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

Abstract

Catalytic S_NAr 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 - S_NAr reaction - ruthenium - fluoroarenes - amines

Reference and Notes

• Strong anionic nucleophiles, such as lithium amides and alkoxides, were used in S_NAr reaction of nonactivated haloarenes:
• 1a Huisgen R. Sauer J. Chem. Ber.  1958,  91:  1453 
• 1b Wittig G. Schmidt HJ. Renner H. Chem. Ber.  1962,  95:  2377 
• 1c Rodriguez JR. Agejas J. Bueno AB. Tetrahedron Lett.  2006,  47:  5661 
• 2 Otsuka M. Endo K. Shibata T. Chem. Commun.  2010,  46:  336 
• There had been limited examples of catalytic S_NAr reaction with oxygen nucleophiles using modified cyclopentadienyl rhodium complexes:
• 3a Houghton RP. Voyle M. Price R. J. Chem. Soc., Perkin Trans. 1  1984,  925 
• 3b Goryunov LI. Litvak VV. Shteingarts VD. Zh. Org. Khim.  1987,  23:  1230 
• 4a Semmelhack MF. Chlenov A. Transition Metal Arene π-Complexes in Organic Synthesis and Catalysis   Kündig EP. Springer-Verlag; Berlin / Germany: 2004.  p.43 
• 4b Semmelhack MF. In Comprehensive Organometallic Chemistry II   Vol. 12:  Abel EW. Stone FGA. Wilkinson G. Pergamon; New York: 1995.  p.979 
• For recent examples of the S_NAr reactions of nonactivated fluoroarene with amines using a stoichiometric amount of transition metals, see:
• 5a Braun W. Calmuschi-Cula B. Englert U. Höfener K. Alberico E. Salzer A. Eur. J. Org. Chem.  2008,  12:  2065 
• 5b Kamikawa K. Kinoshita S. Furusyo M. Takemoto S. Matsuzaka H. Uemura M. J. Org. Chem.  2007,  72:  3394 
• 5c Baldoli C. Maiorana S. Licandro E. Casiraghi L. Zinzalla G. Seneci P. Magistris ED. Paio A. Marchioro C. J. Comb. Chem.  2003,  5:  809 
• 6 Takaya J. Hartwig JF. J. Am. Chem. Soc.  2005,  127:  5756 
• Molecular sieves were suggested to operate as solid base:
• 8a Okachi T. Fujimoto K. Onaka M. Org. Lett.  2002,  4:  1667 
• 8b Ono F. Ohta Y. Hasegawa M. Kanemasa S. Tetrahedron Lett.  2009,  50:  2111 
• [Ru(p-cymene)(OTf)(dppben)]OTf [DPPBen: 1,2-bis(diphenylphosphino)benzene] was synthesized and characterized by X-ray single crystal structural analysis:
• 12a Oe Y. Ohta T. Ito Y. Sci. Eng. Rev. Doshisha Univ.  2009,  50:  30 
• 12b Oe Y. Ohta T. Ito Y. Tetrahedron Lett.  2010,  51:  2806 

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%).