 6.61 (d, J = 5.0 Hz, 1 H, CH), 6.84 (m, 2 H, 2 × ArH), 7.04 (d, J = 5.0 Hz, 1 H, ArH), 7.47-7.59 (m, 3 H, 3 × ArH), 8.05 (s, 2 H, 2 × ArH), 9.35 (br s, 1 H, NH). 13C NMR (CDCl3-acetone-DMSO): δ = 51.4 (OMe), 109.3 (CH), 120.4 (CH), 120.9 (C), 122.0 (CH), 126.7 (C), 128.3 (C), 128.4 (CH), 128.8 (CH), 129.1 (CH), 130.3 (CH), 131.7 (CH), 136.2 (CH), 136.2 (C), 141.8 (C), 165.5 (C=O), 168.3 (C=O). MS: m/z (%) = 279(1) [M+], 58(100). Compound 8b: Mp 378-380 °C (MeOH). 1H NMR (DMSO): δ = 7.25-7.35 (m, 2 H, 2 × Ar-H), 7.55-7.57 (m, 2 H, 2 × Ar-H), 7.78-7.84 (m, 1 H, Ar-H), 7.95-8.07 (m, 3 H, 3 × Ar-H), 12.94 (br s, 1 H, NH). 13C NMR (TFAA): δ = 113.3 (CH), 121.0 (C), 123.5 (C), 125.1 (CH), 128.9 (CH), 130.2 (CH), 130.3 (CH), 130.4 (CH), 134.5 (CH), 135.1 (C), 136.2 (CH), 139.7 (C), 140.6 (C), 148.4 (C), 154.3 (C), 179.2 (2 × C=O). MS: m/z (%) = 247(44), 219(100). Compound 3b: Mp 151-153 ºC (MeOH). 1H NMR (CDCl3): δ = 1.18 (t, J = 7.0 Hz, 3 H, CH3), 3.30 (d, J = 18.5 Hz, 1 H, CHH), 3.91 (s, 3 H, OMe), 4.14 (q, J = 7.0 Hz, 2 H, CH2O), 4.51 (d, J = 18.0 Hz, 1 H, CHH), 6.91-6.99 (m, 2 H, 2 × ArH), 7.25 (s, 1 H, 2 × ArH), 7.41-7.54 (m, 2 H, 2 × ArH), 7.82 (d, J = 9.0 Hz, 1 H, ArH), 8.07 (d, J = 8.5 Hz, 1 H, ArH). 13C NMR (CDCl3): δ = 13.9 (CH3), 42.6 (CH2), 55.9 (CH3), 62.5 (CH2), 65.8 (C), 109.2 (CH), 116.5 (CH), 125.6 (CH), 126.7 (CH), 128.1 (C), 128.3 (CH), 129.6 (CH), 133.5 (CH), 135.7 (C), 148.7 (C), 156.8 (C), 166.5 (C), 168.2 (C=0), 198.6 (C=O). MS (CI): m/z
(%) = 356(1) [M+ + 1]; 266(100). Compound 4c: Mp 91-
93 ºC (MeOH). 1H NMR (CDCl3): δ = 3.37-3.43 (m, 1 H, CHH), 3.64 (s, 3 H, CO2Me), 3.68 (s, 3 H, CO2Me), 3.84
(s, 3 H, OMe), 3.96-4.01 (m, 1 H, CHH), 4.72 (t, J = 7.5 Hz, 1 H, CH), 6.41 (d, J = 3.0 Hz, 1 H, ArH), 6.72 (m, 1 H, ArH), 7.35-7.43 (m, 2 H, 2 × ArH), 7.49-7.51 (m, 1 H, ArH), 7.82 (d, J = 8.0 Hz, 1 H, ArH), 7.90 (d, J = 9.0 Hz, 1 H, ArH). 13C NMR (CDCl3): δ = 37.7 (CH2), 47.6 (CH3), 51.8 (CH3), 52.3 (CH3), 55.2 (CH), 112.2 (CH), 116.8 (CH), 121.5 (C), 124.7 (CH), 128.0 (CH), 131.0 (CH), 132.8 (CH), 133.3 (CH), 133.3 (C), 142.7 (C), 149.3 (C), 162.0 (C), 167.0 (C=O), 172.6 (C=O). MS (FAB): m/z (%) = 374(41) [M+ + 1], 154(100). Compound 5b: Mp 147-149 ºC (MeOH). 1H NMR (CDCl3): δ = 3.23-3.29 (m, 1 H, CHH), 3.79 (s, 3 H, OMe), 3.83 (s, 3 H, OMe), 3.85-3.89 (m, 2 H, CH, CHH), 6.70-6.90 (m, 5 H, 5 × ArH), 7.15 (t, J = 7.5 Hz, 1 H, ArH), 8.00 (d, J = 9.0 Hz, 1 H, ArH), 9.25 (s, 1 H, NH). 13C NMR (CDCl3): δ = 35.9 (CH2), 46.6 (CH), 51.7 (CH3), 55.3 (CH3), 109.7 (CH), 112.4 (CH), 117.6 (CH), 121.7 (CH), 121.8 (C), 124.9 (CH), 127.7 (CH), 129.2 (C), 133.4 (CH), 141.5 (C), 142.9 (C), 162.0 (C), 167.2 (C=O), 180.1 (C=O). MS: m/z (%) = 311(8) [M+], 279(100). Compound 6c: Mp 139-141 ºC (MeOH). 1H NMR (CDCl3): δ = 3.65 (s, 3 H, OMe), 3.93 (s, 3 H, OMe), 4.52 (d, J = 10.0 Hz, 2 H, CH2), 6.50-6.57 (m, 1 H, ArH), 6.71-6.75 (m, 1 H, ArH), 6.99-7.04 (m, 1 H, ArH), 7.12-7.16 (m, 1 H, ArH), 7.25-7.41 (m, 1 H, ArH), 7.99 (d, J = 9.0 Hz, 1 H, ArH), 8.21 (d, 1 H, ArH). 13C NMR (CDCl3): δ = 28.8 (CH2), 51.8 (CH3), 55.1 (CH3), 110.3 (CH), 110.4 (CH), 113.2 (C), 113.6 (C), 115.6 (CH), 118.7 (CH), 120.0 (CH), 121.5 (C), 122.2 (CH), 127.8 (C), 132.9 (CH), 136.1 (C), 144.3 (C), 162.3 (C), 167.7 (C=O). MS (FAB): m/z (%) = 376(3) [(M+ + 1) + 2], 374(5) [M+ + 1], 137(100). Compound 6d: Oil. 1H NMR (CDCl3): 3.73 (s, 3 H, OMe), 3.84 (s, 3 H, OMe), 4.54 (s, 2 H, CH2), 6.76-6.87 (m, 3 H, CH, 2 × ArH), 7.10 (t, J = 7.5 Hz, 1 H, ArH), 7.19 (t, J = 7.5 Hz, 1 H, ArH), 7.33 (d, J = 8.0 Hz, 1 H, ArH), 7.57 (d, J = 8.0 Hz, 1 H, ArH), 7.96-8.01 (m, 2 H, ArH, NH). 13C NMR (CDCl3): δ = 29.8 (CH2), 51.6 (OMe), 55.1 (OMe), 110.8 (CH), 111.0 (C), 115.2 (C), 116.4 (CH), 119.0 (CH), 119.2 (CH), 121.8 (C), 121.8 (CH), 122.6 (CH), 127.5 (C), 133.0 (CH), 136.3 (C), 145.6 (CH), 162.3 (C), 167.8 (C=O). MS: m/z (%) = 295(58) [M+], 220(100). Compound 7c: 206-208 ºC (MeOH). 1H NMR (CDCl3-acetone-DMSO): δ = 3.61 (s, 3 H, OMe), 3.64 (s, 3 H, OMe), 6.50-6.54 (m, 1 H, CH), 6.68-6.70 (m, 1 H, ArH), 6.79-6.84 (m, 2 H, ArH), 6.90-6.93 (m, 2 H, ArH), 7.89-7.95 (m, 2 H, ArH), 8.98 (br s, 1 H, NH). 13C NMR (CDCl3-acetone-DMSO): δ = 51.5 (CH3), 55.2 (CH3), 109.8 (CH), 114.1 (CH), 114.3 (CH), 121.0 (CH), 121.3 (C), 122.6 (CH), 126.8 (C), 129.2 (CH), 132.9 (CH), 137.2 (CH), 138.8 (C), 141.9 (C), 162.2 (C), 165.8 (C=O), 169.0 (C=O). MS: m/z (%) = 309 (12) [M+], 250(100). Compound 8d: Mp 386-388 °C (MeOH). 1H NMR (DMSO): δ = 3.87 (s, 3 H, OMe), 7.23-7.34 (m, 3 H, 3 × ArH), 7.43-7.54 (m, 1 H, ArH), 7.93-7.99 (m, 1 H, ArH), 8.53 (d, J = 8.6 Hz, 1 H, ArH), 12.8 (br s, 1 H, NH). 13C NMR (TFAA): δ = 54.8 (CH3), 111.3 (C), 112.7 (CH), 115.0 (C), 117.5 (CH), 119.6 (CH), 120.5 (C), 125.3 (CH), 129.9 (CH), 130.4 (CH), 130.6 (C), 132.2 (CH), 140.5 (C), 150.0 (C), 153.8 (C), 165.5 (C), 179.3 (2 × C=O). MS: m/z (%) = 277(42) [M+], 29(100).