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Synlett 2005(1): 127-133  
DOI: 10.1055/s-2004-836030
LETTER
© Georg Thieme Verlag Stuttgart · New York

Microwave-Enhanced Cadogan Cyclization: An Easy Access to the 2-Substituted Carbazoles and other Fused Heterocyclic Systems

Prasad Appukkuttan, Erik Van der Eycken, Wim Dehaen*
Departement of Chemistry, K. U. Leuven, Celestijnenlaan 200F, 3001 Leuven, Belgium
Fax: +32(16)327990; e-Mail: wim.dehaen@chem.kuleuven.ac.be;
Further Information

Publication History

Received 14 September 2004
Publication Date:
29 November 2004 (online)

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Abstract

A microwave-enhanced Suzuki-Miyaura cross-coupling reaction in combination with a microwave-assisted Cadogan reductive cyclization is presented as an easy access to a variety of 2-substituted carbazoles and other fused heterocyclic systems. Microwave irradiation was found very useful in minimizing the proto-deboronation issues in the cross-coupling reaction, and enhances the rate of reductive cyclization in a dramatic manner.

Key words

microwave-enhanced - Suzuki-Miyaura cross-coupling reaction - Cadogan reductive cyclization

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CEM-Discover, CEM Corporation P.O. Box 200 Matthews, NC 28106.

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General Procedure for the Microwave-Enhanced Suzuki Reaction and Cadogan Cyclization - Synthesis of 8 H -Thieno[2,3- b ]indole ( 4q): 3-Bromothiophene (2q, 0.041 g, 0.25 mmol), 2-nitrophenylboronic acid (0.054 g, 0.325 mmol), NaHCO3 (0.063 g, 0.75 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.015 g, 5 mol%) were suspended in DMF (1.5 mL) and H2O (1.5 mL) in a 10 mL glass vial equipped with a small stirring magnet. The vial was sealed tightly with an aluminium-Teflon® crimp top and the mixture was irradiated in the cavity of a mono-mode CEM®-Discover machine for 15 min at a pre-selected temperature of 150 °C, using a maximum irradiation power of 100 W. After the reaction, the vial was cooled to 50 °C by gas jet cooling. The crude mixture was partitioned between Et2O and H2O (25 mL each) and the aqueous layer was extracted with Et2O (3 × 20 mL). The combined organic layers were dried on MgSO4 and solvents were removed under vacuum to yield the crude product as yellow oil. Column chromatography [silica gel, heptane-EtOAc (9:1)] afforded the biaryl compound 3q (0.046 g, 890%) as yellowish oily material.
The nitro compound 3q was suspended in triethyl phosphate (3 mL) in a tightly sealed 10 mL glass vial and was irradiated at a maximum irradiation power of 300 W for 15 min at a pre-selected temperature of 210 °C. After the reaction, the vial was cooled to 50 °C by gas jet cooling and the contents were transferred to a 50 mL flask with the help of EtOAc (10 mL). This mixture was then heated to 80 °C with an excess of HCl (6 N, 10 mL) and maintained at the temperature for 3 h. After cooling to r.t., the mixture was partitioned between H2O and EtOAc (20 mL each) and the aqueous layer was further extracted with EtOAc (3 × 10 mL). The combined organic layers were dried over MgSO4 and solvents were removed under reduced pressure, and further purification by column chromatography (silica gel, heptane-EtOAc, 9:1) afforded the thieno-indole 4q (0.0296 g, 76%). 1H NMR (300 MHz, CDCl3): δ = 6.92 (d, 1 H, J = 5.2 Hz), 7.19-7.27 (m, 2 H), 7.36 (d, 1 H, J = 5.2 Hz), 7.41 (d, 1 H, J = 8.0 Hz), 7.81 (dd, 1 H, J = 7.6, 0.8 Hz), 8.22 (br s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 111.2, 117.1, 117.6, 119.3, 119.9, 122.2, 122.5, 125.6, 141.2, 142.2 ppm. DEPT-NMR (75 MHz, CDCl3): δ = 111.2, 117.1, 117.6, 119.3, 122.5, 125.6 ppm. MS (EI): 173 [M+]. HRMS (EI): m/z calcd for C10H07NS [M+]: 173.02992; found: 173.02986.