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Photochemical single-step synthesis of β-amino acid derivatives from alkenes and (hetero)arenes


β-Amino acids are frequently found as important components in numerous biologically active molecules, drugs and natural products. In particular, they are broadly utilized in the construction of bioactive peptides and peptidomimetics, thanks to their increased metabolic stability. Despite the number of methodologies established for the preparation of β-amino acid derivatives, the majority of these methods require metal-mediated multistep manipulations of prefunctionalized substrates. Here we disclose a metal-free, energy-transfer enabled highly regioselective intermolecular aminocarboxylation reaction for the single-step installation of both amine and ester functionalities into alkenes or (hetero)arenes. A bifunctional oxime oxalate ester was developed to simultaneously generate C-centred ester and N-centred iminyl radicals. This mild method features a remarkably broad substrate scope (up to 140 examples) and excellent tolerance of sensitive functional groups, and substrates that range from the simplest ethylene to complex (hetero)arenes can participate in the reaction, thus offering a general and practical access to β-amino acid derivatives.

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Fig. 1: Synthesis of β-amino acid derivatives.
Fig. 2: Synthetic applications.
Fig. 3: Mechanistic investigations.
Fig. 4: Proposed reaction mechanism and density functional theory calculations.

Data availability

Materials and methods, experimental procedures, mechanistic studies, computational studies, sensitivity assessment and NMR spectra are available in the Supplementary Information. CIF crystallographic data files and xyz coordinates of the optimized structures are available as Supplementary Files. Crystallographic data for the structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre, under deposition numbers CCDC 2113934 (1), 2113935 (S1), 2115949 (S3) and 2114975 (138). Copies of the data can be obtained free of charge via


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We thank J. Ma, X. Zhang, X. Yu, T. Hu (all WWU) and S. Chang (KAIST) for helpful assistance and discussion. Generous financial support from the Alexander von Humboldt Foundation and the Deutsche Forschungsgemeinschaft (SFB 858) is gratefully acknowledged. H.K. thanks the Institute for Basic Science (IBS-R010-D1) in the Republic of Korea for financial support.

Author information

Authors and Affiliations



F.G. and G.T. conceived the project. G.T., M.D. and P.B. performed the synthetic experiments. H.K. performed the density functional theory calculations. C.D. analysed the X-ray structures. G.T., M.D., H.K. and F.G. supervised the research and wrote the manuscript with contributions from all the authors.

Corresponding author

Correspondence to Frank Glorius.

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Peer review information

Nature Chemistry thanks Gabriela Oksdath-Mansilla and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Methods, Figs. 1–14 and Tables 1–4. Experimental data, synthesis and characterization data, supplementary discussion, computational and procedural details, x-ray crystallographic data, NMR spectra.

Supplementary Data 1

Crystallographic data for compound 1; CCDC reference 2113934.

Supplementary Data 2

Crystallographic data for compound 138; CCDC reference 2114975.

Supplementary Data 3

Crystallographic data for compound S1; CCDC reference 2113935.

Supplementary Data 4

Crystallographic data for compound S3; CCDC reference 2115949.

Supplementary Data 5

Cartesian coordinates for all calculated structures.

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Tan, G., Das, M., Keum, H. et al. Photochemical single-step synthesis of β-amino acid derivatives from alkenes and (hetero)arenes. Nat. Chem. 14, 1174–1184 (2022).

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