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Synlett 2012; 23(17): 2477-2480
DOI: 10.1055/s-0032-1317205
letter
© Georg Thieme Verlag Stuttgart · New York

Microwave-Mediated Suzuki–Miyaura Cross-Couplings of Thioether- and ortho-Substituted Methylphenylboronic Acid Esters

Christine B. Baltus
a   School of Science, University of Greenwich at Medway, University of Greenwich, Chatham Maritime, Kent, ME4 4TB, UK
,
Neil J. Press
b   Novartis Pharmaceuticals UK Ltd, Horsham, Sussex, RH12 5AB, UK   Fax: +44(1273)876687   Email: j.spencer@sussex.ac.uk
,
John Spencer*
a   School of Science, University of Greenwich at Medway, University of Greenwich, Chatham Maritime, Kent, ME4 4TB, UK
› Author Affiliations
Further Information

Publication History

Received: 04 July 2012

Accepted after revision: 14 August 2012

Publication Date:
21 September 2012 (online)

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Abstract

Hiterto unsuccessful cross-couplings of ortho-substituted or thioether-substituted methylphenylboronates have now been achieved, under microwave conditions, enabling the synthesis of a library of novel biaryls. Tetrakis(triphenylphosphine)palladium and various bases, for example, sodium carbonate or cesium fluoride, were found to mediate the crucial C–C bond-forming cross-­coupling reaction.

Key words

palladium - catalysis - cross-coupling - biaryls - microwaves

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
  • Supporting Information
 

  • References and Notes

  • 1 Current address: Department of Chemistry, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QJ, UK.
    • 2a Spencer J, Baltus CB, Patel H, Press NJ, Callear SK, Male L, Coles SJ. ACS Comb. Sci. 2011; 13: 24
      Crossref
    • 2b Spencer J, Burd AP, Adatia T, Goodwin CA, Merette SA. M, Scully MF, Deadman JJ. Tetrahedron 2002; 58: 1551
      Crossref
    • 2c Spencer J, Baltus CB, Press NJ, Harrington RW, Clegg W. Tetrahedron Lett. 2011; 52: 3963
      Crossref
  • 3 Leadbeater N, Marco M. J. Org. Chem. 2003; 68: 888
    Crossref
  • 4 Itoh T, Mase T. J. Org. Chem. 2006; 71: 2203
    Crossref
  • 5 A total of 27 conditions were evaluated: catalysts: PdCl2, Pd(OAc)2, and Pd(PPh3)4; bases: CsF, K3PO4, and Na2CO3; solvents: H2O, THF, and toluene–EtOH–H2O (1:1:1).
  • 6 General Procedure for the SM Coupling of Sulfur-Substituted Methylphenylboronic Esters Using Conditions A: 2-[(4′-Nitrobiphenyl-4-yl)methylthio]pyrimidine (3a) 1a (164 mg, 0.5 mmol,), 2a (111 mg, 0.55 mmol), CsF (228 mg, 1.5 mmol), Pd(PPh3)4 (29 mg, 0.025 mmol), and THF (2 mL) were placed in a sealed microwave vial and stirred under microwave irradiation (maximum power 300 W) at 130 °C for 10 min. The mixture was cooled to r.t., diluted with EtOAc (20 mL) and H2O (10 mL), and extracted with EtOAc. The organic layer was washed with a sat. NaCl solution, dried over anhyd MgSO4, filtered, and concentrated under reduced pressure to give 269 mg of an orange solid. The crude product was purified by chromatography on silica gel (hexane–EtOAc, 8:2) to give 147 mg of the expected product as a yellow solid in 91% yield. 1H NMR (400 MHz, CDCl3): δ = 8.55 (d, 2 H, J = 4.8 Hz), 8.29 (d, 2 H, J = 8.8 Hz), 7.72 (d, 2 H, J = 8.8 Hz), 7.57 (m, 4 H), 6.70 (dd, 1 H, J 1 and 2 = 4.8 Hz), 4.47 (s, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 171.9, 157.3 (2 C), 147.2, 147.1, 138.8, 137.6, 129.9 (2 C), 127.7 (2 C), 127.5 (2 C), 124.1 (2 C), 116.7, 34.8 ppm. HRMS (ES): m/z calcd for [C17H13O2N3S + H]+ 324.0801; found: 324.0805. Anal. Calcd for C17H13N3O2S: C, 63.1; H, 4.1; N, 13.0. Found: C, 62.9; H, 4.1; N, 12.9. General Procedure for the SM Coupling of Sulfur-Substituted Methylphenylboronic Esters Using Conditions C: 2-[(3′-Nitrobiphenyl-4-yl)methylthio]pyrimidine (3b) 1a (125 mg, 0.38 mmol), 3-bromonitrobenzene (2b, 85 mg, 0.42 mmol), Na2CO3 (121 mg, 1.14 mmol), Pd(PPh3)4 (12 mg, 0.01 mmol), toluene (1 mL), EtOH (1 mL), and H2O (1 mL) were placed in a sealed microwave vial and stirred under microwave irradiation (maximum power 300 W) at 130 °C for 10 min. The mixture was cooled to r.t., diluted with EtOAc (20 mL) and H2O (10 mL), and extracted with EtOAc. The organic layer was washed with a sat. NaCl solution, dried over anhyd MgSO4, filtered, and concentrated under reduced pressure to give 195 mg of a brown oil. The crude product was purified by chromatography on silica gel (hexane–EtOAc, 8:2) to give 104 mg of the expected product as a yellow solid in 85% yield. 1H NMR (400 MHz, CDCl3): δ = 8.53 (d, 2 H, J = 4.8 Hz), 4.41 (m, 1 H), 8.17 (dd, 1 H, J 1 = 7.9 Hz, J 2 = 2.2 Hz), 7.87 (d, 1 H, J = 7.9 Hz), 7.62–7.52 (m, 5 H), 6.98 (dd, 1 H, J 1 and 2 = 4.8 Hz), 4.46 (s, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 171.9, 157.3 (2 C), 148.8, 142.5, 138.3, 137.5, 132.9, 129.9 (2 C), 129.7, 127.2 (2 C), 122.0, 121.8, 116.7, 34.8 ppm. HRMS (ES): m/z calcd for [C17H13O2N3S+H]+ 324.0801; found: 324.0804. Anal. Calcd for C17H13N3O2S: C, 63.1; H, 4.1; N, 13.0. Found: C, 62.9; H, 4.0; N, 13.1.
    • 7a Kozlov VA, Aleksanyan DV, Nelyubina YV, Lyssenko KA, Vasil’ev AA, Petrovskii PV, Odinets IL. Organometallics 2010; 29: 2054 ; and references cited therein
      Crossref
    • 7b The Chemistry of Pincer Compounds . 1st ed. Morales-Morales D, Jensen CM. Elsevier; Amsterdam/Oxford: 2007
      Google Scholar
    • 8a Spencer, J.; Baltus, C. B.; Press, N. J. unpublished results.
    • 8b Baltus CB. PhD Thesis. University of Greenwich; UK: 2011
      Google Scholar