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Synlett 2008(3): 377-380  
DOI: 10.1055/s-2008-1032066
LETTER
© Georg Thieme Verlag Stuttgart · New York

One-Pot Synthesis of Carbazole via Tandem Suzuki-Miyaura and Amination Reaction

Yuki Kitamura, Seiji Yoshikawa, Takumi Furuta, Toshiyuki Kan*
School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan
Fax: +81(54)2645745; e-Mail: kant@u-shizuoka-ken.ac.jp;
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Publication History

Received 10 October 2007
Publication Date:
23 January 2008 (online)

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Abstract

One-pot synthesis of carbazole from two aromatic rings was accomplished by a tandem Suzuki-Miyaura and amination reaction. Our novel phosphine ligand for both reactions efficiently mediates a sequential intermolecular biaryl formation and ring-closing amination.

Key words

phenylnaphthyl phosphane - intramolecular amination - Suzuki-Miyaura cross-coupling - carbazole

9

We have found that a Suzuki-Miyaura reaction of 12 and 13 mediated by ligand 1 provides biaryl product 14 even with the chloride, which is known as a low reactive halide (Scheme [2] ).

Scheme 2

10

Experimental Procedure for the Synthesis of Carbazole 5 (Table 1, Entry 6)
To a solution of 2-bromophenylboronic acid (2, 30 mg, 0.15 mmol) and 2-iodoaniline (3, 30 mg, 0.14 mmol) in toluene (0.5 mL) was added Pd2 (dba)3 (13 mg, 0.01 mmol), ligand 1 (6.9 mg, 0.02 mmol), and Cs2CO3 (134 mg, 0.41 mmol) at r.t. under an argon atmosphere, then the mixture was stirred at 100 °C for 2 h. The mixture was cooled to r.t., and then NaOt-Bu (16 mg, 0.17 mmol) was added and stirred at 100 °C for 19 h. After stirring, H2O was added, and extracted with EtOAc. The organic layer was washed with H2O, brine, dried over MgSO4 and evaporated. The residue was purified by column chromatography on silica gel (benzene-EtOAc, 99:1) to afford the 9H-carbazole (5, 16 mg, 71%) as a colorless solid; R f = 0.82 (benzene-EtOAc, 99:1). 1H NMR (500 MHz, CDCl3): δ = 8.08 (d, J = 7.9 Hz, 2 H), 8.03 (br s, 1 H), 7.50-7.40 (m, 4 H), 7.30-7.20 (m, 2 H). 13C NMR (68 MHz, CDCl3): δ = 139.5, 125.8, 123.4, 120.3, 119.4, 110.6. MS-FAB: m/z = 168 [M + H]+. HRMS-FAB: m/z calcd for C12H10N [M + H]+: 168.0814; found: 168.0809.

11

An isolation and structure determination of complex 4′ was not tested.

12

Addition of Cs2CO3 (1.2 equiv) instead of NaOt-Bu gave no improvement of chemical yields to give 5 and 4 in 26% and 31%, respectively. This result also supports that the complex 4′ plays a role in preventing the ring closure to 5.

14

Analytical Data of 9b
R f = 0.52 (hexane-benzene, 2:3). 1H NMR (500 MHz, CDCl3): δ = 8.34 (s, 1 H), 8.23 (br s, 1 H), 8.10 (d, J = 7.9 Hz, 1 H), 7.66 (d, J = 8.5 Hz, 1 H), 7.55-7.40 (m, 3 H), 7.35-7.25 (m, 1 H). 13C NMR (68 MHz, CDCl3): δ = 140.9, 139.4, 127.3, 126.8, 123.2, 123.0, 122.9, 122.8, 122.72, 122.67, 122.6, 122.0, 121.6, 120.6, 120.3, 118.02, 117.96, 117.9, 117.8, 110.9, 110.6. MS-FAB: m/z = 236 [M + H]+. HRMS-FAB: m/z calcd for C13H9NF3 [M + H]+ 236.0687; found: 236.0678.
Analytical Data of 9g
R f = 0.20 (hexane-CH2Cl2, 1:1). 1H NMR (500 MHz, CDCl3): δ = 7.94 (d, J = 7.9 Hz, 1 H), 7.87 (br s, 1 H), 7.51 (s, 1 H), 7.40-7.25 (m, 2 H), 7.24-7.15 (m, 1 H), 6.87 (s, 1 H), 4.00 (s, 3 H), 3.93 (s, 3 H). 13C NMR (68 MHz, CDCl3): δ = 149.4, 144.4, 139.4, 134.2, 124.2, 123.6, 119.20, 119.18, 115.3, 110.5, 102.7, 94.2, 56.6, 56.1. MS-FAB: m/z = 227 [M + H]+. HRMS-FAB: m/z calcd for C14H14NO2 [M + H]+ 228.1025; found: 228.1022.

17

The carbazole synthesis from aniline and 1,2-dihalobenzene was reported in ref. 6b.

18

Experimental Procedure (Table 4, entry 2)
To a solution of 2-aminophenylboronic acid (10, 15 mg, 0.11 mmol) and 1,2-diiodobenzene (11, 33 mg, 0.10 mmol) in 1,4-dioxane (0.33 mL) was added Pd(OAc)2 (2.2 mg, 0.01 mmol), ligand 1 (5.0 mg, 0.01 mmol), and Cs2CO3 (98 mg, 0.30 mmol) at r.t. under an argon atmosphere, then the mixture was stirred at 80 °C for 24 h. The mixture was cool to r.t., and then NaOt-Bu (12 mg, 0.12 mmol) was added and stirred at 80 °C for 24 h. After stirring, H2O was added, and extracted with EtOAc. The organic layer was washed with H2O, brine, dried over MgSO4, and evaporated. The residue was purified by column chromatography on silica gel (benzene-EtOAc, 99:1) to afford the 9H-carbazole (5, 13 mg, 76%) as a colorless solid.