该报告描述了Ni膦催化剂的详细研究,该催化剂用于二氯吡啶与含卤素的(杂)芳基硼酸的Suzuki-Miyaura偶联。对于大多数膦配体,这些转化提供单-和二芳基化交叉偶联产物的混合物以及硼酸的竞争性低聚。然而,配体筛选显示PPh2Me和PPh3提供了相对于二芳基化的高收率和单芳基化的选择性以及硼酸的最小竞争性低聚。对这些反应的选择性进行了一些关键观察,包括:(1)膦配体提供高选择性的单芳基化落在狭窄的托尔曼锥角范围内(136°至157°);(2)更多的富电子三烷基膦主要提供二芳基化产物,而富含电子的二-和三芳基膦有利于单芳基化;(3)通过分子内氧化加成进行二芳基化;和(4)溶剂(MeCN)在实现高单芳基化选择性中起关键作用。实验和DFT研究表明,所有这些数据都可以根据关键中间体的反应性来解释:单芳基化产物的NiO-π复合物。随着更大的,更多富含电子的三烷基膦配体,该π配合物经历分子内氧化加成比MeCN溶剂的配体取代更快,导致选择性二芳基化。相比之下,具有相对较小的二-和三芳基膦配体,MeCN的缔合配体取代与氧化加成竞争,导致选择性形成单芳基化产物。用各种二氯吡啶和氯取代的芳基硼酸证明了该方法的普遍性。此外,利用最佳配体(PPh2Me)和溶剂(MeCN)来实现更广泛的二氯芳烃底物的Ni催化的单芳基化。
This report describes a detailed study of Ni phosphine catalysts for the Suzuki-Miyaura coupling of dichloropyridines with halogen-containing (hetero)aryl boronic acids. With most phosphine ligands these transformations afford mixtures of mono- and diarylated cross-coupling products as well as competing oligomerization of the boronic acid. However, a ligand screen revealed that PPh2Me and PPh3 afford high yield and selectivity for monoarylation over diarylation as well as minimal competing oligomerization of the boronic acid. Several key observations were made regarding the selectivity of these reactions, including: (1) phosphine ligands that afford high selectivity for monoarylation fall within a narrow range of Tolman cone angles (between 136° and 157°); (2) more electron-rich trialkylphosphines afford predominantly diarylated products, while less-electron rich di- and triarylphosphines favor monoarylation; (3) diarylation proceeds via intramolecular oxidative addition; and (4) the solvent (MeCN) plays a crucial role in achieving high monoarylation selectivity. Experimental and DFT studies suggest that all these data can be explained based on the reactivity of a key intermediate: a Ni0-π complex of the monoarylated product. With larger, more electron-rich trialkylphosphine ligands, this π complex undergoes intramolecular oxidative addition faster than ligand substitution by the MeCN solvent, leading to selective diarylation. In contrast, with relatively small di- and triarylphosphine ligands, associative ligand substitution by MeCN is competitive with oxidative addition, resulting in selective formation of monoarylated products. The generality of this method is demonstrated with a variety of dichloropyridines and chloro-substituted aryl boronic acids. Furthermore, the optimal ligand (PPh2Me) and solvent (MeCN) are leveraged to achieve the Ni-catalyzed monoarylation of a broader set of dichloroarene substrates.