西湖大学石航团队报道了钌/η - 5-苯氧催化苯酚与胺的胺化反应。相关研究成果发表在2024年5月31日出版的《美国化学会杂志》。

已知钌（II）配合物通过π-配位与含苯化合物形成η6-芳烃配合物，这一性质被广泛用于引发游离芳烃不常见的反应。一个主要的例子是亲核芳香取代，其中钌络合的芳基卤化物经历亲核攻击，能够通过用亲核试剂取代卤化物直接合成各种芳香化合物。然而，这种活化依赖于Ru（II）物种的吸电子效应，并且受到η6-芳烃对芳烃交换的阻力的阻碍。在之前的催化研究中，配体设计的重点一直集中在促进芳烃交换上。

该文中，研究人员将钌的活化策略扩展到苯酚的umpolung取代反应中。胺化通过苯酚和胺之间的直接缩合进行，关键中间体被鉴定为由市售钌催化剂原位生成的[双（η5-苯氧基）Ru]。与研究充分的环戊二烯基（Cp）型配体相比，研究证明了η5-苯氧基序作为Cp的优越替代物，在两个关键方面有助于苯酚的胺化：其给电子较少的性质增强了钌单元的撤回效应，促进了苯酚络合物上的取代；其在芳烃交换中的独特行为用催化量的金属进行胺化。

此外，发现其中苯氧基作为受体的氢键对于取代是重要的。这种钌催化的胺化的多功能性通过与表现出各种电子性质的，各种酚类以及广泛的伯胺进行反应来验证。

该项工作体现了通过创新的配体开发扩大催化中π-配位活化的范围。

附：英文原文

Title: Ruthenium/η5-Phenoxo-Catalyzed Amination of Phenols with Amines

Author: Kai Chen, Yixuan Ma, Yunzhi Lin, Jia-Yue Li, Hang Shi

Issue&Volume: May 31, 2024

Abstract: Ruthenium(II) complexes are known to form η6-arene complexes with benzene-containing compounds through π-coordination, a property extensively utilized to initiate reactions not typically observed with free arenes. A prime example is nucleophilic aromatic substitution, where ruthenium-complexed aryl halides undergo nucleophilic attack, allowing the direct synthesis of diverse aromatic compounds by displacing halides with nucleophiles. However, this activation relies on the electron-withdrawing effect of the Ru(II) species, as well as is hindered by the resistance of η6-arenes to arene exchange. In the previous pursuit of catalysis, the emphasis of ligand design has centered on promoting arene exchange. In this study, we extended the ruthenium activation strategy to umpolung substitution reactions of phenols. The amination proceeds through a direct condensation between phenols and amines, with a key intermediate identified as [bis(η5-phenoxo)Ru], which is in situ generated from a commercially available ruthenium catalyst. In comparison with the well-studied cyclopentadienyl (Cp) type ligands, we demonstrated that an η5-phenoxo motif, as a superior alternative to Cp, contributes to the amination of phenols in two crucial ways: its less electron-donating nature enhances the withdrawing effect of the ruthenium unit, facilitating substitution on the phenol complex; its distinctive behavior in arene exchange allows for conducting the amination with a catalytic amount of metal. Additionally, hydrogen bonding, wherein the phenoxo serves as the acceptor, was found to be important for the substitution. The versatility of this ruthenium-catalyzed amination was validated by performing reactions with a diverse array of phenols exhibiting various electronic properties, in combination with a wide range of primary amines. This work exemplifies the expansion of the scope of π-coordination activation in catalysis through innovative ligand development.

DOI: 10.1021/jacs.4c02089

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c02089