A Manganese-Catalyzed Cross-Coupling Reaction

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.

Key words

manganese catalysis - cross-coupling - arylation - alkylation - heterocycles - pyridine - quinoline

References and Notes

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• Organocatalytic reductions of quinolines and imines:
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• 8 For an earlier report on functional-group-directed manganese-catalyzed cross-coupling with activated aryl chlorides, see: Cahiez G. Lepifre F. Ramiandrasoa P. Synthesis  1999,  2138 

9

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.

10

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.