Gold-Facilitated ‘6-Exo-dig’ Intramolecular
Cyclization of 2-[(2-Nitrophenyl)ethynyl]phenylacetic
Acids: General Access to 5H-Benzo[b]carbazole-6,11-diones

Cristian O. Salas; Francisco J. Reboredo; Juan C. Estévez; Ricardo A. Tapia; Ramón J. Estévez

doi:10.1055/s-0029-1218362

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Synlett 2009(19): 3107-3110
DOI: 10.1055/s-0029-1218362

LETTER

Gold-Facilitated ‘6-Exo-dig’ Intramolecular Cyclization of 2-[(2-Nitrophenyl)ethynyl]phenylacetic Acids: General Access to 5H-Benzo[b]carbazole-6,11-diones

Cristian O. Salas^a, Francisco J. Reboredo^b, Juan C. Estévez^b, Ricardo A. Tapia^a, Ramón J. Estévez*^b
^a Departamento de Química Orgánica, Facultad de Química, Pontifícia Universidad Católica de Chile, 782043 Santiago, Chile
^b Departamento de Química Orgánica, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
Fax: +34(981)591014; e-Mail: ramon.estevez@usc.es;

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Publication History

Received 13 August 2009
Publication Date:
13 November 2009 (online)

Abstract
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Abstract

The preliminary results of a regiospecific synthesis of (Z)-1-(2-nitrobenzylidene)isochroman-3-ones by gold(I)-catalyzed cycloisomerization of phenylethynylacetic acids under mild conditions is described. These novel lactones proved to be suitable starting materials for a new, general access to 5H-benzo[b]carbazole-6,11-diones.

Key words

alkynes - annulations - fused-ring systems - gold(I) chloride - indoles - lactones - nitro compounds - quinones

References and Notes

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9

All new compounds gave satisfactory analytical and spectroscopic data. Selected physical and spectroscopic data follow. Compound 6a: oil; IR (NaCl): 3282 (CºCH), 2106 (CºC), 1736 (C=O) cm^-¹; ^¹H NMR (CDCl₃): δ = 3.29 (s, 1 H, CH), 3.52 (s, 2 H, CH₂), 3.66 (s, 3 H, OCH₃), 3.85 (s, 3 H, OCH₃), 6.82 (d, J = 8.5 Hz, 1 H, ArH), 7.21 (dd, J = 8.5 Hz, 1 H, ArH), 7.35 (d, J = 2.0 Hz, 1 H, ArH); ^¹³C NMR (CDCl₃): δ = 39.8 (CH₂), 52.0 (OCH₃), 55.8 (OCH₃), 80.0 (CH), 81.2 (C), 110.6 (ArH), 111.1 (Ar), 125.9 (Ar), 131.0 (ArH), 134.7 (ArH), 159.6 (Ar), 171.8 (C=O); MS: m/z (%) = 205 (100) [M + 1]⁺. Compound 6b: mp 81-83 ˚C (CH₂Cl₂-MeOH); IR (NaCl): 3250 (CºCH), 2070 (CºC), 1722 (C=O) cm^-¹; ^¹H NMR (CDCl₃): δ = 3.24 (s, 1 H, CH), 3.69 (s, 3 H, OCH₃), 3.79 (s, 2 H, CH₂), 3.85 (s, 3 H, OCH₃), 3.87 (s, 3 H, OCH₃), 6.79 (s, 1 H, ArH), 6.98 (s, 1 H, ArH); ^¹³C NMR (CDCl₃): d = 38.4 (CH₂), 51.3 (OCH₃), 55.2 (OCH₃), 55.3 (OCH₃), 79.8 (CH), 81.3 (C), 112.1 (ArH), 113.6 (Ar), 114.3 (ArH), 129.4 (Ar), 147.1 (Ar), 149.1 (Ar), 171.0 (C=O); MS: m/z (%) = 235 (100) [M + 1]⁺. Compound 7a: mp 87-88 ˚C (CH₂Cl₂-MeOH); IR (NaCl): 2205 (CºC), 1725 (C=O), 1565 (NO₂), 1344 (NO₂) cm^-¹; ^¹H NMR (CDCl₃): δ = 3.70 (s, 3 H, OCH₃), 3.83 (s, 3 H, OCH₃), 3.94 (s, 2 H, CH₂), 6.83 (d, J = 8.5 Hz, 1 H, ArH), 6.86 (s, 1 H, ArH), 7.43 (t, J = 8.5 Hz, 1 H, ArH), 7.546 (m, 2 H, 2 × ArH), 7.70 (d, J = 9.1 Hz, 1 H, ArH), 8.08 (d, J = 8.2 Hz, 1 H, ArH); ^¹³C NMR (CDCl₃): δ = 40.2 (CH₂), 52.6 (OCH₃), 55.8 (OCH₃), 87.7 (C), 96.1 (C), 113.5 (ArH), 115.3 (Ar), 116.1 (ArH), 119.6 (Ar), 125.2 (ArH), 128.6 (ArH), 133.3 (ArH), 134.8 (ArH), 134.9 (Ar), 139.1 (Ar), 160.9 (Ar), 171.9 (C=O); MS: m/z (%) = 326 (53) [M + 1]⁺, 207 (100). Compound 7b: mp 142-145 ˚C (CH₂Cl₂-MeOH); IR (NaCl): 2201 (CºC), 1724 (C=O), 1565 (NO₂), 1337 (NO₂) cm^-¹; ^¹H NMR (CDCl₃): δ = 3.71 (s, 2 H, CH₂), 3.92 (s, 6 H, 2 × OCH₃), 3.94 (s, 3 H, OCH₃), 6.84 (s, 1 H, ArH), 7.08 (s, 1 H, ArH), 7.46 (t, J = 7.3 Hz, 1 H, ArH), 7.60 (t, J = 7.3 Hz, 1 H, ArH), 7.73 (d, J = 7.3 Hz, 1 H, ArH), 8.09 (d, J = 7.3 Hz, 1 H, ArH); ^¹³C NMR (CDCl₃): δ = 39.2 (CH₂), 52.1 (OCH₃), 55.9 (OCH₃), 56.0 (OCH₃), 87.7 (C), 95.7 (C), 112.6 (ArH), 114.6 (ArH), 118.9 (Ar), 124.7 (ArH), 128.2 (ArH), 130.5 (Ar), 132.8 (ArH), 134.4 (ArH), 147.8 (Ar), 148.8 (Ar), 150.2 (Ar), 171.7 (Ar), 179.2 (C=O); MS: m/z (%) = 356 (0.6) [M + 1]⁺, 17 (100). Compound 1a: mp 152-154 ˚C (CH₂Cl₂); IR (NaCl): 2204 (CºC), 1703 (C=O), 1564 (NO₂), 1337 (NO₂) cm^-¹; ^¹H NMR (acetone-d ₆): δ = 3.85 (s, 3 H, OCH₃), 3.97 (s, 2 H, CH₂), 6.93 (dd, J = 8.8, 2.5 Hz, 1 H, ArH), 7.03 (d, J = 2.5 Hz, 1 H, ArH), 7.48 (t, J = 7.3 Hz, 1 H, ArH), 7.63 (t, J = 7.3 Hz, 1 H, ArH), 7.77 (m, 2 H, ArH), 8.10 (d, J = 7.3 Hz, 1 H, ArH); ^¹³C NMR (acetone-d ₆): δ = 41.0 (CH₂), 56.8 (OCH₃), 89.3 (C), 97.3 (C), 114.6 (ArH), 116.6 (Ar), 118.0 (ArH), 120.3 (Ar), 126.5 (ArH), 130.7 (ArH), 134.0 (Ar), 135.1 (ArH), 135.8 (ArH), 136.3 (ArH), 141.5 (Ar), 162.6 (Ar), 173.1 (C=O); MS: m/z (%) = 312 (22) [M + 1]⁺, 282 (100). Compound 1b: mp 163-165 ˚C (CH₂Cl₂); IR (NaCl): 2204 (CºC), 1710 (C=O), 1566 (NO₂), 1337 (NO₂) cm^-¹; ^¹H NMR (CDCl₃): δ = 3.92 (s, 2 H, CH₂), 3.92 (s, 6 H, 2 × OCH₃), 6.89 (s, 1 H, ArH), 7.10 (s, 1 H, ArH), 7.48 (t, J = 7.3 Hz, 1 H, ArH), 7.63 (t, J = 7.3 Hz, 1 H, ArH), 7.77 (d, J = 7.3 Hz, 1 H, ArH), 8.10 (d, J = 7.3 Hz, 1 H, ArH); ^¹³C NMR (CDCl₃/DMSO-d ₆): δ = 39.9 (CH₂), 55.4 (OCH₃), 55.5 (OCH₃), 87.4 (C), 95.4 (C), 112.5 (ArH), 114.3 (Ar), 114.3 (ArH), 118.6 (Ar), 124.3 (ArH), 128.0 (ArH), 130.8 (Ar), 132.7 (ArH), 134.2 (ArH), 147.4 (Ar), 148.4 (Ar), 149.8 (Ar), 173.6 (C=O); MS: m/z (%) = 342 (0.6) [M + 1]⁺, 33 (100). Compound 2a: mp 141-142 ˚C (CH₂Cl₂); IR (NaCl): 1764 (C=O), 1514 (NO₂), 1307 (NO₂) cm^-¹; ^¹H NMR (CDCl₃): δ = 3.85 (s, 2 H, CH₂), 3.87 (s, 3 H, OCH₃), 6.68 (s, 2 H, ArH and CH), 6.91 (dd, J = 8.8 Hz, 1 H, ArH), 7.39 (t, J = 8.5 Hz, 1 H, ArH), 7.61 (m, 2 H, 2 × ArH), 7.97 (dd, J = 8.2 Hz, 1 H, ArH), 8.04 (dd, J = 8.0 Hz, 1 H, ArH); ^¹³C NMR (CDCl₃): δ = 35.0 (CH₂), 55.5 (OCH₃), 101.1 (CH), 111.8 (ArH), 114.7 (ArH), 120.0 (Ar), 124.6 (ArH), 126.6 (ArH), 127.7 (ArH), 128.5 (Ar), 130.5 (Ar), 132.1 (ArH), 132.8 (ArH), 148.1 (Ar), 148.6 (Ar), 161.6 (Ar), 165.0 (C=O); MS: m/z (%) = 312 (50) [M + 1]⁺, 282 (100). Compound 2b: mp 163-165 ˚C (CH₂Cl₂); IR (NaCl): 1736 (C=O), 1518 (NO₂), 1292 (NO₂) cm^-¹; ^¹H NMR (CDCl₃): δ = 3.85 (s, 2 H, CH₂), 3.93 (s, 3 H, OCH₃), 3.96 (s, 3 H, OCH₃), 6.63 (s, 1 H, CH), 6.68 (s, 1 H, ArH) 7.09 (s, 1 H, ArH), 7.40 (t, J = 7.2 Hz, 1 H, ArH), 7.63 (t, J = 7.9 Hz, 1 H, ArH), 8.00 (d, J = 8.2 Hz, 1 H, ArH), 8.06 (d, J = 8.2 Hz, 1 H, ArH); ^¹³C NMR (CDCl₃/DMSO-d ₆): δ = 34.2 (CH₂), 56.1 (2 × OCH₃), 101.2 (CH), 106.9 (ArH), 109.4 (ArH), 112.6 (Ar), 119.5 (Ar), 121.8 (Ar), 124.7 (ArH), 127.7 (ArH), 128.5 (Ar), 132.2 (ArH), 132.9 (ArH), 148.7 (Ar), 149.0 (Ar), 151.3 (Ar), 165.0 (C=O); MS: m/z (%) = 342 (0.6) [M + 1]⁺, 33 (100). Compound 9a: mp 205-206 ˚C (MeOH); IR (NaCl): 3331 (OH), 1675 (C=O), 1637 (C=O), 1525 (NO₂), 1356 (NO₂) cm^-¹; ^¹H NMR (DMSO-d ₆): δ = 4.03 (s, 3 H, OCH₃), 7.41 (dd, J = 8.7 Hz, 1 H, ArH), 7.62-7.74 (m, 3 H, ArH), 7.80 (m, 1 H, ArH), 8.09 (d, J = 8.7 Hz, 1 H, ArH), 8.19 (d, J = 8.3 Hz, 1 H, ArH); ^¹³C NMR (DMSO-d ₆): δ = 57.0 (OCH₃), 109.2 (ArH), 113.8 (Ar), 115.1 (Ar), 119.8 (ArH), 123.3 (ArH), 126.8 (Ar), 127.9 (ArH), 131.7 (ArH), 134.0 (ArH), 136.0 (ArH), 147.5 (Ar), 149.4 (Ar), 161.8 (Ar), 176.3 (Ar), 178.9 (C=O), 184.1 (C=O); MS: m/z (%) = 326 (100) [M + 1]⁺. Compound 9b: mp 266-268 ˚C (MeOH); IR (NaCl): 3349 (OH), 1642 (C=O), 1525 (NO₂), 1337 (NO₂) cm^-¹; ^¹H NMR (CDCl₃):
δ = 4.03 (s, 3 H, OCH₃), 4.05 (s, 3 H, OCH₃), 7.52-7.58 (m, 5 H, ArH + OH), 7.66 (m, 1 H, ArH), 8.17 (dd, J = 8.2 Hz, 1 H, ArH); ^¹³C NMR (CDCl₃): δ = 57.0 (OCH₃), 57.1 (OCH₃), 108.2 (ArH), 109.6 (ArH), 119.6 (Ar), 123.9 (Ar), 125.0 (ArH), 126.2 (Ar), 128.3 (Ar), 129.9 (ArH), 133.0 (ArH), 133.4 (ArH), 149.5 (Ar), 152.0 (Ar), 153.4 (Ar), 155.2 (Ar), 180.8 (C=O), 182.6 (C=O); MS: m/z (%) = 356 (29) [M + 1]⁺, 309 (100).

10

PdCl₂(PPh₃)₂ (0.22 mmol) was added under argon to a degassed mixture of CuI (0.22 mmol) and o-iodophenyl-acetic acid ester 5a or 5b (3.6 mmol) in anhydrous THF (20 mL). After 5 min stirring, Et₃N (5 mL) was first added, then TMS-acetylene (3.60 mmol) was slowly added and the resulting mixture was stirred at room temperature for 1.5 h for 6a or 12 h for 6b. The solids were filtered off through a Celite pad, the solvents were removed in vacuo, and the crude oil was poured into water and extracted with methylene chloride. The pooled organic liquids were washed with brine, dried over anhydrous sodium sulfate and concentrated to dryness in vacuo. Compound 6a or 6b were isolated by flash column chromatography.

11

PdCl₂(PPh₃)₂ (0.16 mmol) was added under argon to a degassed mixture of CuI (0.16 mmol) and o-bromonitro-benzene (2.8 mmol) in anhydrous THF (20 mL). After 5 min stirring, Et₃N (5 mL) was first added, then a solution of 6a or 6b (3.85 mmol) in anhydrous THF (10 mL) was slowly added and the resulting mixture was stirred at room temperature for 12 h. The solids were filtered off through a Celite pad, the solvents were removed in vacuo and the filtrate was concentrated to dryness in vacuo. Compound 7a or 7b were isolated by flash column chromatography.

12

In a flask containing 1a or 1b (1.00 equiv) and K₂CO₃ (0.10 equiv), acetonitrile (2 mL/0.4 mmol) was added under argon. The solution was purged with argon three times and then AuCl (0.10 equiv) was added. After stirring at room temperature for 12 h, the reaction mixture was filtered through a Celite pad and liquids from the filtrate were removed under reduced pressure. Flash column chroma-
tography of the crude material allowed compound 2a or 2b to be isolated.