CC BY-ND-NC 4.0 · SynOpen 2017; 01(01): 0024-0028
DOI: 10.1055/s-0036-1588810
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Microwave-Promoted Synthesis of 4-Arylpyrimidines by Pd-Catalysed Suzuki–Miyaura Coupling of 4-Pyrimidyl Tosylates in Water

José Rodríguez-Aguilar
,
Beatriz Ordóñez
,
Matías Vidal
,
Marcos Caroli Rezende
,
Moisés Domínguez*
Supported by: Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT) (11140497)
Further Information

Publication History

Received: 08 March 2017

Accepted after revision: 09 April 2017

Publication Date:
25 April 2017 (online)


Abstract

The Suzuki–Miyaura coupling reaction of 4-pyrimidyl tosylates was investigated with aryl, heteroaryl and alkyl boronic acids. The reaction provided 4-substituted pyrimidines in good-to-excellent yields after one-hour microwave irradiation in water at 100 °C. The method constitutes a fast option for the synthesis of these heterocyclic systems.

Supporting Information

 
  • References and Notes

  • 1 Johanson Seechurn CC. Kitching MO. Colacot TJ. Snieckus V. Angew. Chem. Int. Ed. 2012; 51: 5062
  • 2 King AO. Yasuda N. In Organometallics in Process Chemistry . Springer-Verlag; Berlin/Heidelberg: 2004: 205-245
  • 3 Arsenyan P. Paegle E. Belyakov S. Tetrahedron Lett. 2010; 51: 205
  • 4 Liu Z. Li S. Li D. He X. Hu Y. Tetrahedron 2007; 63: 1931
    • 5a Prakash GK. S. Mathew T. Hoole D. Esteves PM. Wang Q. Rasul G. Olah GA. J. Am. Chem. Soc. 2004; 126: 15770
    • 5b Qiu D. Mo F. Zheng Z. Zhang Y. Wang J. Org. Lett. 2010; 12: 5474
  • 6 Smith K. Butters W. Paget E. Goubet D. Fromentin E. Nay B. Green Chem. 1999; 1: 83
  • 7 Niu F. Zhang H. Yang H. Fu H. Synlett 2014; 25: 995

    • Accessible 4-chloropyrimidines are good coupling partners in Suzuki–Miyaura reactions, see:
    • 8a Achelle S. Ramondenc Y. Marsais F. Plé N. Eur. J. Org. Chem. 2008; 3129
    • 8b Lee D.-H. Choi M. Yu B.-W. Ryoo R. Taher A. Hossain S. Jin M.-J. Adv. Synth. Catal. 2009; 351: 2912
    • 8c Lee D.-H. Jung J.-Y. Jin M.-J. Green Chem. 2010; 12: 2024
    • 8d Anderson SC. Handy ST. Synthesis 2010; 2721
    • 10a Murphy JM. Liao X. Hartwig JF. J. Am. Chem. Soc. 2007; 129: 15434
    • 10b Imazaki Y. Shirakawa E. Ueno R. Hayashi T. J. Am. Chem. Soc. 2012; 134: 14760
    • 10c Pan J. Wang X. Zhang Y. Buchwald SL. Org. Lett. 2011; 13: 4974
    • 10d Du B. Sun JP. J. Org. Chem. 2013; 78: 2786
    • 11a Shu C. Sidhu K. Zhang L. Wang X. Krishnamurthy D. Senanayake CH. J. Org. Chem. 2010; 75: 6677
    • 11b Lee D. Ryu T. Park Y. Lee PH. Org. Lett. 2014; 16: 1144
    • 12a Domínguez M. Reissig H.-U. Synthesis 2014; 46: 1110
    • 12b Hommes P. Reissig H.-U. Eur. J. Org. Chem. 2016; 338
    • 13a Ke H. Chen X. Zou G. J. Org. Chem. 2014; 79: 7132
    • 13b Molinaro C. Scott JP. Shevlin M. Wise C. Ménard A. Gibb A. Junker EM. Lieberman D. J. Am. Chem. Soc. 2015; 137: 999
  • 14 Gøgsig TM. Lindhardt AT. Dekhane M. Grouleff J. Skrydstrup T. Chem. Eur. J. 2009; 15: 5950
    • 15a Bartrum HE. Blakemore DC. Moody CJ. Hayes CJ. J. Org. Chem. 2010; 75: 8674
    • 15b Yang J. Liu S. Zheng J.-F. Zhou J. Eur. J. Org. Chem. 2012; 6248
  • 16 Vidal M. García-Arriagada M. Rezende MC. Domínguez M. Synthesis 2016; 48: 4246
    • 17a Littke AF. Dai CY. Fu GC. J. Am. Chem. Soc. 2000; 122: 4020
    • 17b Wolfe JP. Singer RA. Yang BH. Buchwald SL. J. Am. Chem. Soc. 1999; 121: 9550
  • 18 Proutiere F. Schoenebeck F. Angew. Chem. Int. Ed. 2011; 50: 8192
    • 19a Adrio LA. Nguyen BN. Guilera G. Livingston AG. Hii KK. Catal. Sci. Technol. 2012; 2: 316
    • 19b Bedford RB. Bowen JG. Davidson RB. Haddow MF. Seymour-Julen AE. Sparkes HA. Webster R. Angew. Chem. Int. Ed. 2015; 54: 6591
    • 19c Li Z. Gelbaum C. Heaner IV WL. Fisk J. Jaganathan A. Holden B. Pollet P. Liotta C. Org. Process Res. Dev. 2016; 20: 1489

      For overlooks and reviews on various organic reactions carried out in water, see:
    • 20a Narayan S. Muldoon J. Finn MG. Fokin VV. Hartmuth CK. Sharpless KB. Angew. Chem. Int. Ed. 2005; 44: 3275
    • 20b Li C.-J. Chen L. Chem. Soc. Rev. 2006; 35: 68
    • 20c Dallinger D. Kappe CO. Chem. Rev. 2007; 107: 2563
    • 20d Chanda A. Fokin VV. Chem. Rev. 2009; 109: 725
  • 21 Berionni G. Maji B. Knochel P. Mayr H. Chem. Sci. 2012; 3: 878
  • 22 4-(4-Acetylphenyl)-6-methyl-2-phenylpyrimidine (3b)A 10-mL microwave vial was charged with 4-pyrimidyl tosylate 1a (0.588 mmol), the aryl boronic acid 2 (0.705 mmol), tetrakis(triphenylphosphine)palladium (0.029 mmol), powdered potassium carbonate (0.588 mmol) and water (5 mL). The resulting reaction mixture was irradiated for 1 h at 100 °C. The reaction mixture was then extracted three times with dichloromethane (ca. 15 mL each). The combined organic phases were dried with anhydrous sodium sulfate and filtered. The solvent was removed on a rotary evaporator and the crude product was purified by column chromatography (silica gel; n-hexane/EtOAc, 10:1) to obtain a yellow solid. Yield: 122 mg (87%); mp 148–150 °C; Rf = 0.72 (n-hexane/EtOAc, 5:1). IR (ATR): 3070, 2920, 1683, 1589, 1572 cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.61–8.52 (m, 2 H, Ph), 8.25 (d, J = 8.4 Hz, 2 H, ArH), 8.06 (d, J = 8.4 Hz, 2 H, ArH), 7.60–7.47 (m, 3 H, Ph), 7.45 (s, 1 H, H-5), 2.64 (s, 3 H, COCH3), 2.63 (s, 3 H, CH3). 13C NMR (CDCl3, 101 MHz): δ = 198.1, 168.6, 164.8, 162.7, 141.8, 138.8, 138.2, 131.1, 129.2, 128.9, 128.8, 127.8, 114.8, 27.2, 25.1. HRMS (ESI-TOF): m/z [M + H+] calcd for C19H17N2O: 289.1341; found: 289.1342.