Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Comment
  • Published:

Radical coupling from alkyl amines

Radical intermediates are key species in many chemical transformations. Recent advances have provided a new suite of selective radical alkylation reactions. This Comment highlights pioneering studies using alkyl amines that act as radical precursors in a number of catalytic processes by their conversion to alkylpyridinium salts.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Precursors for radical intermediates.
Fig. 2: Ni-catalysed cross-coupling of amine-derived electrophiles.
Fig. 3: Ni-catalysed cross-coupling couplings of alkyl pyridinium salts.
Fig. 4: Photoredox catalysed deaminative radical alkylations.
Fig. 5: Mechanistic aspects of photoredox-catalysed activation of N-alkyl pyridiniums salts.
Fig. 6

References

  1. Beller, M., Renken, A. & van Santen, R. A. Catalysis from Principles to Application (Wiley-VCH, Hoboken, 2012).

  2. Blakemore, D. C. et al. Nat. Chem. 10, 383–394 (2018).

    Article  CAS  Google Scholar 

  3. Yan, M., Lo, J. C., Edwards, J. T. & Baran, P. S. J. Am. Chem. Soc. 138, 12692–12714 (2016).

    Article  CAS  Google Scholar 

  4. Choi, J. & Fu, G. C. Science 356, 9 (2017).

    Article  Google Scholar 

  5. Lovering, F. MedChemComm 4, 515–519 (2013).

    Article  CAS  Google Scholar 

  6. Matyjaszewski, K. & Tsarevsky, N. V. J. Am. Chem. Soc. 136, 6513–6533 (2014).

    Article  CAS  Google Scholar 

  7. Wu, X. Y. et al. J. Am. Chem. Soc. 140, 14836–14843 (2018).

    Article  CAS  Google Scholar 

  8. Shaw, M. H., Twilton, J. & MacMillan, D. W. C. J. Org. Chem. 81, 6898–6926 (2016).

    Article  CAS  Google Scholar 

  9. Twilton, J. et al. Nat. Rev. Chem. 1, 19 (2017).

    Article  Google Scholar 

  10. Cornella, J. et al. J. Am. Chem. Soc. 138, 2174–2177 (2016).

    Article  CAS  Google Scholar 

  11. Nawrat, C. C., Jamison, C. R., Slutskyy, Y., MacMillan, D. W. C. & Overman, L. E. J. Am. Chem. Soc. 137, 11270–11273 (2015).

    Article  CAS  Google Scholar 

  12. Milligan, J. A., Phelan, J. P., Badir, S. O. & Molander, G. A. Angew. Chem. Int. Ed. 58, 6152–6163 (2019).

    Article  CAS  Google Scholar 

  13. Smith, J. M., Dixon, J. A., deGruyter, J. N. & Baran, P. S. J. Med. Chem. 62, 2256–2264 (2018).

    Article  Google Scholar 

  14. Katritzky, A. R. & Marson, C. M. Angew. Chem. Int. Ed. 23, 420–429 (1984).

    Article  Google Scholar 

  15. Basch, C. H., Liao, J. N., Xu, J. Y., Piane, J. J. & Watson, M. P. J. Am. Chem. Soc. 139, 5313–5316 (2017).

    Article  CAS  Google Scholar 

  16. Liao, J. et al. Org. Lett. 20, 3030–3033 (2018).

    Article  CAS  Google Scholar 

  17. Guan, W., Liao, J. & Watson, M. P. Synthesis 50, 3231–3237 (2018).

    Article  CAS  Google Scholar 

  18. Ociepa, M., Turkowska, J. & Gryko, D. ACS Catal. 8, 11362–11367 (2018).

    Article  CAS  Google Scholar 

  19. Sandfort, F., Strieth-Kalthoff, F., Klauck, F. J. R., James, M. J. & Glorius, F. Chem. Eur. J. 24, 17210–17214 (2018).

    Article  CAS  Google Scholar 

  20. Katritzky, A. R., Deville, G. & Patel, R. C. Tetrahedron 37, 25–30 (1981).

    Article  Google Scholar 

  21. Pound, S. M. & Watson, M. P. Chem. Commun. 54, 12286–12301 (2018).

    Article  CAS  Google Scholar 

  22. Plunkett, S., Basch, C. H., Santana, S. O. & Watson, M. P. J. Am. Chem. Soc. 141, 2257–2262 (2019).

    Article  CAS  Google Scholar 

  23. Ni, S., Li, C., Han, J., Mao, Y. & Pan, Y. Ni-catalyzed deamination cross-electrophile coupling of Katritzky salts with halides via C–N bond activation. Preprint at https://go.nature.com/2K9J88M(2019).

  24. Weix, D. J. Acc. Chem. Res. 48, 1767–1775 (2015).

    Article  CAS  Google Scholar 

  25. Yue, H. et al. Chem. Sci. 10, 4430–4435 (2019).

    Article  CAS  Google Scholar 

  26. Yi, J., Badir, S. O., Kammer, L. M., Ribagorda, M. & Molander, G. A. Org. Lett. https://go.nature.com/2Wus0kG (2019).

  27. Martin-Montero, R., Yatham, V. R., Yin, H., Davies, J. & Martin, R. Org. Lett. 21, 2947–2951 (2019).

    Article  CAS  Google Scholar 

  28. Liao, J. et al. Org. Lett. 21, 2941–2946 (2019).

    Article  CAS  Google Scholar 

  29. Klauck, F. J. R., James, M. J. & Glorius, F. Angew. Chem. Int. Ed. 56, 12336–12339 (2017).

    Article  CAS  Google Scholar 

  30. Klauck, F. J. R., Yoon, H., James, M. J., Lautens, M. & Glorius, F. ACS Catal. 9, 236–241 (2019).

    Article  CAS  Google Scholar 

  31. Ruano, J. L. G., Aleman, J., Parra, A. & Marzo, L. Eur. J. Org. Chem. 2014, 1577–1588 (2014).

    Article  Google Scholar 

  32. Jiang, X., Zhang, M.-M., Xiong, W., Lu, L.-Q. & Xiao, W.-J. Angew. Chem. Int. Ed. 58, 2402–2406 (2019).

    Article  CAS  Google Scholar 

  33. Wu, J. J., He, L., Noble, A. & Aggarwal, V. K. J. Am. Chem. Soc. 140, 10700–10704 (2018).

    Article  CAS  Google Scholar 

  34. Hu, J. F., Wang, G. Q., Li, S. H. & Shi, Z. Z. Angew. Chem. Int. Ed. 57, 15227–15231 (2018).

    Article  CAS  Google Scholar 

  35. Wu, J., Grant, P. S., Li, X., Noble, A. & Aggarwal, V. K. Angew. Chem. Int. Ed. 58, 5697–5701 (2019).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rylan J. Lundgren.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kong, D., Moon, P.J. & Lundgren, R.J. Radical coupling from alkyl amines. Nat Catal 2, 473–476 (2019). https://doi.org/10.1038/s41929-019-0292-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41929-019-0292-9

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing