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Electrochemical chemo- and regioselective arylalkylation, dialkylation and hydro(deutero)alkylation of 1,3-enynes

Nature Synthesis volume 2, pages 1068–1081 (2023)Cite this article

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Abstract

The development of general and efficient strategies for the construction of allenes is important due to their wide applications. Although few protocols have been developed via the 1,4-difunctionalization of 1,3-enynes under thermal or photoredox conditions, the mild and robust methodology for dicarbofunctionalization and hydroalkylation remains unexplored. In the present study, we report an electrochemical multicomponent protocol for the chemo- and regioselective difunctionalization of 1,3-enynes. In particular, 1,4-arylalkylation and unsymmetrical dialkylation have been realized via electro- and nickel dual catalysis using graphite/nickel foam and zinc/nickel foam as electrodes, respectively. The use of a Zn/reticulated vitreous carbon electrode led to efficient 1,4-hydro(deutero)alkylation in the absence of a metal catalyst. A wide range of structurally diverse tri- and tetra-substituted allenes were easily prepared with good efficiency and excellent regioselectivity under mild reaction conditions. Notably, a series of natural product- and drug-derived substrates could undergo late-stage functionalization to generate the corresponding complex allenes.

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Fig. 1: The development of electrochemical difunctionalization of 1,3-enynes.
Fig. 2: Synthetic applications and mechanism studies.
Fig. 3: DFT calculation and proposed mechanisms.

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Data availability

The authors declare that the data generated in the present study are available within the article and the Supplementary Information. The cartesian coordinates of DFT calculations are available in Supplementary Data 1.

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Acknowledgements

This work was financially supported by the King Abdullah University of Science and Technology (KAUST) and the Saudi Arabia, Office of Sponsored Research (URF/1/4025). C.Z. acknowledges the KAUST Supercomputing Laboratory for providing computational resources from the supercomputer Shaheen II (k1284).

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Author notes

  1. These authors contributed equally: Chen Zhu, Haifeng Chen.

Authors and Affiliations

  1. KAUST Catalysis Center, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia

    Chen Zhu, Haifeng Chen, Huifeng Yue & Magnus Rueping

  2. Eastern Institute for Advanced Study, Eastern Institute of Technology, Ningbo, China

    Chen Zhu

  3. Key Laboratory of Molecule Synthesis and Function Discovery (Fujian Province University), College of Chemistry, Fuzhou University, Fuzhou, China

    Huifeng Yue

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Contributions

C.Z., H.Y. and M.R. conceived and designed the project. C.Z., H.C. and H.Y. optimized the reaction conditions. H.C. performed and analysed the experiments. C.Z. and H.C. performed the experimental mechanistic studies. C.Z. performed the theoretical calculations. C.Z., H.Y. and M.R. co-wrote the manuscript. M.R. directed the whole research.

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Correspondence to Huifeng Yue or Magnus Rueping.

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Supplementary information

Supplementary sections 1–10, including experimental details, Figs. 1–6 and Tables 1 and 2.

Supplementary Data 1

The cartesian coordinates of DFT calculations.

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Zhu, C., Chen, H., Yue, H. et al. Electrochemical chemo- and regioselective arylalkylation, dialkylation and hydro(deutero)alkylation of 1,3-enynes. Nat. Synth 2, 1068–1081 (2023). https://doi.org/10.1038/s44160-023-00349-9

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