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Electrochemical gold-catalysed biocompatible C(sp2)–C(sp) coupling

Nature Synthesis volume 2, pages 338–347 (2023)Cite this article

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Abstract

Gold-catalysed oxidative coupling reactions often require strong oxidants because of the high redox potential of Au(i)/Au(iii) (1.41 V versus the saturated calomel electrode), resulting in poor reaction economy and functional group compatibility. Here we report a dinuclear gold-catalysed C(sp2)–C(sp) coupling reaction between structurally diverse alkynes and arylhydrazines under electrochemical conditions. This approach provides a practical oxidative C–C coupling reaction that avoids the use of synthetic oxidants and instead produces H2. This method exhibits excellent functional group compatibility towards compounds such as alcohols, amines, sulfides and electron-rich arenes, which possess functional groups sensitive to oxidizing agents. This synthetic robustness is further shown by the successful late-stage modification of different kinds of alkynes tethered to biomolecules such as amino acids, peptides, nucleotides and saccharides. Mechanistic studies suggest a first aryl radical oxidative addition step with Au(i), followed by anodic oxidation to generate the highly electrophilic Ar–Au(iii) species for subsequent σ-activation of alkynes.

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Fig. 1: The importance of alkynes in organic synthesis (appealing for gold-catalysed C(sp)–C(sp2) coupling reactions and biocompatibility).
Fig. 2: Different ligands for the gold catalysts.
Fig. 3: Mechanistic studies.
Fig. 4: Proposed reaction mechanism.

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All of the data supporting the findings of this study are available within the article and its Supplementary Information files. Source data are provided with this paper.

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Acknowledgements

We thank the National Natural Science Foundation of China (22122103 and 21971108 to J.X.), National Key Research and Development Program of China (2021YFC2101901 and 2022YFA15032 to J.X.), Fundamental Research Funds for the Central Universities (020514380252, 020514380272 to J.X.) and China Postdoctoral Science Foundation (2020TQ0139 and 2021M701661 to C.-G.Z.) for financial support. We acknowledge Xu Cheng at Nanjing University for insightful discussion and assistance. All theoretical calculations were performed at the High-Performance Computing Center of Nanjing University. We also acknowledge Yaohang Cheng, Yantao Li and Nian Li at Nanjing University for reproduction of the experimental procedures for products 4, 33 and 39.

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  1. State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China

    Hao Liang, Yilitabaier Julaiti, Chuan-Gang Zhao & Jin Xie

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  1. Hao Liang
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J.X. and H.L. conceived of and designed the project. H.L., Y.J. and C.-G.Z. performed and analysed the experimental data. J.X. wrote the manuscript with input from all authors.

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Correspondence to Jin Xie.

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Nature Synthesis thanks Huan-Ming Huang, Xiaodong Shi and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Peter Seavill, in collaboration with the Nature Synthesis team.

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Liang, H., Julaiti, Y., Zhao, CG. et al. Electrochemical gold-catalysed biocompatible C(sp2)–C(sp) coupling. Nat. Synth 2, 338–347 (2023). https://doi.org/10.1038/s44160-022-00219-w

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