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Metal-free photosensitized oxyimination of unactivated alkenes with bifunctional oxime carbonates

Abstract

The 1,2-aminoalcohol motif is one of the most prevalent structural components found in high-value organic molecules, including pharmaceuticals and natural products. Generally, its preparation requires pre-functionalized substrates and manipulations of one functional group at a time to achieve the desired regioisomer. Herein, we describe a metal-free photosensitization protocol for the installation of both amine and alcohol functionalities into alkene feedstocks in a single step. This approach is enabled by the identification of oxime carbonate as a suitable bifunctional source of both oxygen- and nitrogen-centred radicals for addition across alkenes with complementary regioselectivity compared to Sharpless aminohydroxylation. Use of orthogonal protection for amine and alcohol functionalities enables the direct synthetic diversification of one functional handle without influencing the other. With the use of readily available starting materials, convergent synthesis and mild reaction conditions, this process is well suited for use in various synthetic endeavours.

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Fig. 1: Strategies for vicinal aminoalcohol synthesis.
Fig. 2: Development of an intermolecular radical oxyimination of alkenes.
Fig. 3: Substrate scope of the intermolecular oxyimination of alkenes.
Fig. 4: Application of the metal-free oxyimination of alkenes.
Fig. 5: Mechanistic investigations and proposed reaction mechanism.

Data availability

Details about materials and methods, experimental procedures, mechanistic studies, characterization data and NMR spectra are available in the Supplementary Information. Additional data are available from the corresponding author upon reasonable request. The atomic coordinates of the optimized models for triplet energy calculation are provided in Supplementary Data 1. Crystallographic data are available from the Cambridge Crystallographic Data Centre with the following codes: 24 (CCDC 2004569), 26 (CCDC 2027139), 27 (CCDC 2004570) and 36 (CCDC 2027138).

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Acknowledgements

This work was generously supported by the Alexander von Humboldt Foundation (T.P.) and the Deutsche Forschungsgemeinschaft (Leibniz Award and SFB 858). We thank F. Strieth-Kalthoff, A. Köhrer, X. Zhang and A. Das for experimental and technical assistance, and F. Sandfort, J. L. Schwarz, P. Bellotti, T. Dalton and S. Singha for helpful discussions.

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Authors and Affiliations

Authors

Contributions

T.P. and F.G. conceived this work. T.P. and M.D. performed all the experiments and analysed the data. C.G.D. collected and analysed the X-ray crystallographic data. T.P. and F.G. prepared the manuscript with contributions from all authors.

Corresponding author

Correspondence to Frank Glorius.

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The authors declare no competing interests.

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Peer review information Nature Catalysis thanks the anonymous reviewers for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Methods, Tables 1–3, Figs. 1–14 and Refs. 1–32.

Supplementary Data 1

Computed atomic coordinates.

Supplementary Data 2

Crystallographic data of compound 24.

Supplementary Data 3

Crystallographic data of compound 26.

Supplementary Data 4

Crystallographic data of compound 27.

Supplementary Data 5

Crystallographic data of compound 36.

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Patra, T., Das, M., Daniliuc, C.G. et al. Metal-free photosensitized oxyimination of unactivated alkenes with bifunctional oxime carbonates. Nat Catal 4, 54–61 (2021). https://doi.org/10.1038/s41929-020-00553-2

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