Department of Chemistry, Chemistry Research Laboratories , University of Oxford , Mansfield Road , Oxford OX1 4TA , United Kingdom.
School of Chemistry , University of Melbourne , Parkville , VIC 3010 , Australia.
J Am Chem Soc. 2020 Feb 19;142(7):3564-3576. doi: 10.1021/jacs.9b13260. Epub 2020 Feb 7.
Pyridine and related heterocyclic sulfinates have recently emerged as effective nucleophilic coupling partners in palladium-catalyzed cross-coupling reactions with (hetero)aryl halides. These sulfinate reagents are straightforward to prepare, stable to storage and coupling reaction conditions, and deliver efficient reactions, thus offering many advantages, compared to the corresponding boron-derived reagents. Despite the success of these reactions, there are only scant details of the reaction mechanism. In this study, we use structural and kinetic analysis to investigate the mechanism of these important coupling reactions in detail. We compare a pyridine-2-sulfinate with a carbocyclic sulfinate and establish different catalyst resting states, and turnover limiting steps, for the two classes of reagent. For the carbocyclic sulfinate, the aryl bromide oxidative addition complex is the resting state intermediate, and transmetalation is turnover-limiting. In contrast, for the pyridine sulfinate, a chelated Pd(II) sulfinate complex formed post-transmetalation is the resting-state intermediate, and loss of SO from this complex is turnover-limiting. We also investigated the role of the basic additive potassium carbonate, the use of which is crucial for efficient reactions, and deduced a dual function in which carbonate is responsible for the removal of free sulfur dioxide from the reaction medium, and the potassium cation plays a role in accelerating transmetalation. In addition, we show that sulfinate homocoupling is responsible for converting Pd(OAc) to a catalytically active Pd(0) complex. Together, these studies shed light on the challenges that must be overcome to deliver improved, lower temperature versions of these synthetically important processes.
吡啶和相关杂环亚磺酸盐最近已成为钯催化交叉偶联反应中与（杂）芳基卤化物有效亲核偶联伙伴。这些亚磺酸盐试剂易于制备，在储存和偶联反应条件下稳定，并且提供有效的反应，因此与相应的硼衍生试剂相比具有许多优势。尽管这些反应取得了成功，但有关反应机制的细节却很少。在这项研究中，我们使用结构和动力学分析详细研究了这些重要偶联反应的机制。我们比较了吡啶-2-亚磺酸盐和碳环亚磺酸盐，并为这两类试剂建立了不同的催化剂休眠状态和周转限制步骤。对于碳环亚磺酸盐，芳基溴化物的氧化加成络合物是休眠状态中间体，而转金属化是周转限制步骤。相比之下，对于吡啶亚磺酸盐，形成于转金属化之后的螯合 Pd(II)亚磺酸盐络合物是休眠状态中间体，并且该络合物中 SO 的损失是周转限制步骤。我们还研究了碱性添加剂碳酸钾的作用，其使用对于高效反应至关重要，并且推断出碳酸钾具有双重功能，即负责从反应介质中除去游离的二氧化硫，以及钾阳离子在加速转金属化方面发挥作用。此外，我们表明亚磺酸盐的同偶联反应负责将 Pd(OAc)转化为催化活性的 Pd(0)配合物。总之，这些研究阐明了在开发这些具有重要合成意义的过程的改进型、低温版本时必须克服的挑战。
