Science China Chemistry

, Volume 59, Issue 2, pp 180–183 | Cite as

Photoredox-catalyzed [4+2] annulation of cyclobutylanilines with alkenes, alkynes, and diynes in continuous flow

  • Jiang Wang
  • Theresa H. Nguyen
  • Nan ZhengEmail author
Articles SPECIAL TOPIC · Organic Photochemistry


Continuous flow has recently emerged as a powerful enabling technology that greatly improves many reactions’ efficiency. Here, we apply the technology to intermolecular [4+2] annulation of cyclobutylanilines with alkenes, alkynes, and diynes by photoredox catalysis. An across-the-board improvement in the annulation’s efficiency is noticed. Moreover, a gram-scale annulation is successfully demonstrated in continuous flow using a much lower catalyst loading.


photocatalysis continuous flow N-cyclobutylaniline [4+2] annulation visible light 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Supplementary material

11426_2015_5547_MOESM1_ESM.pdf (6.1 mb)
Supplementary material, approximately 6.06 MB.


  1. 1.
    For selected approaches: a)_Ley SV, Fitzpatrick DE, Myers RM, Battilocchio C, Ingham, RJ. Angew Chem Int Ed, 2015, 54: 10122–10136CrossRefGoogle Scholar
  2. b).
    Poliakoff M, Han X. Chem Soc Rev, 2012, 41: 1428–1436CrossRefGoogle Scholar
  3. c).
    Cravotto G, Cintas P. Chem Soc Rev, 2006, 35: 180–196CrossRefGoogle Scholar
  4. 2.
    For selected recent reviews on continuous flow in organic synthesis: a)_Webb D, Jamison TF. Chem Sci, 2010, 1: 675–680CrossRefGoogle Scholar
  5. b).
    Kirschning A, Solodenko W, Mennecke K. Chem Eur J, 2006, 12: 5972–5990CrossRefGoogle Scholar
  6. c).
    Zhao DB, Ding KL. ACS Catal, 2013, 3: 928–944CrossRefGoogle Scholar
  7. d).
    Wegner J, Ceylan S, Kirschning A. Adv Synth Catal, 2012, 354: 17–57CrossRefGoogle Scholar
  8. e).
    Wiles C, Watts P. Green Chem, 2012, 14: 38–54CrossRefGoogle Scholar
  9. 3.
    For selected recent reviews on photocatalysis in flow: a)_Knowles JP, Elliott LD, Booker-Milburn KI. Beilstein J Org Chem, 2012, 8: 2025–2052CrossRefGoogle Scholar
  10. b).
    Garlets ZJ, Nguyen JD, Stephenson CRJ. Isr J Chem, 2014, 54: 351–360CrossRefGoogle Scholar
  11. c).
    Gilmore K, Seeberger PH. Chem Rec, 2014, 14: 410–418CrossRefGoogle Scholar
  12. 4.
    Braun AM, Jakob L, Oliveros E, do Nascimento CAO. Up-scaling photochemical reactions. In: Volman DH, Hammond GS, Neckers DC, Eds. Advances in photochemistry. Volume 18. Hoboken: John Wiley & Sons, 2007. 235–314Google Scholar
  13. 5.
    a)_Su YH, Straathof NJW, Hessel V, Noël T. Chem Eur J, 2014, 20: 10562–10589CrossRefGoogle Scholar
  14. b).
    Wegner J, Ceylan S, Kirschning A. Chem Commun, 2011, 47: 4583–4592CrossRefGoogle Scholar
  15. 6.
    For selected recent examples: a)_Tucker JW, Zhang Y, Jamison TF, Stephenson CRJ. Angew Chem Int Ed, 2012, 51: 4144–4147CrossRefGoogle Scholar
  16. b).
    Nguyen J, Reiss B, Dai CH, Stephenson CRJ. Chem Commun, 2013, 49: 4352–4354CrossRefGoogle Scholar
  17. c).
    Straathof NJW, Gemoets HPL, Wang X, Schouten JC, Hessel V, Noël T. Chem Sus Chem, 2014, 7: 1612–1617CrossRefGoogle Scholar
  18. d).
    Cantillo D, Frutos O, Rincon JA, Mateos C, Kappe CO. Org Lett, 2014, 16: 896–899CrossRefGoogle Scholar
  19. e).
    Wang X, Cuny GD, Noël T. Angew Chem Int Ed, 2013, 52: 7860–7864CrossRefGoogle Scholar
  20. f).
    Rueping M, Vila C, Bootwicha T. ACS Catal, 2013, 3: 1676–1680CrossRefGoogle Scholar
  21. g).
    Hernandez-Perez AC, Collins SK. Angew Chem Int Ed, 2013, 52: 12696–12700CrossRefGoogle Scholar
  22. h).
    Bou-Hamdan F, Seeberger PH. Chem Sci, 2012, 3: 1612–1616CrossRefGoogle Scholar
  23. 7.
    Elliott LD, Knowles JP, Koovits PJ, Maskill KG, Ralph MJ, Lejeune G, Edwards LJ, Robinson RI, Clemens IR, Cox B, Pascoe DD, Koch G, Eberle M, Berry MB, Booker-Milburn KI. Chem Eur J, 2014, 20: 15226–15232CrossRefGoogle Scholar
  24. 8.
    Wang J, Zheng N. Angew Chem Int Ed, 2015, 54: 11424–11427CrossRefGoogle Scholar
  25. 9.
    For selected examples of the cyclobutyl ring opening via single electron oxidation process: a)_Meyer K, Rocek J. J Am Chem Soc, 1972, 94: 1209–1214CrossRefGoogle Scholar
  26. b).
    Tsunoi S, Ryu I, Tamura Y, Yamasaki S, Sonoda N. Synlett, 1994: 1009–1011Google Scholar
  27. c).
    Casey BM, Eakin CA, Flowers II RA. Tetrahedron Lett, 2009, 50: 1264–1266CrossRefGoogle Scholar
  28. d).
    Zhao HJ, Fan XF, Yu JJ, Zhu C. J Am Chem Soc, 2015, 137: 3490–3493CrossRefGoogle Scholar
  29. e).
    Ren RG, Zhao HJ, Huang LT, Zhu C. Angew Chem Int Ed, 2015, 54: 12692–12696CrossRefGoogle Scholar
  30. f).
    Yu JJ, Zhao HJ, Liang SG, Bao XG, Zhu C. Org Biomol Chem, 2015, 13: 7924–7927CrossRefGoogle Scholar
  31. 10.
    Maity S, Zhu MZ, Shinabery RS, Zheng N. Angew Chem Int Ed, 2012, 51: 222–226CrossRefGoogle Scholar
  32. 11.
    Nguyen TN, Morris SA, Zheng N. Adv Synth Catal, 2014, 356: 2831–2837CrossRefGoogle Scholar
  33. 12.
    Proposed distonic iminium ion: Open image in new window Google Scholar

Copyright information

© Science China Press and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Department of Chemistry and BiochemistryUniversity of ArkansasFayettevilleUSA

Personalised recommendations