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

Nature Chemistry volume 9, pages 453–456 (2017)Cite this article

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Abstract

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.

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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.

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Acknowledgements

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).

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Authors and Affiliations

  1. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Hyowon Seo, Matthew H. Katcher & Timothy F. Jamison

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  1. Hyowon Seo
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Contributions

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.

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Correspondence to Timothy F. Jamison.

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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.

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Seo, H., Katcher, M. & Jamison, T. Photoredox activation of carbon dioxide for amino acid synthesis in continuous flow. Nature Chem 9, 453–456 (2017). https://doi.org/10.1038/nchem.2690

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