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.

测量整体平均值和静态无序的常规分析技术提供了有机和有机金属反应的反应机制的基本知识。然而，单分子结能够以出色的时间分辨率在单事件水平上实现分子反应过程的原位、无标记和无损传感。在这里，我们通过高分辨率单分子平台破译了 Pd 催化的 Suzuki-Miyaura 耦合机制。通过分子工程，我们将单分子 Pd 催化剂共价集成到纳米间隙石墨烯点电极中。我们检测到源自周期性模式的氧化添加/配体交换、预转金属化、转金属化和还原消除的顺序电信号。我们的分析表明，金属转移是催化循环的速率决定步骤，并阐明了有争议的金属转移机制。此外，我们确定了每个基本步骤的动力学和热力学常数以及这种 Suzuki-Miyaura 耦合的整体催化时间尺度。我们的工作建立了单分子平台作为催化有机化学的检测技术，可以实时监测过渡金属催化的反应。