Synlett 2007(2): 0247-0250  
DOI: 10.1055/s-2007-968013
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Manganese-Catalyzed Cross-Coupling Reaction

Magnus Rueping*, Winai Ieawsuwan
Degussa Endowed Professorship, Institute of Organic Chemistry and Chemical Biology, Johann-Wolfgang Goethe University Frankfurt, Max-von-Laue Straße 7, 60438 Frankfurt, Germany
Fax: +49(69)79829248; e-Mail: M.Rueping@chemie.uni-frankfurt.de;
Further Information

Publication History

Received 20 October 2006
Publication Date:
24 January 2007 (online)

Abstract

A manganese-catalyzed cross-coupling reaction of ­heterocyclic chlorides with aryl- as well as alkylmagnesium halides has been developed. The reaction provides a variety of heterocyclic compounds under mild and practical reaction conditions using low amounts of manganese chloride as catalyst.

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For the reactions reported commercially available MnCl2 salts were applied. MnCl2 anhyd (Aldrich 99.999%), MnCl2·4H2O (Strem 99.999%) and MnCl2 (Aldrich 98%) gave the same results in the cross-coupling reactions.

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Typical Procedure: Preparation of 4-Isopropyl-2-phenylquinoline ( 3k).
A two-necked round-bottomed flask was charged under Ar with 4-chloro-2-phenylquinoline (0.2397 g, 1.00 mmol), MnCl2 (6.3 mg, 50 µmol) and THF (5mL) and cooled to 0 °C. The Grignard reagent i-PrMgCl (1.25 mL, 1.20 M in THF, 1.50 mmol) was added slowly via a syringe and the reaction mixture was stirred at 0 °C for 4 h. The reaction mixture was quenched with sat. NH4Cl (5 mL) and H2O (5 mL) at 0 °C, extracted with EtOAc (3 × 25 mL), and dried over Mg(SO4). After removal of solvents in vacuo, the crude product was purified by column chromatography (hexane-EtOAc, 50:1) to give the product as a pale yellow oil (0.1887 g, 81%). 1H NMR (250 MHz, CDCl3): δ = 8.12 (d, J = 8.5 Hz, 1 H, ArH), 8.10-8.02 (m, 2 H, ArH), 7.99 (d, J = 8.3 Hz, 1 H, ArH), 7.68 (s, 1 H, ArH), 7.64-7.55 (m, 1 H, ArH), 7.47-7.32 (m, 4 H, ArH), 3.68 [sept, J = 6.8 Hz, 1 H, CH(CH3)2], 1.35 [d, J = 6.8 Hz, 6 H, CH(CH3)2]. 13C NMR (63 MHz, CDCl3): δ = 157.4 (C), 155.0 (C), 148.6 (C), 140.3 (C), 130.7 (CH), 129.2 (CH), 129.1 (CH), 128.8 (CH), 127.7 (CH), 126.0 (CH), 125.9 (C), 123.0 (CH), 115.0 (CH), 28.6 (CH), 23.1 (CH3). IR (neat): ν = 3061 (m), 2865 (s), 2930 (m), 2871 (w), 1596 (s), 1551 (s), 1508 (m), 1494 (s), 1460 (m), 1445 (m), 1414 (w), 1385 (m), 1364 (w), 1347 (s), 1234 (w), 1181 (w), 1071 (w), 1029 (w), 907 (w), 879 (m), 838 (w), 792 (m), 770 (s), 694 (s) cm-1. ESI-MS: m/z = 248 [M + H]+. Anal. Calcd for C18H17N: C, 87.41; H, 6.93; N, 5.66. Found: C, 87.59; H, 7.04; N, 5.45.
Preparation of 4-( p -Tolyl)quinoline ( 3y).
A two-necked round-bottomed flask, equipped with a reflux condenser and dropping funnel, was charged with Mg (63.2 mg, 2.60 mmol) and THF (8 mL) under Ar and a solution of p-bromotoluene (0.4276 g, 2.50 mmol) in THF (5 mL) was added dropwise (15 min). Subsequently, the reaction mixture was refluxed for 1 h and cooled to 0 °C. A solution of 4-chloroquinoline (0.1636 g, 1.00 mmol) in THF (3 mL) was added via syringe to the reaction mixture and MnCl2 (2.5 mg, 20 µmol) was quickly added. The resulting solution was stirred at 0 °C for 2 h, quenched with sat. NH4Cl (5 mL) and H2O (5 mL) at 0 °C, extracted with EtOAc (3 × 25 mL), and dried over Mg(SO4). After removal of solvents in vacuo, the crude product was purified by silica gel column chromatography (hexane-EtOAc, 5:1) to provide the product as a pale yellow oil (0.1857 g, 85%). 1H NMR (250 MHz, CDCl3): δ = 8.05 (d, J = 8.5 Hz, 1 H, ArH), 8.79 (d, J = 4.5 Hz, 1 H, ArH), 7.81 (d, J = 8.3 Hz, 1 H, ArH), 7.61-7.78 (m, 1 H, ArH), 7.37-7.28 (m, 1 H, ArH), 7.28-7.14 (m, 5 H, ArH), 2.31 (s, 3 H, CH3). 13C NMR (63 MHz, CDCl3): δ = 150.0 (CH), 148.8 (C), 148.5 (C), 138.4 (C), 135.1 (C), 129.9 (CH), 129.5 (CH), 129.3 (CH), 129.2 (CH), 126.9 (C), 126.5 (CH), 126.0 (CH), 121.3 (CH), 21.3 (CH3). IR (neat): ν = 3027 (m), 2920 (m), 1614 (m), 1586 (s), 1569 (s), 1501 (s), 1459 (w), 1421 (m), 1389 (m), 1275 (w), 1112 (w), 1021 (w), 872 (w), 819 (s), 765 (s), 721 (w), 674 (m), 661 (w) cm-1. ESI-MS: m/z = 220 [M + H]+. Anal. Calcd for C16H13N: C, 87.64; H, 5.98; N, 6.39. Found: C, 87.53; H, 6.15; N, 6.29.