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Synlett 2010(17): 2601-2606  
DOI: 10.1055/s-0030-1258774
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Facile Catalytic SNAr Reaction of Nonactivated Fluoroarenes with Amines Using η6-Benzene Ruthenium(II) Complex

Maiko Otsukaa, Hiroya Yokoyamaa, Kohei Endob, Takanori Shibata*a
a Department of Chemistry and Biochemistry, School of Advanced Science and Engineering, Waseda University, Okubo, Shinjuku, Tokyo 169-8555, Japan
b Waseda Institute for Advanced Study, Nishiwaseda, Shinjuku, Tokyo 169-8050, Japan
Fax: +81(3)52868098; e-Mail: tshibata@waseda.jp;
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Publication History

Received 30 July 2010
Publication Date:
30 September 2010 (online)

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Abstract

Catalytic SNAr reaction of fluoroarenes possessing no electron-withdrawing group(s) with cyclic amines was achieved using a readily accessible Ru catalyst, which was prepared from [Ru(benzene)Cl2]2, AgOTf, and P(p-FC6H4)3. The coexistence of molecular sieves MS4A realized high conversion and various substituted aryl amines were obtained in good to high yields.

Key words

catalysis - SNAr reaction - ruthenium - fluoroarenes - amines

    Reference and Notes

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7

Dichloro(p-cymene)ruthenium(II) dimer was also a good precursor and product 3 was obtained in the comparable yield (49%).

9

When 1-allyl-4-fluorobenzene was submitted under the previous conditions (ref. 2), the yield of the styrene derivative was low (21%). Moreover, a hydrogenated by-product also formed, because silane was used as an additive.

10

Excess amounts of fluoroarenes would be needed for efficient arene exchange: when 1-dimethylamino-4-fluorobenzene (3 equiv) was used, the yield significantly decreased to 30%.

11

When the reaction was examined at the higher reaction temperature (160 ˚C), the yield decreased to 25%.

13

The detected isotopic patterns of A, B and C ([M - TfOH]+) by ESI-MS matched with the theoretical isotope patterns.

14

Typical Procedure (Entry 15 in Table 1): Under an atmosphere of argon, MS4A (40 mg) was dried up in a Schlenk tube. To this container, the mixture of [Ru(benzene)Cl2]2 (5.0 mg, 0.010 mmol) and AgOTf (10.8 mg, 0.042 mmol) in acetone was transferred with a syringe filter. After acetone was excluded, a 1,4-dioxane solution (0.10 mL) of P(p-FC6H4)3 (15.2 mg, 0.048 mmol), p-fluorotoluene (220 µL, 2.0 mmol) and morpholine (35 µL, 0.40 mmol) was added. The reaction mixture was stirred under reflux for 24 h, then MS4A was filtered off. After the filtrate was evaporated, the crude products were purified by thin-layer chromatography (hexane-AcOEt = 10:1) to give analytically pure 3 (80%).