Elusive transmetalation intermediate in copper-catalyzed conjugate additions: direct NMR detection of an ethyl group attached to a binuclear phosphoramidite copper complex.
Elusive transmetalation intermediate in copper-catalyzed conjugate additions: direct NMR detection of an ethyl group attached to a binuclear phosphoramidite copper complex.
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DOI：
10.1021/ja504577t
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发表时间：
2014-08
影响因子：
15
通讯作者：
Felicitas von Rekowski;C. Koch;R. Gschwind
中科院分区：
文献类型：
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作者：
Felicitas von Rekowski;C. Koch;R. Gschwind
铜催化的不对称共轭加成反应是一种非常有效且应用广泛的对映选择性碳-碳键生成方法。然而，到目前为止，对这些著名反应的结构和机理的了解非常有限。本文介绍了铜催化反应中金属转化中间体的首次直接实验检测。(1)H,(31)P HMBC光谱的特殊组合允许识别具有烷基和铜配合物之间化学键的配合物。对于这些过渡金属中间体的结构表征，采用了一种特殊的方法，其中使用对映纯配体的样品与使用对映体配体混合物的样品进行比较。实验首次证明，在金属转化过程中，二聚体铜的配合物结构被保留，在铜原子上提供了一个混合的三角形/四面体配位中间体。此外，检测到具有一个配体的单体中间体，但没有检测到具有两个配体的中间体。这些实验结果，结合众所周知的合成应用中配体与铜的最佳比例为2:1，使我们能够提出双核金属转化中间体是铜催化的不对称共轭加成反应的活性物质。这是对金属转化中间体结构的第一次直接实验洞察，有望支持对这类重要反应的机理和理论理解，并使其进一步的合成发展成为可能。此外，本文提出的用于鉴定和表征低于(1)H NMR光谱检测限的中间体的特殊NMR方法也可应用于其他类型的催化剂。
Copper-catalyzed asymmetric conjugate addition reactions are a very powerful and widely applied method for enantioselective carbon-carbon bond formation. However, structural and mechanistic insight into these famous reactions has been very limited so far. In this article, the first direct experimental detection of transmetalation intermediates in copper-catalyzed reactions is presented. Special combinations of (1)H,(31)P HMBC spectra allow for the identification of complexes with chemical bonds between the alkyl groups and the copper complexes. For the structural characterization of these transmetalation intermediates, a special approach is applied, in which samples using enantiopure ligands are compared with samples using enantiomeric mixtures of ligands. It is experimentally proven, for the first time, that the dimeric copper complex structure is retained upon transmetalation, providing an intermediate with mixed trigonal/tetrahedral coordination on the copper atoms. In addition, monomeric intermediates with one ligand, but no intermediates with two ligands, are detected. These experimental results, in combination with the well-known optimal ligand-to-copper ratio of 2:1 in synthetic applications, allow us to propose that a binuclear transmetalation intermediate is the reactive species in copper-catalyzed asymmetric conjugate addition reactions. This first direct experimental insight into the structure of the transmetalation intermediate is expected to support the mechanistic and theoretical understanding of this important class of reactions and to enable their further synthetic development. In addition, the special NMR approach presented here for the identification and characterization of intermediates below the detection limit of (1)H NMR spectra can be applied also to other classes of catalyses.