Synlett 2018; 29(06): 799-804
DOI: 10.1055/s-0036-1591523
letter
© Georg Thieme Verlag Stuttgart · New York

(DPEPhos)Ni(mesityl)Br: An Air-Stable Pre-Catalyst for Challenging Suzuki–Miyaura Cross-Couplings Leading to Unsymmetrical Biheteroaryls

Ryan S. Sawatzky
Department of Chemistry, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada   Email: mark.stradiotto@dal.ca
,
Department of Chemistry, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada   Email: mark.stradiotto@dal.ca
› Author Affiliations
We are grateful to the Natural Sciences and Engineering Research Council of Canada (Discovery Grant RGPIN-2014-04807 and I2I Grant I2IPJ/485197-2015) and Dalhousie University for their support of this work.
Further Information

Publication History

Received: 30 October 2017

Accepted after revision: 23 November 2017

Publication Date:
02 January 2018 (online)


Abstract

The successful application of (DPEPhos)Ni(mesityl)Br (C1) as a pre-catalyst in the Suzuki–Miyaura cross-coupling of heteroaryl chlorides or bromides and heteroaryl boronic acids is reported. The use of C1 in this context allows for such reactions to be conducted under mild conditions (2 mol% Ni, 25 °C), including cross-couplings leading to unsymmetrical biheteroaryls. Successful transformations of this type involving problematic pyridinyl boronic acid substrates (10 mol% Ni, 60 °C) are also described.

Supporting Information

 
  • References and Notes

    • 1a Miyaura N. Suzuki A. Chem. Rev. 1995; 95: 2457
    • 1b Phan NT. S. Van Der Sluys M. Jones CW. Adv. Synth. Catal. 2006; 348: 609
    • 1c Martin R. Buchwald SL. Acc. Chem. Res. 2008; 41: 1461
    • 1d Torborg C. Beller M. Adv. Synth. Catal. 2009; 351: 3027
    • 1e Molander GA. Canturk B. Angew. Chem. Int. Ed. 2009; 48: 9240
    • 1f Slagt VF. de Vries AH. M. de Vries JG. Kellogg RM. Org. Process Res. Dev. 2010; 14: 30
    • 1g Roughley SD. Jordan AM. J. Med. Chem. 2011; 54: 3451
    • 1h Seechurn CC. C. J. Kitching MO. Colacot TJ. Snieckus V. Angew. Chem. Int. Ed. 2012; 51: 5062
    • 1i Valente C. Çalimsiz S. Hoi KH. Mallik D. Sayah M. Organ MG. Angew. Chem. Int. Ed. 2012; 51: 3314
    • 1j Lennox AJ. J. Lloyd-Jones GC. Chem. Soc. Rev. 2014; 43: 412
    • 1k Guram AS. Org. Process Res. Dev. 2016; 20: 1754
  • 2 Suzuki A. Angew. Chem. Int. Ed. 2011; 50: 6722
  • 3 For the application of palladium-catalyzed Suzuki–Miyaura cross-coupling in the assembly of biheteroaryl compounds for use in treating chronic hepatitis C virus infection, see: Beaulieu PL. Bos M. Cordingley MG. Chabot C. Fazal G. Garneau M. Gillard JR. Jolicoeur E. LaPlante S. McKercher G. Poirier M. Poupart MA. Tsantrizos YS. Duan JM. Kukolj G. J. Med. Chem. 2012; 55: 7650
  • 4 For a recent in-depth study, see: Cox PA. Leach AG. Campbell AD. Lloyd-Jones G. C. J. Am. Chem. Soc. 2016; 138: 9145
  • 5 Han F.-S. Chem. Soc. Rev. 2013; 42: 5270

    • For some prominent representative examples, see:
    • 6a Guan B.-T. Wang Y. Li B.-J. Yu D.-G. Shi Z.-J. J. Am. Chem. Soc. 2008; 130: 14468
    • 6b Quasdorf KW. Tian X. Garg NK. J. Am. Chem. Soc. 2008; 130: 14422
    • 6c Yu D.-G. Yu M. Guan B.-T. Li B.-J. Zheng Y. Wu Z.-H. Shi Z.-J. Org. Lett. 2009; 11: 3374
    • 6d Quasdorf KW. Riener M. Petrova KV. Garg NK. J. Am. Chem. Soc. 2009; 131: 17748
    • 6e Quasdorf KW. Antoft-Finch A. Liu P. Silberstein AL. Komaromi A. Blackburn T. Ramgren SD. Houk KN. Snieckus V. Garg NK. J. Am. Chem. Soc. 2011; 133: 6352
    • 6f Leowanawat P. Zhang N. Percec V. J. Org. Chem. 2012; 77: 1018
    • 6g Leowanawat P. Zhang N. Safi M. Hoffman DJ. Fryberger MC. George A. Percec V. J. Org. Chem. 2012; 77: 2885
    • 6h Chen Q. Fan X.-H. Zhang L.-P. Yang L.-M. RSC Adv. 2014; 4: 53885
    • 6i Chen X. Ke H. Zou G. ACS Catal. 2014; 4: 379
    • 6j Handa S. Slack ED. Lipshutz BH. Angew. Chem. Int. Ed. 2015; 54: 11994
    • 6k Guo L. Liu X. Baumann C. Rueping M. Angew. Chem. Int. Ed. 2016; 55: 15415
    • 6l Malineni J. Jezorek RL. Zhang N. Percec V. Synthesis 2016; 48: 2795
    • 6m Weires NA. Baker EL. Garg NK. Nat. Chem. 2016; 8: 75
  • 7 Ge S. Hartwig JF. Angew. Chem. Int. Ed. 2012; 51: 12837
  • 8 For a recent review documenting the benefits of employing L n NiCl(o-tolyl) and related pre-catalysts in nickel cross-couplings, see: Hazari N. Melvin PR. Beromi MM. Nat. Rev. Chem. 2017; 1: 0025
  • 9 Guard LM. Mohadjer Beromi M. Brudvig GW. Hazari N. Vinyard DJ. Angew. Chem. Int. Ed. 2015; 54: 13352
  • 10 For the in situ generation of (DPPF)Ni(o-tolyl)Cl from (TMEDA)Ni(o-tolyl)Cl and DPPF, as employed in the successful SM cross-coupling of 3-chloropyridine and 3-furanyl boronic acid, see: Shields JD. Gray EE. Doyle AG. Org. Lett. 2015; 17: 2166
  • 11 Park NH. Teverovskiy G. Buchwald SL. Org. Lett. 2014; 16: 220
  • 12 Ramgren SD. Hie L. Ye Y. Garg NK. Org. Lett. 2013; 15: 3950
  • 13 The successful cross-coupling of a quinoline-derived sulfamate and 2-methoxy-3-pyridinyl-boronic acid was disclosed in ref. 6e.
  • 14 Ando S. Matsunaga H. Ishizuka T. J. Org. Chem. 2017; 82: 1266
  • 15 Sawatzky RS. Ferguson MJ. Stradiotto M. Synlett 2017; 28: 1586
    • 16a Carrow BP. Hartwig JF. J. Am. Chem. Soc. 2011; 133: 2116
    • 16b Christian AH. Müller P. Monfette S. Organometallics 2014; 33: 2134
  • 17 Lavoie CM. MacQueen PM. Rotta-Loria NL. Sawatzky RS. Borzenko A. Chisholm AJ. Hargreaves BK. V. McDonald R. Ferguson MJ. Stradiotto M. Nat. Commun. 2016; 7: 11073
  • 18 Standley EA. Smith SJ. Muller P. Jamison TF. Organometallics 2014; 33: 2012
  • 19 Basch CH. Liao J. Xu J. Piane JJ. Watson MP. J. Am. Chem. Soc. 2017; 139: 5313
  • 20 General Procedure for Cross-coupling (GP1) Unless otherwise specified, under an inert atmosphere C1 (12.7 mg, 0.016 mmol, 2 mol %), aryl halide (0.8 mmol), boronic acid (1.6 mmol), and K3PO4 (679 mg, 3.2 mmol) were added to an oven-dried 4 dram vial containing a magnetic stir bar. 1,4-Dioxane (1.3 mL) and benzene (700 μL) were added, the vial was sealed with a screwcap featuring a PTFE/silicone septum and was removed from the glovebox. Degassed water (86 μL) was added via a gas-tight syringe. The reaction mixture was magnetically stirred for 16 h at room temperature. Note: On several occasions the base became clumpy and stuck to the bottom of the reaction vial; in these cases it was noted that reactions were more successful if efficient stirring was maintained. After 16 h, the reaction mixture was taken up in EtOAc (ca. 10 mL) and extracted with distilled water (3 × 10 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated with the aid of a rotary evaporator.
  • 21 General Procedure for Cross-Coupling Using Pyridinyl Boronic Acids (GP2) Unless otherwise specified, under an inert atmosphere C1 (31.9 mg, 0.04 mmol, 10 mol %), aryl halide (0.4 mmol), boronic acid (1.2 mmol), and KOtBu (157.1 mg, 1.4 mmol), were added to an oven-dried 4 dram vial containing a magnetic stir bar. 1,4-Dioxane (4 mL) and EtOH (101.7 μL) were added. The vial was sealed with a screwcap featuring a PTFE/silicone septum and was removed from the glovebox. The reaction mixture was magnetically stirred for 16 h in a temperature-controlled aluminum heating block set to 60 °C. After 16 h, the reaction mixture was cooled to room temperature, taken up in EtOAc (ca. 10 mL), and extracted with distilled water (3 × 10 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated with the aid of a rotary evaporator.
  • 22 Representative Synthesis A: Preparation of 2b Following GP1 (aryl halide 127.2 mg, boronic acid 337.6 mg), the title product was obtained via flash chromatography using silica and 30% EtOAc in hexanes. The product was isolated as white solid (74%). 1H NMR (500.1 MHz, CDCl3): δ = 9.15 (s, 1 H), 8.76 (s, 2 H), 7.49–7.48 (m, 1 H), 6.36–6.32 (m, 2 H), 1.46 (s, 9 H). 13C{1H} NMR (125.8 MHz, CDCl3): δ = 156.9, 156.3, 148.7, 128.6, 127.5, 124.1, 116.5, 111.2, 84.7, 27.7. HRMS (ESI+): m/z calcd for C13H15N3NaO2: 268.1056; found: 268.1067 [M + Na]+.
  • 23 Representative Synthesis B: Preparation of 3d Following GP2 (aryl halide 54.4 mg, boronic acid 249.6 mg), the title product was obtained via flash chromatography using silica and 70% EtOAc in hexanes. The product was isolated as a white solid (88%). 1H NMR (300.1 MHz, CDCl3): δ = 9.16 (d, J = 2.2 Hz, 1 H), 8.61 (d, J = 2.4 Hz, 1 H), 8.25 (d, J = 2.1 Hz, 1 H), 8.15 (d, J = 8.4 Hz, 1 H), 7.91–7.89 (m, 2 H), 7.75–7.72 (m, 1 H), 7.62–7.59 (m, 1 H), 6.81 (d, J = 8.8 Hz, 1 H), 3.89 (t, J = 4.7 Hz, 4 H), 3.64 (t, J = 5.0 Hz, 4 H). 13C{1H} NMR (125.8 MHz, CDCl3): δ = 159.0, 149.2, 147.1, 146.5, 136.2, 131.7, 131.1, 129.2, 129.1, 128.1, 127.7, 127.0, 123.3, 106.8, 66.7, 45.5; HRMS (ESI+): m/z calcd for C18H18N3O: 292.1444; found: 292.1443 [M + H]+.