Conventional analytic techniques that measure ensemble averages and static disorder provide essential knowledge of the reaction mechanisms of organic and organometallic reactions. However, single-molecule junctions enable the in situ, label-free and non-destructive sensing of molecular reaction processes at the single-event level with an excellent temporal resolution. Here we deciphered the mechanism of Pd-catalysed Suzuki–Miyaura coupling by means of a high-resolution single-molecule platform. Through molecular engineering, we covalently integrated a single molecule Pd catalyst into nanogapped graphene point electrodes. We detected sequential electrical signals that originated from oxidative addition/ligand exchange, pretransmetallation, transmetallation and reductive elimination in a periodic pattern. Our analysis shows that the transmetallation is the rate-determining step of the catalytic cycle and clarifies the controversial transmetallation mechanism. Furthermore, we determined the kinetic and thermodynamic constants of each elementary step and the overall catalytic timescale of this Suzuki–Miyaura coupling. Our work establishes the single-molecule platform as a detection technology for catalytic organochemistry that can monitor transition-metal-catalysed reactions in real time.
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We acknowledge primary financial support from the National Key R&D Program of China (2017YFA0204901), the National Natural Science Foundation of China (21727806, 21933001 and 21772003) and the Tencent Foundation through the XPLORER PRIZE. The research at UCLA was supported by the US National Science Foundation (CHE 1764328). S.Z. and Z.L. appreciate the support from the High-Performance Computing Platform of the Center for Life Science at Peking University.
The authors declare no competing interests.
Peer review information Nature Nanotechnology thanks Nadim Darwish, Albert Poater and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Supplementary Sections 1–16, Figs. 1–39 and Tables 1–5.
Supplementary source data and original figures including compounds 1–3, Scheme 1, Figs. 1–39 and Tables 1–5.
Highly correlated fluorescent and current signals of the single-molecule catalyst site during the Suzuki–Miyaura cross-coupling.
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Yang, C., Zhang, L., Lu, C. et al. Unveiling the full reaction path of the Suzuki–Miyaura cross-coupling in a single-molecule junction. Nat. Nanotechnol. 16, 1214–1223 (2021). https://doi.org/10.1038/s41565-021-00959-4
Nature Nanotechnology (2021)