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Synlett 2011(13): 1835-1840  
DOI: 10.1055/s-0030-1260965
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Palladium-Mediated Intramolecular C-O and C-C Coupling Reactions: An Efficient Synthesis of Benzannulated Oxazepino- and Pyranocarbazoles

Kumaresan Prabakarana, Matthias Zellerb, Karnam Jayarampillai Rajendra Prasad*a
a Department of Chemistry, Bharathiar University, Coimbatore 641046, India
Fax: +91(422)2422387; e-Mail: prasad_125@yahoo.com;
b Department of Chemistry, Youngstown State University, One University Plaza, Youngstown, OH 44555, USA
Further Information

Publication History

Received 21 March 2011
Publication Date:
21 July 2011 (online)

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Abstract

An efficient route towards the synthesis of benzannulated oxazepino- and pyranocarbazoles has been accomplished via palladium-catalyzed intramolecular C-O and C-C cross-coupling reactions, respectively.

Key words

C-O and C-C coupling - intramolecular arylation - palladium catalysis - oxazepinocarbazoles - pyranocarbazoles.

    References and Notes

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18

General Procedure for the Preparation of 4 and 5
To 2-halobenzoic acid (2.5 mmol) was added SOCl2 (2 mL). The solution was refluxed for 2 h, after which the excess of SOCl2 was removed under reduced pressure, and the residual traces were then removed by coevaporation with dry toluene. The acid chloride was then added to a solution of 1-hydroxy-carbazole (2.5 mmol) and Et3N (2 mL) in dry THF (10 mL) at 0 ˚C. After the addition of the acid chloride, the mixture was allowed to warm up to r.t. while stirring under a nitrogen atmosphere. After stirring overnight, the mixture was diluted with H2O and neutralized with 4% HCl to pH 7. The precipitated amide was then filtered off and washed with 4% HCl and copious amounts of H2O. The crude product was purified by chromatography using 1% EtOAc and afforded 4 and 5.
1-Hydroxy-9-(2-bromobenzoyl)-6-methylcarbazole (4a)
White solid; mp 126 ˚C; yield 0.682 g, 72%. IR (KBr): ν = 3432 (OH), 1646 (C=O) cm-¹. ¹H NMR (500 MHz, CDCl3): δ = 2.42 (s, 3 H, CH3), 6.86 (t, 1 H, J = 8.0 Hz, H-3), 7.13 (dd, 1 H, J m  = 2.0 Hz, J o  = 8.0 Hz, H-7), 7.21 (dd, 1 H, J m  = 2.0 Hz, J o  = 8.0 Hz, H-2), 7.58-7.62 (m, 2 H, Harom), 7.67-7.71 (m, 2 H, Harom), 7.75 (d, 1 H, J = 8.0 Hz, H-8), 7.85 (s, 1 H, H-5), 7.94 (dd, 1 H, J m  = 2.0 Hz, J o  = 7.5 Hz,
H-3′), 12.76 (s, 1 H, OH). ¹³C NMR (125 MHz, CDCl3): δ = 21.6 (CH3), 111.0, 111.6, 116.8, 119.1, 120.2, 122.3, 122.9, 126.1, 126.5, 127.5, 128.3, 129.9, 131.8, 132.2, 132.8, 138.4, 139.3, 148.5, 165.7 (CO). LC-MS: m/z = 380 [M + H+]. Anal. Calcd (%) for C20H14BrNO2: C, 63.32; H, 3.69; N, 3.69. Found: C, 63.34; H, 3.67; N, 3.72.

19

General Procedure for the Preparation of 6 and 7
To a solution of 1-hydroxycarbazole (3a-d, 2.5 mmol) in
dry CH2Cl2, 2-bromobenzoyl chloride, or 2-iodobenzoyl chloride (prepared as before) in dry CH2Cl2 solution (10 mL) was added, and the reaction mixture was heated to reflux for 12 h. The mixture was then washed with H2O and brine solution and dried (Na2SO4). Evaporation of the CH2Cl2 gave a crude product which was purified by chromatography with PE-EtOAc (98:2) to afford 6 and 7.
6-Methyl-9 H -carbazol-1-yl 2-Bromobenzoate (6a) White solid; mp 147 ˚C; yield 0.682 g, 72%. IR (KBr): ν = 3389 (NH), 1741 (OC=O) cm-¹. ¹H NMR (500 MHz, CDCl3): δ = 2.55 (s, 3 H, CH3), 7.24-7.28 (m, 2 H, Harom), 7.35 (d, 1 H, J = 8.0 Hz, H-8), 7.39 (dd, 1 H, J m  = 1.0 Hz, J o  = 8.0 Hz, H-4), 7.46-7.53 (m, 2 H, Harom), 7.81 (dd, 1 H, J m  = 1.5 Hz, J o  = 7.7 Hz, H-2), 7.89 (s, 1 H, H-5), 7.97 (d, 1 H, J = 7.5 Hz, H-3′), 8.13 [dd, 2 H, J m  = 2.0 Hz, J o  = 7.5 Hz, H-6′ (overlapped with NH)]. ¹³C NMR (125 MHz, CDCl3): δ = 21.29 (CH3), 110.66, 117.57, 117.98, 119.24, 120.29, 122.04, 123.52, 126.27, 127.38, 127.66, 129.18, 131.28, 131.68, 131.96, 133.25, 134.54, 135.59, 137.88, 163.93 (C=O). LC-MS: m/z = 380 [M + H+]. Anal. Calcd (%) for C20H14BrNO2: C, 63.32; H, 3.69; N, 3.69. Found: C, 63.36; H, 3.70; N, 3.72.

20

General Procedure for the Preparation of 8
To a mixture of 4 or 5 (1 mmol), Bu4NBr (1.5 equiv), and Cs2CO3 (1.5 equiv) in anhyd DMF (8 mL) was added Pd(OAc)2 (10 mol%) and the flask placed in a pre-heated
oil bath at 110 ˚C for 2 h. After completion of the reaction, the mixture was cooled and diluted with H2O. This was extracted with EtOAc. The combined organic extracts were washed with 1 M HCl, H2O, brine and dried (Na2SO4). The solvent was removed by distillation, and the crude product was purified by column chromatography over silica gel using PE as the eluent to give the final compound 8. 13-Methylbenzo[ f ][1,4]oxazepino[4,3,2- l , m ]carbazol-9-one (8a)
White solid; mp 141 ˚C; yield 0.269 g, 90%. IR (KBr): ν = 1666 (C=O) cm-¹. ¹H NMR (500 MHz, CDCl3): δ = 2.44 (s, 3 H, CH3), 7.12 (d, 1 H, J = 8.0 Hz, H-3), 7.18 (t, 1 H, J = 8.0 Hz, H-2), 7.19 (t, 1 H, J = 7.5 Hz, H-7), 7.23 (d, 1 H, J = 8.0 Hz, H-5), 7.28 (d, 1 H, J = 8.0 Hz, H-12), 7.48 (t, 1 H, J = 7.5 Hz, H-6), 7.60 (d, 1 H, J = 7.0 Hz, H-1), 7.67 (s, 1 H, H-14), 8.05 (dd, 1 H, J m  = 1.5 Hz, J o  = 8.0 Hz, H-8), 8.55 (d, 1 H, J = 8.5 Hz, H-11). ¹³C NMR (125 MHz, CDCl3): δ = 21.42 (CH3), 115.84, 116.94, 117.69, 120.07, 121.34, 124.73, 125.06, 125.52, 126.59, 128.89, 129.27, 129.79, 133.36, 134.51, 134.89, 137.66, 145.62, 156.51, 164.73 (C=O). LC-MS: m/z = 300 [M + H+]. Anal. Calcd (%) for C20H13NO2: C, 80.27; H, 4.35; N, 4.68. Found: C, 80.21; H, 4.37; N, 4.73.

21

Complete cif files for compounds 4a and 9a were deposited with the Cambridge Crystallographic Data Centre, CCDC Deposit numbers 796527 and 796520. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK [fax: +44 (1223)336033 or e-mail: deposit@ccdc.cam.ac.uk].

22

General Procedure for the Preparation of 9
To a mixture of 6 or 7 (1 mmol), Ph3P (20 mol%), and Cs2CO3 (2 equiv) in anhyd DMF (8 mL) was added Pd(OAc)2 (10 mol%), and the mixture was placed in a pre-heated oil bath at 110 ˚C for 4 h. After completion of the reaction, the mixture was cooled and diluted with H2O. This was extracted with EtOAc. The combined organic extracts were washed with 1 M HCl, H2O, brine and dried (Na2SO4). The solvent was removed by distillation, and the crude was purified by column chromatography over silica gel using PE as eluent to give compound 9 as white solid.
10-Methylisochromeno[3,4- a ]carbazol-2(13 H )-one (9a)
Mp >300 ˚C; yield 0.254 g, 85%. IR (KBr): ν = 3305 (NH), 1719 (OC=O) cm-¹. ¹H NMR (500 MHz, CDCl3): δ = 2.49 (s, 3 H, CH3), 7.25 (d, 1 H, J = 8.0 Hz, H-11), 7.37 (d, 1 H, J = 8.0 Hz, H-12), 7.50 (t, 1 H, J = 8.0 Hz, H-4), 7.54 (d, 1 H, J = 8.0 Hz, H-7), 7.78 (d t, 1 H, J m  = 2.0 Hz, J o  = 8.0 Hz, H-5), 7.89 (s, 1 H, H-9), 7.93 (d, 1 H, J = 8.5 Hz, H-3), 8.16 (d, 1 H, J = 8.0 Hz, H-8), 8.38 (dd, 1 H, J m  = 1.5 Hz, J o  = 8.0 Hz, H-6), 8.56 (br s, 1 H, NH). ¹³C NMR (125 MHz, CDCl3): δ = 21.34 (CH3), 102.32, 111.02, 116.10, 118.38, 118.66, 119.20, 120.46, 121.09, 124.52, 125.52, 126.92, 127.15, 128.00, 128.41, 132.07, 132.45, 133.05, 136.76, 158.12 (C=O). LC-MS: m/z = 300 [M + H+]. Anal. Calcd (%) for C20H13NO2: C, 80.27; H, 4.35; N, 4.68. Found: C, 80.17; H, 4.33; N, 4.61.