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Enantioselective dearomative prenylation of indole derivatives

Nature Catalysisvolume 1pages601608 (2018) | Download Citation

Abstract

Prenylation is a ubiquitous process common to almost all living organisms, and a key transformation in organic synthesis. Dearomative prenylation reactions of tryptophan derivatives lead to various prenylated indoline alkaloids with diverse biological activities. However, enantioselective dearomative prenylations without a pre-installed stereogenic centre in the substrate have not been reported. Here, we show that a small molecule-based catalytic system derived from a commercially available palladium precursor and a chiral phosphoramidite ligand (allylphos) can catalyse the enantioselective dearomative prenylation of indole derivatives, which tolerates a much broader substrate scope than those of known enzymatic dearomative prenylation processes. Enantioselective dearomative geranylation and farnesylation reactions also proceed smoothly under the standard conditions. The concise total or formal syntheses of a series of natural products can be realized using this catalytic system. The mechanistic investigations provide deep insights for the further design of chiral ligands and catalysts for asymmetric reactions.

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Acknowledgements

We thank the National Key Research and Development Program of China (2016YFA0202900), National Basic Research Program of China (973 Program 2015CB856600), National Natural Science Foundation of China (21332009 and 21572252), Strategic Priority Research Program (XDB20000000) and Key Research Program of Frontier Sciences (QYZDYSSWSLH012) of the Chinese Academy of Sciences, and the Science and Technology Commission of Shanghai Municipality (16XD1404300) for generous financial support, and X. Leng and J. Sun (SIOC) for X-ray crystallographic analysis.

Author information

Author notes

  1. These authors contributed equally: Hang-Fei Tu, Xiao Zhang.

Affiliations

  1. State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China

    • Hang-Fei Tu
    • , Xiao Zhang
    • , Chao Zheng
    • , Min Zhu
    •  & Shu-Li You
  2. Collaborative Innovation Center of Chemical Science and Engineering, Tianjin, China

    • Shu-Li You

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Contributions

H.-F.T. and X.Z. were involved in the discovery, design and development of the enantioselective dearomative prenylation of indole derivatives. X.Z. synthesized allylphos. H.-F.T. performed the total syntheses of the natural products. H.-F.T. and C.Z. performed the mechanistic studies. M.Z. was involved in the synthesis of substrates. S.-L.Y. conceived and supervised the project. H.-F.T., C.Z. and S.-L.Y. wrote the manuscript with revisions suggested by all authors.

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Shu-Li You.

Supplementary information

  1. Supplementary Information

    Supplementary Methods, Supplementary Figures 1–3, Supplementary Tables 1–17, Supplementary References

  2. Crystallographic data

    CIF for compound C1; CCDC reference: 1822391

  3. Crystallographic data

    CIF for compound C2; CCDC reference: 1822392

  4. Crystallographic data

    CIF for compound 22; CCDC reference: 1822393

  5. Crystallographic data

    CIF for compound (R)-L1; CCDC reference: 1822394

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DOI

https://doi.org/10.1038/s41929-018-0111-8