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Synlett 2009(6): 955-959  
DOI: 10.1055/s-0028-1088199
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

O-Aryloxime Ethers from the Copper(II)-Mediated Cross-Coupling of Oximes and Phenylboronic Acids

Abdelselam Alia,b, Adam G. Meyer*a, Kellie L. Tuckb
a CSIRO Molecular and Health Technologies, Bag 10, Clayton South, Vic 3169, Australia
Fax: +61(3)95452376; e-Mail: adam.meyer@csiro.au;
b School of Chemistry, Monash University, Clayton, Vic 3800, Australia
Further Information

Publication History

Received 28 October 2008
Publication Date:
16 March 2009 (online)

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Abstract

A direct approach to O-aryloxime ethers by means of the first copper-mediated cross-coupling of aromatic oximes and phenylboronic acids is reported. The O-arylation of acetophenone oximes with phenylboronic acids typically furnished O-aryloxime ethers in good to moderate yields.

Key words

O-aryloxime ether - oxime - phenylboronic acid - copper(II) acetate - cross-coupling

    References and Notes

  • 1a Sheradsky T. Tetrahedron Lett.  1966,  43:  5225 
    Google Scholar
  • 1b Castellino AJ. Rapoport H. J. Org. Chem.  1984,  49:  4399 
    Google Scholar
  • 1c Takeda N. Miyata O. Naito T. Eur. J. Org. Chem.  2007,  1491 
    Google Scholar
  • 2a Shutske GM. J. Org. Chem.  1984,  49:  180 
    Google Scholar
  • 2b Shutske GM. Kapples KJ. J. Heterocycl. Chem.  1989,  26:  1293 
    Google Scholar
  • 3 Johnson SM. Petrassi HM. Palaninathan SK. Mohamedmohaideen NN. Purkey HE. Nichols C. Chiang KP. Walkup T. Sacchettini JC. Sharpless KB. Kelly JW. J. Med. Chem.  2005,  48:  1576 
    CrossrefGoogle Scholar
  • 4a Meyer AG, Winzenberg KN, Sawutz DG, and Liepa AJ. inventors; US 7 312  248. 
  • 4b Ali A. Altamore TM. Bliese M. Fisara P. Liepa AJ. Meyer AG. Nguyen O. Sargent RM. Sawutz DG. Winkler DA. Winzenberg KN. Ziebell A. Bioorg. Med. Chem. Lett.  2008,  18:  252 
    Google Scholar
  • 5 Ãbele E. Lukevics E. Org. Prep. Proced. Int.  2000,  32:  235 
    CrossrefGoogle Scholar
  • 6a Mooradian A. DuPont PE. J. Heterocycl. Chem.  1967,  4:  441 
    Google Scholar
  • 6b Jacob BB. Synthesis  1975,  782 
    Google Scholar
  • 7A copper-catalyzed cross-coupling of aromatic oximes with iodoarenes has recently been reported. See:
  • 7 De Nonappa P. Pandurangan K. Maitra U. Wailes S. Org. Lett.  2007,  9:  2767 
    CrossrefGoogle Scholar
  • 8 Chan DMT. Monaco KL. Wang R.-P. Winters MP. Tetrahedron Lett.  1998,  39:  2933 
    CrossrefGoogle Scholar
  • 9 Evans DA. Katz JL. West TR. Tetrahedron Lett.  1998,  39:  2937 
    CrossrefGoogle Scholar
  • 10a Petrassi HM. Sharpless KB. Kelly JW. Org. Lett.  2001,  3:  139 
    Google Scholar
  • 10b Wang Z. Zhang J. Tetrahedron Lett.  2005,  46:  4997 
    Google Scholar
  • 10c Singh BK. Appukkuttan P. Claerhout S. Parmar VS. Van der Eycken E. Org. Lett.  2006,  8:  1863 
    Google Scholar
  • 13 Chan DMT. Monaco KL. Li R. Bonne D. Clark CG. Lam PYS. Tetrahedron Lett.  2003,  44:  3863 
    CrossrefGoogle Scholar
  • 14 2-Halophenylboronic acids are presumably susceptible to ‘proto-deboronation’. See: Kuivila HG. Reuwer JF. Mangravite JA. J. Am Chem. Soc.  1964,  86:  2666 
    CrossrefGoogle Scholar
  • 15a Kaminskaia NV. Kostic NM. J. Chem. Soc., Dalton Trans.  2001,  1083 
    Google Scholar
  • 15b Onindo CO. Kozlowski H. Kiss T. J. Chem. Soc., Dalton Trans.  1995,  3911 
    Google Scholar
11

All products showed analytical and spectral characteristics consistent with their structure.
Representative Pocedure for the Copper-Mediated Cross-Coupling of Aromatic Oximes and Phenylboronic Acids
To a mixture of acetophenone oxime (1a, 200 mg, 1.48 mmol), Cu(OAc)2 (269 mg, 1.48 mmol) and 4-chloro-phenylboronic acid (2a, 463 mg, 2.96 mmol) in DCE (12 mL) was added pyridine (239 µL, 2.96 mmol). This resulted in a light green colored solution to which freshly activated, and partially crushed, 4 Å MS (ca. 350 mg) were added. The reaction was open to the atmosphere. The progress of the reaction was followed by TLC. The color of the reaction mixture changed from light to deep green as the reaction proceeded. After stirring at r.t. for 72 h the reaction mixture was filtered through a small pad of silica gel (eluting with CH2Cl2) and the solvent removed under reduced pressure. The resulting brown oil was purified by radial chromatography (eluting with 5-10% CH2Cl2-PE) to afford (E)-O-(4-chlorophenyl)acetophenone oxime (3a, 215 mg, 59%) as a white solid; mp 69-71 ˚C (lit. [7] 54-56 ˚C). ¹H NMR (400 MHz, CDCl3): δ = 7.76 (m, 2 H), 7.43 (m, 3 H), 7.29 (d, J = 9.2 Hz, 2 H), 7.23 (d, J = 9.2 Hz, 2 H), 2.45 (s, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 158.2 (C), 158.1 (C), 135.7 (C), 129.9 (CH), 129.1 (CH), 128.5 (CH), 126.9 (C), 126.5 (CH), 116.0 (CH), 13.4 (CH3). HRMS: m/z calcd for C14H12ClNO: 245.0607; found: 245.0599.
Data for Selected Compounds
( E )- O -(3-Chlorophenyl)acetophenone Oxime (3b)
Colorless oil. ¹H NMR (400 MHz, CDCl3): δ = 7.77 (m,
2 H), 7.43 (m, 3 H), 7.35 (m, 1 H), 7.24 (m, 1 H), 7.15 (m,
1 H), 7.01 (m, 1 H), 2.45 (s, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 160.2 (C), 158.5 (C), 135.6 (C), 134.7 (C), 130.0 (CH), 129.9 (CH), 128.5 (CH), 126.5 (CH), 122.2 (CH), 115.2 (CH), 113.0 (CH), 13.4 (CH3). HRMS: m/z calcd for C14H12ClNO: 245.0607; found: 245.0606.

( E )- O -(4-Chlorophenyl)-4′-chloroacetophenone Oxime (4a)
Colorless solid; mp 81-83 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 7.70 (d, J = 8.4 Hz, 2 H), 7.39 (d, J = 8.4 Hz, 2 H), 7.29 (d, J = 8.8 Hz, 2 H), 7.21 (d, J = 8.8 Hz, 2 H), 2.42 (s, 3 H). ¹³C NMR (50 MHz, CDCl3): δ = 158.0 (C), 157.1 (C), 136.0 (C), 134.1 (C), 129.2 (CH), 128.8 (CH), 127.7 (CH), 127.1 (C), 116.0 (CH), 13.3 (CH3). HRMS: m/z calcd for C14H11Cl2NO: 279.0218; found: 279.0207.
( E )- O -(4-Methylphenyl)-4′-chloroacetophenone Oxime (4f)
Yellow solid; mp 103-104 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 7.71 (d, J = 8.8 Hz, 2 H), 7.38 (d, J = 8.8 Hz, 2 H), 7.14 (m, 4 H), 2.42 (s, 3 H), 2.32 (s, 3 H). ¹³C NMR (125 MHz, CDCl3): δ = 157.4 (C), 156.2 (C), 135.6 (C), 134.5 (C), 131.7 (C), 129.7 (CH), 128.7 (CH), 127.7 (CH), 114.7 (CH), 20.6 (CH3), 13.1 (CH3). HRMS: m/z calcd for C15H14ClNO: 259.0764; found: 259.0766.
( E )- O -(4-Chlorophenyl)-4′-nitroacetophenone Oxime (4g)
Colorless solid; mp 101-103 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 8.26 (d, J = 9.2 Hz, 2 H), 7.93 (d, J = 9.2 Hz, 2 H), 7.30 (d, J = 9.2 Hz, 2 H), 7.22 (d, J = 9.2 Hz, 2 H), 2.49 (s, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 157.8 (C), 156.2 (C), 148.5 (C), 141.6 (C), 129.3 (CH), 127.6 (C), 127.2 (CH), 123.7 (CH), 116.1 (CH), 13.3 (CH3). HRMS: m/z calcd for C14H11ClN2O3: 290.0458; found: 290.0446.

























( E )- O -(3-Methoxyphenyl)-4′-nitroacetophenone Oxime (4k)

Colorless solid; mp 76-78 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 8.28 (d, J = 8.8 Hz, 2 H), 7.96 (d, J = 8.8 Hz, 2 H), 7.26 (m, 1 H), 6.89 (m, 2 H), 6.64 (m, 1 H), 3.84 (s, 3 H), 2.50 (s, 3 H). ¹³C NMR (50 MHz, CDCl3): δ = 160.7 (C), 160.3 (C), 155.7 (C), 148.5 (C), 141.9 (C), 129.9 (CH), 127.2 (CH), 123.7 (CH), 108.2 (CH), 107.2 (CH), 101.1 (CH), 55.4 (CH3), 13.2 (CH3). HRMS: m/z calcd for C15H14N2O4: 286.0954; found: 286.0945.
( E )- O -(4-Chlorophenyl)-4′-methoxyacetophenone Oxime (4m)
Colorless solid; mp 78-80 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 7.72 (d, J = 8.8 Hz, 2 H), 7.27 (d, J = 9.2 Hz, 2 H), 7.21 (d, J = 9.2 Hz, 2 H), 6.94 (d, J = 8.8 Hz, 2 H), 3.85 (s, 3 H), 2.41 (s, CH3). ¹³C NMR (100 MHz, CDCl3): δ = 161.0 (C), 158.2 (C), 157.8 (C), 129.1 (CH), 128.1 (C), 127.9 (CH), 126.7 (C), 116.0 (CH), 113.9 (CH), 55.3 (CH3), 13.3 (CH3). HRMS: m/z calcd for C15H14ClNO2: 275.0713; found: 275.0698.

12

In the case of compounds 3h and 3i, DBU (2.0 equiv) was found to be a more effective amine than pyridine.