Pd-Catalyzed C-N Coupling Reactions Facilitated by Organic Bases: Mechanistic Investigation Leads to Enhanced Reactivity in the Arylation of Weakly Binding Amines
Pd-Catalyzed C-N Coupling Reactions Facilitated by Organic Bases: Mechanistic Investigation Leads to Enhanced Reactivity in the Arylation of Weakly Binding Amines
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DOI：
10.1021/acscatal.9b00981
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发表时间：
2019-05-01
期刊：
影响因子：
12.9
通讯作者：
Buchwald, Stephen L.
中科院分区：
文献类型：
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作者：
Dennis, Joseph M.;White, Nicholas A.;Buchwald, Stephen L.
在Pd催化的C-N交叉偶联反应中使用可溶性有机胺碱的能力为与采用传统的非均相反应条件相关的许多问题提供了期待已久的解决方案。然而，很少有人知道这些碱在催化循环中的精确功能，或关于碱结构的变化对催化剂反应性的影响。利用F-19 NMR分析了不同有机碱促进的C-N偶联反应的动力学行为。在使用DBU的苯胺偶联反应的情况下，静止状态是DBU结合的氧化加成络合物，LPd（DBU）（Ar）X，并且发现该反应被碱抑制。然而，通常，取决于所选有机碱的结合性质，增加碱的浓度可对反应速率具有正面或负面影响。此外，反应中使用的芳基三氟甲磺酸酯的电子性质直接影响反应速率。最快的反应速率与电子中性的芳基三氟甲磺酸酯，而最慢的观察高度富电子和缺电子基板。我们提出了一个模型，其中的周转限制步骤的催化循环是依赖于相对亲核性的碱，相比，胺。这一假设指导发现了新的反应条件，用于偶联弱结合胺，包括仲芳基胺，其在我们的原始方案中是不反应的亲核试剂。
The ability to use soluble organic amine bases in Pd-catalyzed C-N cross-coupling reactions has provided a long-awaited solution to the many issues associated with employing traditional, heterogeneous reaction conditions. However, little is known about the precise function of these bases in the catalytic cycle or about the effect of variations in base structure on catalyst reactivity. We used F-19 NMR to analyze the kinetic behavior of C-N coupling reactions facilitated by different organic bases. In the case of aniline coupling reactions employing DBU, the resting state was a DBU-bound oxidative addition complex, LPd(DBU)(Ar)X, and the reaction was found to be inhibited by base. Generally, however, depending on the binding properties of the chosen organic base, increasing the concentration of the base can have a positive or negative influence on the reaction rate. Furthermore, the electronic nature of the aryl triflate employed in the reaction directly affects the reaction rate. The fastest reaction rates were observed with electronically neutral aryl triflates, while the slowest were observed with highly electron-rich and electron-deficient substrates. We propose a model in which the turnover-limiting step of the catalytic cycle is dependent on the relative nucleophilicity of the base, compared to that of the amine. This hypothesis guided the discovery of new reaction conditions for the coupling of weakly binding amines, including secondary aryl amines, which were unreactive nucleophiles in our original protocol.