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Synlett 2013; 24(17): 2320-2326
DOI: 10.1055/s-0033-1339666
letter
© Georg Thieme Verlag Stuttgart · New York

Microwave-Assisted Efficient Synthesis of Aryl Thioethers through C–H Functionalization of Arenes

Yi-Chen Liu
Department of Chemistry, National Chung Hsing University, Taichung 402, Taiwan   Fax: +886(4)22862547   Email: cfalee@dragon.nchu.edu.tw
,
Chin-Fa Lee*
Department of Chemistry, National Chung Hsing University, Taichung 402, Taiwan   Fax: +886(4)22862547   Email: cfalee@dragon.nchu.edu.tw
› Author Affiliations
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Publication History

Received: 21 July 2013

Accepted: 03 August 2013

Publication Date:
13 September 2013 (online)

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Abstract

Microwave-assisted iridium-catalyzed meta C–H borylation followed by copper-promoted C–S bond coupling reactions in one pot is reported. This approach enables the syntheses of aryl thioethers in short reaction times (within 2.5 hours). The system shows good functional-group compatibility, as chloro, trifluoromethyl, fluoro, and pyridine groups are tolerated by the reaction conditions. Both aryl and alkyl thiols are coupled smoothly. The products were formed with excellent regioselectivity in meta position.

Key words

microwave - aryl thioether - iridium - copper - C–H functionalization - arene

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
  • Supporting Information
 

  • References and Notes

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  • 28 General Procedure for the Synthesis of Compounds 2a–q A flask equipped with a magnetic stirrer bar was charged with [Ir(cod)OMe)]2 (99.0 mg, 0.015 mmol), 4,4′-di-tert-butyl-2,2′-dipyridyl (82.0 mg, 0.03 mmol) and pin2B2 (254 mg, 1.0 mmol) in a nitrogen-filled glove box. This flask was then covered with a rubber septum and removed from the glove box. Under a nitrogen atmosphere, arene (1.0 mmol) and MTBE (2.0 mL) were added via syringe, and the reaction vessel was placed under microwave irradiation at 80 °C. After stirring at this temperature for 1 h, the heterogeneous mixture was cooled to r.t., after removal of the volatile components under vacuum. The flask was returned to the glove box, Cu(OAc)2 (136 mg, 0.75 mmol) was added, the flask was then covered with a rubber septum and removed from the glove box. Under an argon atmosphere, aryl thiol (0.5 mmol), pyridine (0.123 mL, 1.5 mmol), and DMF (2.0 mL) were added via syringe, and the reaction vessel was placed under microwave irradiation at 135 °C. After stirring at this temperature for 1.5 h, the heterogeneous mixture was cooled to r.t. and diluted with EtOAc (20 mL). The resulting solution was directly filtered through a pad of silica gel then washed with EtOAc (20 mL) and concentrated to give the crude material which was then purified by column chromatography (SiO2, hexane) to yield 2. Data for some representative examples are shown here. 3-Chloro-5-methylphenyl Phenyl Sulfide (2a) 21a Following the general procedure, using [Ir(cod)OMe]2 (99.0 mg, 0.015 mmol), 4,4′-di-tert-butyl-2,2′-dipyridyl (82.0 mg, 0.03 mmol), pin2B2 (254 mg, 1.0 mmol), and 3-chlorotoluene (0.123 mL, 1.0 mmol) in MTBE (2.0 mL) for the first step. After removal of the volatile components under vacuum, Cu(OAc)2 (136 mg, 0.75 mmol), thiophenol (0.053 mL, 0.5 mmol), and DMF (2.0 mL) were used, then purified by column chromatography (SiO2, hexane) to provide 2a as a colorless oil (70.0 mg, 60% yield). 1H NMR (400 MHz, CDCl3): δ = 2.23 (s, 3 H), 6.97–7.04 (m, 3 H), 7,25–7.38 (m, 5 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 21.0, 126.6, 127.5, 127.7, 128.7, 129.3, 132.0, 134.1, 134.4, 138.0, 140.4 ppm. 3-Chloro-5-methylphenyl 4-Methoxyphenyl Sulfide (2b) 21a Following the general procedure, using [Ir(cod)OMe)]2 (99.0 mg, 0.015 mmol), 4,4′-di-tert-butyl-2,2′-dipyridyl (82.0 mg, 0.03 mmol), pin2B2 (254 mg, 1.0 mmol), and 3-chlorotoluene (0.123 mL, 1.0 mmol) in MTBE (2.0 mL) for the first step. After removal of the volatile components under vacuum, Cu(OAc)2 (136 mg, 0.75 mmol), 4-methoxy-thiophenol (0.063 mL, 0.5 mmol), and DMF (2.0 mL) were used, then purified by column chromatography (SiO2, hexane) to provide 2b as a colorless oil (62.0 mg, 47% yield). 1H NMR (400 MHz, CDCl3): δ = 2.20 (s, 3 H), 3.78 (s, 3 H), 6.82–6.90 (m, 5 H), 7.39–7.41 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 21.1, 55.2, 115.0, 122.7, 124.0, 126.1, 126.3, 134.3, 136.0, 140.1, 140.7, 160.1 ppm. 3-Chloro-5-methylphenyl 3-Trifluoromethyl Phenyl Sulfide (2c) Following the general procedure, using [Ir(cod)OMe]2 (99.0 mg, 0.015 mmol), 4,4′-di-tert-butyl-2,2′-dipyridyl (82.0 mg, 0.03 mmol), pin2B2 (254 mg, 1.0 mmol), and 3-chlorotoluene (0.123 mL, 1.0 mmol) in MTBE (2.0 mL) for the first step. After removal of the volatile components under vacuum, Cu(OAc)2 (136 mg, 0.75 mmol), 3-trifluoro-methylthiophenol (0.070 mL, 0.5 mmol), and DMF (2.0 mL) were used, then purified by column chromatography (SiO2, hexane) to provide 2c as a colorless oil (118.0 mg, 78% yield). 1H NMR (400 MHz, CDCl3): δ = 2.29 (s, 3 H), 7.08 (d, J = 7.6 Hz, 2 H), 7.14 (s, 1 H), 7.40–7.49 (m, 3 H), 7.58 (s, 1 H) ppm. 13C NMR (150 MHz, CDCl3): δ = 123.6 (q, J = 271.1 Hz), 123.9 (q, J = 3.7 Hz), 127.1 (q, J = 3.9 Hz) 128.3, 128.8, 129.7, 130.3, 131.6 (q, J = 32.4 Hz), 133.7, 134.8, 135.6, 136.9, 141.0 ppm. 19F NMR (376 MHz, CDCl3): δ = –64.4 (s) ppm. HRMS (EI): m/z calcd for C14H10F3ClS: 302.0144; found: 302.0148. 3-Chloro-5-methylphenyl 4-Chlorophenyl Sulfide (2d) 21a Following the general procedure, using [Ir(cod)OMe)]2 (99.0 mg, 0.015 mmol), 4,4′-di-tert-butyl-2,2′-dipyridyl (82.0 mg, 0.03 mmol), pin2B2 (254 mg, 1.0 mmol), and 3-chlorotoluene (0.123 mL, 1.0 mmol) in MTBE (2.0 mL) for the first step. After removal of the volatile components under vacuum, Cu(OAc)2 (136 mg, 0.75 mmol), 4-chlorothio-phenol (74 mg, 0.5 mmol), and DMF (2.0 mL) were used, then purified by column chromatography (SiO2, hexane) to provide 2d as a colorless oil (0.081 g, 65% yield). 1H NMR (400 MHz, CDCl3): δ = 2.27 (s, 3 H), 6.98 (s, 1 H), 7.03 (s, 1 H), 7.05 (s, 1 H), 7.29 (s, 4 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 21.1, 127.0, 128.0, 129.1, 129.5, 133.0, 133.1, 133.8, 134.6, 137.3, 140.7 ppm. 3-Chloro-5-methylphenyl 4-Fluorophenyl Sulfide (2e) 21b Following the general procedure, using [Ir(cod)OMe)]2 (99.0 mg, 0.015 mmol), 4,4′-di-tert-butyl-2,2′-dipyridyl (82.0 mg, 0.03 mmol), pin2B2 (254 mg, 1.0 mmol), and 3-chlorotoluene (0.123 mL, 1.0 mmol) in MTBE (2.0 mL) for the first step. After removal of the volatile components under vacuum, Cu(OAc)2 (0.1362 g, 0.75 mmol), 4-fluoro-thiophenol (0.055 mL, 0.5 mmol), and DMF (2.0 mL) were used, then purified by column chromatography (SiO2, hexane) to provide 2e as a colorless oil (63.0 mg, 50% yield). 1H NMR (400 MHz, CDCl3): δ = 2.26 (s, 3 H), 6.91 (s, 1 H), 6.95 (s, 1 H), 6.98 (s, 1 H), 7.03–7.08 (m, 2 H), 7.40–7.43 (m, 2 H) ppm. 13C NMR (150 MHz, CDCl3): δ = 21.1, 116.6, 116.7, 125.7, 127.3, 127.8, 128.7, 128.7, 134.6, 135.0, 135.0, 138.8, 140.5, 161.9, 163.6 ppm. 19F NMR (376 MHz, CDCl3): δ = –114.3 (s) ppm.