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.

  • Article
  • Published:

Tunable catalyst-controlled syntheses of β- and γ-amino alcohols enabled by silver-catalysed nitrene transfer

Nature Catalysis volume 2, pages 899–908 (2019)Cite this article

Subjects

Abstract

Carbon–hydrogen bond functionalization methods are important tools for efficiently upgrading simple precursors to more valuable compounds. The ubiquity of amines in pharmaceuticals and natural products has led to considerable interest in strategies for the selective amidation of C–H bonds in a tunable manner. An ongoing challenge involves achieving control in situations where targeted bonds have varying bond strengths or similar steric/electronic environments. Herein, we report two complementary silver catalysts that are capable of selecting between β- or γ-C–H bonds that reside in similar steric/electronic environments, overriding a reaction at a weaker C–H bond in favour of a stronger one and activating primary C–H bonds. The mild conditions, low cost of silver, good yields and easy purification make this approach ideal for late-stage functionalizations to furnish valuable 1,2- and 1,3-aminoalcohols from easily prepared carbamate esters.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Fig. 1: Challenges in tunable site-selective C–H bond amidation.
Fig. 2: Principles guiding the design of new catalysts.
Fig. 3
Fig. 4: Steric control of site-selective C–H amidation.
Fig. 5

Similar content being viewed by others

Data availability

The data supporting the findings of this study are available within the manuscript and its Supplementary Information, or available from the author on reasonable request. Experimental details and full spectroscopic characterization data for all new compounds and copies of proton and carbon NMR spectra are provided in the Supplementary Information. The X-ray crystallographic coordinates for [(Py5Me2)AgOTf]2 in this study have previously been reported and have been deposited at the Cambridge Crystallographic Data Centre under deposition no. 1491194. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif. Furthermore, the corresponding author can be contacted directly.

References

  1. Krise, J. P. & Oliyai, R. in Biotechnology: Pharmaceutical Aspects (eds Stella, V. J. et al.) Vol. 5 (Springer, 2007).

  2. Klingler, F. D. Asymmetric hydrogenation of prochiral amino ketones to amino alcohols for pharmaceutical use. Acc. Chem. Res. 40, 1367–1376 (2007).

    Article  CAS  Google Scholar 

  3. Gallou, I. & Senanayake, C. H. Cis-1-amino-2-indanol in drug design and applications to asymmetric processes. Chem. Rev. 106, 2843–2874 (2006).

    Article  CAS  Google Scholar 

  4. Corey, E. J. & Zhang, F. re- and si-Face-selective nitroaldol reactions catalyzed by a rigid chiral quaternary ammonium salt: a highly stereoselective synthesis of the HIV protease inhibitor Amprenavir (Vertex 478). Angew. Chem. Int. Ed. 38, 1931–1934 (1999).

    Article  CAS  Google Scholar 

  5. O’Brien, P. Sharpless asymmetric aminohydroxylation: scope, limitations, and use in synthesis. Angew. Chem. Int. Ed. 38, 326–329 (1999).

    Article  Google Scholar 

  6. McGrath, N., Brichacek, M. & Njardarson, J. T. A graphical journey of innovative organic architectures that have improved our lives. J. Chem. Ed. 87, 1348–1349 (2010).

    Article  CAS  Google Scholar 

  7. Hong, S. Y. et al. Selective formation of γ-lactams via C–H amidation enabled by tailored iridium catalysts. Science 359, 1016–1021 (2018).

    Article  CAS  Google Scholar 

  8. Roizen, J. L., Harvey, M. E. & Du Bois, J. Metal-catalyzed nitrogen-atom transfer methods for the oxidation of aliphatic C–H bonds. Acc. Chem. Res. 45, 911–922 (2012).

    Article  CAS  Google Scholar 

  9. Alderson, J. M., Corbin, J. R. & Schomaker, J. M. Tunable, chemo- and site- selective nitrene transfer reactions through the rational design of silver(i) catalysts. Acc. Chem. Res. 50, 2147–2158 (2017).

    Article  CAS  Google Scholar 

  10. Che, C.-M., Le, V. K.-Y. & Zhou, C.-Y. in Comprehensive Organic Synthesis (eds Knochel, P. & Molander, G. A.) 2nd edn (Elsevier, 2014).

  11. Lu, H. & Xhang, X. P. Catalytic C–H functionalization by metalloporphyrins: recent developments and future directions. Chem. Soc. Rev. 40, 1899–1909 (2011).

    Article  CAS  Google Scholar 

  12. Díaz-Requejo, M. M. & Pérez, P. J. Coinage metal catalyzed C–H bond functionalization of hydrocarbons. Chem. Rev. 108, 3379–3394 (2008).

    Article  Google Scholar 

  13. Dequirez, G., Pons, V. & Dauban, P. Nitrene chemistry in organic synthesis: still in its infancy? Angew. Chem. Int. Ed. 51, 7384–7395 (2012).

    Article  CAS  Google Scholar 

  14. Hazelard, D., Nocquet, P.-A. & Compain, P. Catalytic C–H amination at its limits: challenges and solutions. Org. Chem. Front. 4, 2500–2521 (2017).

    Article  CAS  Google Scholar 

  15. Müller, P. & Fruit, C. Enantioselective catalytic aziridinations and asymmetric nitrene insertions into C–H bonds. Chem. Rev. 103, 2905–2920 (2003).

    Article  Google Scholar 

  16. Brandenberg, O. F., Fasan, R. & Arnold, F. H. Exploiting and engineering hemoproteins for abiological carbene and nitrene transfer reactions. Curr. Opin. Biotech. 47, 102–111 (2017).

    Article  CAS  Google Scholar 

  17. Espino, C. G. & Du Bois, J. A Rh-catalyzed C–H insertion reaction for the oxidative conversion of carbamates to oxazolidinones. Angew. Chem. Int. Ed. 40, 598–600 (2001).

    Article  CAS  Google Scholar 

  18. Espino, C. G., Wehn, P. M., Chow, J. & Du Bois, J. Synthesis of 1,3-difunctionalized amine derivatives through selective C–H bond oxidation. J. Am. Chem. Soc. 123, 6935–6936 (2001).

    Article  CAS  Google Scholar 

  19. Cui, Y. & He, C. Efficient aziridination of olefins catalyzed by a unique disilver(i) compound. J. Am. Chem. Soc. 125, 16202–16203 (2003).

    Article  CAS  Google Scholar 

  20. Cui, Y. & He, C. A silver-catalyzed intramolecular amidation of saturated C–H bonds. Angew. Chem. Int. Ed. 43, 4210–4212 (2004).

    Article  CAS  Google Scholar 

  21. Li, Z., Capretto, D. A., Rahaman, R. H. & He, C. Silver-catalyzed intermolecular amination of C–H groups. Angew. Chem. Int. Ed. 46, 5184–5186 (2007).

    Article  CAS  Google Scholar 

  22. Rigoli, J. W. et al. Chemoselective allene aziridination via Ag(i) catalysis. Org. Lett. 15, 290–293 (2013).

    Article  CAS  Google Scholar 

  23. Rigoli, J. W., Weatherly, C. D., Alderson, J. M., Vo, B. T. & Schomaker, J. M. Tunable, chemoselective amination via silver catalysis. J. Am. Chem. Soc. 135, 17238–17241 (2013).

    Article  CAS  Google Scholar 

  24. Weatherly, C. D., Alderson, J. M., Berry, J. F., Hein, J. E. & Schomaker, J. M. Catalyst-controlled nitrene transfer by tuning metal:ligand ratios: insight into the mechanisms of chemoselectivity. Organometallics 36, 1649–1661 (2017).

    Article  CAS  Google Scholar 

  25. Dolan, N. S., Scamp, R. J., Yang, T., Berry, J. F. & Schomaker, J. M. Catalyst-controlled and tunable, chemoselective silver-catalyzed intermolecular nitrene transfer: experimental and computational studies. J. Am. Chem. Soc. 138, 14658–14667 (2016).

    Article  CAS  Google Scholar 

  26. Ju, M., Weatherly, C. D., Guzei, I. A. & Schomaker, J. M. Chemo- and enantioselective silver-catalyzed aziridinations. Angew. Chem. Int. Ed. 56, 9944–9948 (2017).

    Article  CAS  Google Scholar 

  27. Scamp, R. J., Alderson, J. M., Phelps, A. M., Dolan, N. S. & Schomaker, J. M. Ligand-controlled, tunable silver-catalyzed C–H amination. J. Am. Chem. Soc. 136, 16720–16723 (2014).

    Article  Google Scholar 

  28. Scamp, R. J., Jirak, J. G., Guzei, I. A. & Schomaker, J. M. General catalyst for site-selective C(sp 3)–H bond amination of activated secondary over tertiary alkyl C(sp 3)–H bonds. Org. Lett. 18, 3014–3017 (2016).

    Article  CAS  Google Scholar 

  29. Huang, M., Yang, T., Paretsky, J., Berry, J. F. & Schomaker, J. M. Inverting steric effects: using ‘attractive’ non-covalent interactions to direct silver-catalyzed nitrene transfer. J. Am. Chem. Soc. 139, 17376–17386 (2017).

    Article  CAS  Google Scholar 

  30. Mat Lani, A. S. & Schomaker, J. M. Site-selective, catalyst-controlled alkene aziridination. Synthesis 50, 4462–4470 (2018).

    Article  CAS  Google Scholar 

  31. Alderson, J. M., Corbin, J. R. & Schomaker, J. M. Investigation of transition metal-catalyzed nitrene transfer reactions in water. Bioorg. Med. Chem. 26, 5270–5273 (2018).

    Article  CAS  Google Scholar 

  32. Padwa, A., Flick, A. C., Leverett, C. A. & Stengel, T. Rhodium(ii)-catalyzed aziridination of allyl-substituted sulfonamides and carbamates. J. Org. Chem. 69, 6377–6386 (2004).

    Article  CAS  Google Scholar 

  33. Hayes, C. J., Beavis, P. W. & Humphries, L. A. Rh(ii)-catalysed room temperature aziridination of homoallyl-carbamates. Chem. Commun. 4501–4502 (2006).

  34. Maestre, L., Sameera, W. M. C., Díaz-Requejo, M. M., Maseras, F. & Pérez, P. J. A general mechanism for the copper- and silver-catalyzed olefin aziridination reactions: concomitant involvement of the singlet and triplet pathways. J. Am. Chem. Soc. 135, 1338–1348 (2013).

    Article  CAS  Google Scholar 

  35. Fiori, K. W., Espino, C. G., Brodsky, B. H. & Du Bois, J. A mechanistic analysis of the Rh-catalyzed intramolecular C–H amination reaction. Tetrahedron 65, 3042–3051 (2009).

    Article  CAS  Google Scholar 

  36. Huang, M. et al. Synthesis, characterization and VT-NMR studies of silver(i) complexes for selective nitrene transfer. Inorg. Chem. 56, 6725–6733 (2017).

    Article  CAS  Google Scholar 

  37. Mak, C. L., Bostick, B. C., Yassin, N. M. & Campbell, M. G. Argentophilic interactions in solution: an EXAFS study of silver(i) nitrene transfer catalysts. Inorg. Chem. 57, 5720–5722 (2018).

    Article  CAS  Google Scholar 

  38. Espino, C. G., Fiori, K. W., Kim, M. & Du Bois, J. Expanding the scope of C–H amination through catalyst design. J. Am. Chem. Soc. 126, 15378–15379 (2004).

    Article  CAS  Google Scholar 

  39. Paradine, S. M. et al. A manganese catalyst for highly reactive yet chemoselective intramolecular C(sp 3)–H amination. Nat. Chem. 7, 987–994 (2015).

    Article  CAS  Google Scholar 

  40. Harvey, M. E., Musaev, D. G. & Du Bois, J. A diruthenium catalyst for selective, intramolecular allylic C–H amination: reaction development and mechanistic insight gained through experiment and theory. J. Am. Chem. Soc. 133, 17207–17216 (2011).

    Article  CAS  Google Scholar 

  41. Barman, D. N. & Nicholas, K. M. Copper-catalyzed intramolecular C–H amination. Eur. J. Org. Chem. 5, 908–911 (2011).

    Article  Google Scholar 

  42. Liang, J.-L., Yuan, S.-X., Huang, J.-S. & Che, C.-M. Intramolecular C–N bond formation reactions catalyzed by ruthenium porphyrins: amidation of sulfamate esters and aziridination of unsaturated sulfonamides. J. Org. Chem. 69, 3610–3619 (2004).

  43. Goswami, M. et al. Characterization of porphyrin-Co(iii)-‘nitrene radical’ species relevant in catalytic nitrene transfer reactions. J. Am. Chem. Soc. 137, 5468–5479 (2015).

    Article  CAS  Google Scholar 

  44. Varela-Álvarez, A. et al. Rh2(ii,iii) catalysts with chelating carboxylate and carboxamidate supports: electronic structure and nitrene transfer reactivity. J. Am. Chem. Soc. 138, 2327–2341 (2016).

    Article  Google Scholar 

  45. Charton, M. Nature of the ortho effect. II. Composition of the Taft steric parameters. J. Am. Chem. Soc. 91, 615–618 (1969).

    Article  CAS  Google Scholar 

  46. Charton, M. Steric effects. I. Esterification and acid-catalyzed hydrolysis of esters. J. Am. Chem. Soc. 97, 1552–1556 (1975).

    Article  CAS  Google Scholar 

  47. Charton, M. Steric effects. II. Base-catalyzed ester hydrolysis. J. Am. Chem. Soc. 97, 3691–3693 (1975).

    Article  CAS  Google Scholar 

  48. Charton, M. Steric effects. III. Bimolecular nucleophilic substitution. J. Am. Chem. Soc. 97, 3694–3697 (1975).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

J.M.S. is grateful to the NSF (award no. 1664374) for financial support. The following instrumentation in the Paul Bender Chemistry Instrumentation Center was supported by Thermo Q Exactive Plus by NIH 1S10 OD020022-1; Bruker Quazar APEX2 and Bruker Avance-500 by a generous gift from P. J. Bender and M. M. Bender; Bruker Avance-600 by NIH S10 OK012245; Bruker Avance-400 by NSF CHE-1048642 and the University of Wisconsin–Madison; Varian Mercury-300 by NSF CHE-0342998. C. G. Fry and H. Hofstetter at University of Wisconsin–Madison are thanked for valuable discussions about NMR equipment and techniques. M. M. Vestling of University of Wisconsin–Madison is thanked for help with mass spectrometry characterization. D. J. Weix and K. J. Garcia are thanked for access to chiral supercritical fluid chromatography instrumentation.

Author information

Author notes

  1. These authors contributed equally: Minsoo Ju, Minxue Huang.

Authors and Affiliations

  1. Department of Chemistry, University of Wisconsin–Madison, Madison, WI, USA

    Minsoo Ju, Minxue Huang, Logan E. Vine, Mahzad Dehghany, Jessica M. Roberts & Jennifer M. Schomaker

Authors
  1. Minsoo Ju
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Minxue Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Logan E. Vine
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mahzad Dehghany
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jessica M. Roberts
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jennifer M. Schomaker
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

J.M.S., M.J. and M.H. conceived the project. M.J., M.H., L.E.V. and M.D. performed the synthetic experiments. J.M.R. performed the DFT calculations. J.M.S., M.J., M.H., L.E.V. and J.M.R. wrote the manuscript.

Corresponding author

Correspondence to Jennifer M. Schomaker.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ju, M., Huang, M., Vine, L.E. et al. Tunable catalyst-controlled syntheses of β- and γ-amino alcohols enabled by silver-catalysed nitrene transfer. Nat Catal 2, 899–908 (2019). https://doi.org/10.1038/s41929-019-0339-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41929-019-0339-y

This article is cited by

Search

Advanced 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