Skip to main content

Thank you for visiting 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.

Photoredox activation of carbon dioxide for amino acid synthesis in continuous flow


Although carbon dioxide (CO2) is highly abundant, its low reactivity has limited its use in chemical synthesis. In particular, methods for carbon–carbon bond formation generally rely on two-electron mechanisms for CO2 activation and require highly activated reaction partners. Alternatively, radical pathways accessed via photoredox catalysis could provide new reactivity under milder conditions. Here we demonstrate the direct coupling of CO2 and amines via the single-electron reduction of CO2 for the photoredox-catalysed continuous flow synthesis of α-amino acids. By leveraging the advantages of utilizing gases and photochemistry in flow, a commercially available organic photoredox catalyst effects the selective α-carboxylation of amines that bear various functional groups and heterocycles. The preliminary mechanistic studies support CO2 activation and carbon–carbon bond formation via single-electron pathways, and we expect that this strategy will inspire new perspectives on using this feedstock chemical in organic synthesis.

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

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it


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

Figure 1: Design plan for α-carboxylation of amines with CO2.
Figure 2: Expanding the scope of the α-carboxylation protocol.
Figure 3: Proposed mechanism for the photoredox-catalysed α-carboxylation of amines with CO2.


  1. Arakawa, H. et al. Catalysis research of relevance to carbon management: progress, challenges, and opportunities. Chem. Rev. 101, 953–996 (2001).

    Article  CAS  Google Scholar 

  2. Appel, A. M. et al. Frontiers, opportunities, and challenges in biochemical and chemical catalysis of CO2 fixation. Chem. Rev. 113, 6621–6658 (2013).

    Article  CAS  Google Scholar 

  3. Liu, Q., Wu, L., Jackstell, R. & Beller, M. Using carbon dioxide as a building block in organic synthesis. Nat. Commun. 6, 5933 (2015).

    Article  Google Scholar 

  4. Sakakura, T., Choi, J.-C. & Yasuda, H. Transformation of carbon dioxide. Chem. Rev. 107, 2365–2387 (2007).

    Article  CAS  Google Scholar 

  5. Aresta, M. in Activation of Small Molecules: Organometallic and Bioinorganic Perspectives (ed. Tolman, W. B.) 1–41 (Wiley-VCH, 2006).

    Book  Google Scholar 

  6. Omae, I. Recent developments in carbon dioxide utilization for the production of organic chemicals. Coord. Chem. Rev. 256, 1384–1405 (2012).

    Article  CAS  Google Scholar 

  7. Wu, J. et al. Continuous flow synthesis of ketones from carbon dioxide and organolithium or Grignard reagents. Angew. Chem. Int. Ed. 53, 8416–8420 (2014).

    Article  CAS  Google Scholar 

  8. Jones, J. Amino Acid and Peptide Synthesis (Oxford Univ. Press, 2002).

    Google Scholar 

  9. Otero, M. D., Batanero, B. & Barba, F. CO2 anion–radical in organic carboxylations. Tetrahedron Lett. 47, 2171–2173 (2006).

    Article  CAS  Google Scholar 

  10. Morgenstern, D. A., Wittrig, R. E., Fanwick, P. E. & Kubiak, C. P. Photoreduction of carbon dioxide to its radical anion by nickel cluster [Ni3(μ3-I)2(dppm)3]: formation of two carbon–carbon bonds via addition of carbon dioxide radical anion to cyclohexene. J. Am. Chem. Soc. 115, 6470–6471 (1993).

    Article  CAS  Google Scholar 

  11. Fagnoni, M., Dondi, D., Ravelli, D. & Albini, A. Photocatalysis for the formation of the C−C bond. Chem. Rev. 107, 2725–2756 (2007).

    Article  CAS  Google Scholar 

  12. Prier, C. K., Rankic, D. A. & MacMillan, D. W. C. Visible light photoredox catalysis with transition metal complexes: applications in organic synthesis. Chem. Rev. 113, 5322–5363 (2013).

    Article  CAS  Google Scholar 

  13. Nicewicz, D. A. & Nguyen, T. M. Recent applications of organic dyes as photoredox catalysts in organic synthesis. ACS Catal. 4, 355–360 (2014).

    Article  CAS  Google Scholar 

  14. Schultz, D. M. & Yoon, T. P. Solar synthesis: prospects in visible light photocatalysis. Science 343, 1239176 (2014).

    Article  Google Scholar 

  15. Beatty, J. W. & Stephenson, C. R. J. Amine functionalization via oxidative photoredox catalysis: methodology development and complex molecule synthesis. Acc. Chem. Res. 48, 1474–1484 (2015).

    Article  CAS  Google Scholar 

  16. Zuo, Z. et al. Merging photoredox with nickel catalysis: coupling of α-carboxyl sp3-carbons with aryl halides. Science 345, 437–440 (2014).

    Article  CAS  Google Scholar 

  17. Lamy, E., Nadjo, L. & Saveant, J. M. Standard potential and kinetic parameters of the electrochemical reduction of carbon dioxide in dimethylformamide. J. Electroanal. Chem. Interfacial Electrochem. 78, 403–407 (1977).

    Article  CAS  Google Scholar 

  18. Fujita, E. & Brunschwig, B. S. in Electron Transfer in Chemistry (ed. Balzani, V.) 88–126 (Wiley-VCH, 2001).

    Book  Google Scholar 

  19. Matsuoka, S. et al. Photocatalysis of oligo(p-phenylenes): photochemical reduction of carbon dioxide with triethylamine. J. Phys. Chem. 96, 4437–4442 (1992).

    Article  CAS  Google Scholar 

  20. McQuade, D. T. & Seeberger, P. H. Applying flow chemistry: methods, materials, and multistep synthesis. J. Org. Chem. 78, 6384–6389 (2013).

    Article  CAS  Google Scholar 

  21. Ley, S. V., Fitzpatrick, D. E., Myers, R. M., Battilocchio, C. & Ingham, R. J. Machine-assisted organic synthesis. Angew. Chem. Int. Ed. 54, 10122–10136 (2015).

    Article  CAS  Google Scholar 

  22. Mallia, C. J. & Baxendale, I. R. The use of gases in flow synthesis. Org. Process Res. Dev. 20, 327–360 (2016).

    Article  CAS  Google Scholar 

  23. Cambié, D., Bottecchia, C., Straathof, N. J. W., Hessel, V. & Noël, T. Applications of continuous-flow photochemistry in organic synthesis, material science, and water treatment. Chem. Rev. 116, 10276–10341 (2016).

    Article  Google Scholar 

  24. McNally, A., Prier, C. K. & MacMillan, D. W. C. Discovery of an α-amino C–H arylation reaction using the strategy of accelerated serendipity. Science 334, 1114–1117 (2011).

    Article  CAS  Google Scholar 

  25. Chowdhury, F. A., Yamada, H., Higashii, T., Goto, K. & Onoda, M. CO2 capture by tertiary amine absorbents: a performance comparison study. Ind. Eng. Chem. Res. 52, 8323–8331 (2013).

    Article  CAS  Google Scholar 

  26. Telmesani, R., Park, S. H., Lynch-Colameta, T. & Beeler, A. B. [2+2] photocycloaddition of cinnamates in flow and development of a thiourea catalyst. Angew. Chem. Int. Ed. 54, 11521–11525 (2015).

    Article  CAS  Google Scholar 

  27. Singh, S. B. Total synthesis of flutimide, a novel endonuclease inhibitor of influenza virus. Tetrahedron Lett. 36, 2009–2012 (1995).

    Article  CAS  Google Scholar 

  28. Aschwanden, P., Stephenson, C. R. J. & Carreira, E. M. Highly enantioselective access to primary propargylamines: 4-piperidinone as a convenient protecting group. Org. Lett. 8, 2437–2440 (2006).

    Article  CAS  Google Scholar 

  29. Clark, J. C., Phillipps, G. H., Steer, M. R., Stephenson, L. & Cooksey, A. R. Resolution of esters of phenylglycine with (+)-tartaric acid. J. Chem. Soc. Perkin Trans. 1, 471–474 (1976).

    Article  Google Scholar 

  30. Wegman, M. A. et al. Dynamic kinetic resolution of phenylglycine esters via lipase-catalysed ammonolysis. Tetrahedron: Asymmetry 10, 1739–1750 (1999).

    Article  CAS  Google Scholar 

Download references


We thank the Novartis-MIT Center for Continuous Manufacturing for financial support and several Novartis colleagues for suggestions, in particular B. Schenkel, B. Martin, J. Sedelmeier, G. Penn, F. Venturoni and J. Haber. H.S. is grateful for a graduate fellowship from the Korean Government Scholarship Program for Study Overseas, and M.H.K. was supported by a postdoctoral fellowship from the National Institute of General Medical Sciences (F32GM108181). The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We thank A. B. Beeler for guidance in setting up the flow photochemistry system, T. M. Swager for the use of a spectrophotometer and L. Li for mass spectral data (conducted on an instrument purchased with the assistance of National Science Foundation Grant CHE-0234877).

Author information

Authors and Affiliations



H.S. and M.H.K. performed the experiments, M.H.K. and T.F.J. conceived the idea and H.S., M.H.K. and T.F.J. designed the research and wrote the manuscript: All the authors commented on the final draft of the manuscript and contributed to the analysis and interpretation of the data.

Corresponding author

Correspondence to Timothy F. Jamison.

Ethics declarations

Competing interests

T.F.J. is a cofounder of Snapdragon Chemistry, Inc., and a scientific adviser for Zaiput Flow Technologies, Continuus Pharmaceuticals, Paraza Pharmaceuticals and Asymchem.

Supplementary information

Supplementary information

Supplementary information (PDF 6555 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Seo, H., Katcher, M. & Jamison, T. Photoredox activation of carbon dioxide for amino acid synthesis in continuous flow. Nature Chem 9, 453–456 (2017).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


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