Synlett 2019; 30(14): 1607-1614
DOI: 10.1055/s-0037-1611527
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© Georg Thieme Verlag Stuttgart · New York

Intermolecular Reactions of Pyridyl Radicals with Olefins via Photoredox Catalysis

Ciaran P. Seath
,
Nathan T. Jui*
Department of Chemistry, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA   Email: njui@emory.edu
› Author Affiliations
Financial support for this work was provided by startup funds from Emory University and the National Institutes of Health (GM129495).
Further Information

Publication History

Received: 01 March 2019

Accepted after revision: 04 April 2019

Publication Date:
24 April 2019 (online)

Abstract

Pyridines are valuable motifs in a number of bioactive and functional molecules. The chemoselective functionalization of these structures from stable and widely available starting materials is a meaningful goal. We have demonstrated selective formation of pyridyl radicals at any position (2-, 3-, 4-pyridyl), through the action of a reducing photoredox catalyst. These radicals readily engage alkenes to deliver high-value products. Alteration of the reaction medium has enabled the use of a diverse range of alkene subtypes in a highly divergent and chemoselective manner.

1 Introduction

2 Minisci-Type Pyridine Alkylation

3 An Alternate Approach – Reductive Radical Formation

4 Conjugate Addition of Pyridyl Radicals

5 Radical Hydroarylation of Neutral and Rich Olefins

6 Solvent-Based Chemoselectivity

7 Summary and Outlook

 
  • References

  • 2 Vitaku E, Smith DT, Njardarson JT. J. Med. Chem. 2014; 57: 10257
  • 3 Almond-Thynne J, Blakemore DC, Pryde DC, Spivey AC. Chem. Sci. 2017; 8: 40
  • 4 Zhao S, Gensch T, Murray B, Niemeyer ZL, Sigman MS, Biscoe MR. Science 2018; 362: 670
    • 5a Smith JM, Harwood SJ, Baran PS. Acc. Chem. Res. 2018; 51: 1807
    • 5b Yan M, Lo JC, Edwards JT, Baran PS. J. Am. Chem. Soc. 2016; 138: 12692
  • 6 Minisci F, Galli B, Cecere M, Malatesta V, Caronna T. Tetrahedron Lett. 1968; 54: 5609
  • 7 Minisci F, Bernardi R, Bertini F, Galli R, Perchinummo M. Tetrahedron 1971; 27: 3575
  • 8 Minisci F, Vismara E, Fontana F, Morini G, Serravalle M, Giordano C. J. Org. Chem. 1986; 51: 4411
  • 9 Molander GA, Colombel V, Braz VA. Org. Lett. 2011; 13: 1852
  • 10 Barton DH. R, Garcia B, Togo H, Zard SZ. Tetrahedron Lett. 1986; 27: 1327
  • 11 Coppa F, Fontaria F, Minisci F, Pianese G, Tortoreto P, Zhao L. Tetrahedron Lett. 1992; 33: 687
  • 12 Seiple IB, Su S, Rodriguez RA, Gianatassio R, Fujiwara Y, Sobel AL, Baran PS. J. Am. Chem. Soc. 2010; 132: 13194
  • 13 Nagib DA, MacMillan DW. C. Nature 2011; 480: 224
  • 14 Fujiwara Y, Dixon JA, O’Hara F, Funder ED, Dixon DD, Rodriguez RA, Baxter RD, Herlé B, Sach N, Collins MR, Ishihara Y, Baran PS. Nature 2012; 492: 95
  • 15 DiRocco DA, Dykstra K, Krska S, Vachal P, Conway DV, Tudge M. Angew. Chem. Int. Ed. 2014; 53: 4802
  • 16 Hari DP, König B. Angew. Chem. Int. Ed. 2013; 52: 4734
  • 17 Shankaran K, Sloan CP, Snieckus V. Tetrahedron Lett. 1985; 26: 6001
  • 18 Garden SJ, Avila DV, Beckwith AL. J, Bowry VW, Ingold KU, Lusztyk J. J. Org. Chem. 1996; 61: 805
  • 19 Birch AJ. J. Chem. Soc. 1944; 430
  • 20 Nguyen JD, D'Amato EM, Narayanam JM. R, Stephenson CR. J. Nat. Chem. 2012; 4: 854
  • 21 Discekici EH, Treat NJ, Poelma SO, Mattson KM, Hudson ZM, Luo Y, Hawker CJ, de Alaniz JR. Chem. Commun. 2015; 51: 11705
    • 22a Senaweera S, Weaver JD. J. Am. Chem. Soc. 2016; 138: 2520
    • 22b Arora A, Weaver JD. Org. Lett. 2016; 18: 3996
    • 22c Singh A, Fennell CJ, Weaver JD. Chem. Sci. 2016; 7: 6796
    • 22d Singh A, Kubik JJ, Weaver JD. Chem. Sci. 2015; 6: 7206
    • 22e Arora A, Teegardin KA, Weaver JD. Org. Lett. 2015; 17: 3722
    • 23a Ghosh I, König B. Angew. Chem. Int. Ed. 2016; 55: 7676
    • 23b Marzo L, Ghosh I, König B. ACS Catal. 2016; 6: 6780
    • 23c Ghosh I, Ghosh T, Bardagi JI, König B. Science 2014; 346: 725
  • 24 Aycock RA, Wang H, Jui NT. Chem. Sci. 2017; 8: 3121
  • 25 Aycock RA, Vogt DB, Jui NT. Chem. Sci. 2017; 8: 7998
  • 26 Karady S, Amato S, Weinstock M. Tetrahedron Lett. 1984; 25: 4337
  • 27 Boyington AJ, Riu M.-LY, Jui NT. J. Am. Chem. Soc. 2017; 139: 6582
  • 28 Jana R, Pathak TP, Sigman MS. Chem. Rev. 2011; 111: 1417
  • 29 Seath CP, Vogt DB, Xu Z, Boyington AJ, Jui NT. J. Am. Chem. Soc. 2018; 140: 15525
  • 30 Campbell JM, Xu H.-C, Moeller KD. J. Am. Chem. Soc. 2012; 134: 18338
  • 31 Bégué J.-P, Bonnet-Delpon D, Crousse B. Synlett 2004; 18