Department of Chemistry & Biochemistry, University of California, Los Angeles, California 90095, USA.
Acc Chem Res. 2010 Oct 19;43(10):1352-63. doi: 10.1021/ar1000605.
Aromatic heterocycles are a prominent feature within natural products and pharmaceuticals and considerable efforts are directed toward their synthesis and functionalization. These molecules also appear as unwanted impurities in carbon-based fuels, and processes that fragment them are of increasing interest. Early transition metal-carbon bonds show diverse reactivity toward aromatic heterocycles: researchers have reported both functionalization, relevant to synthetic efforts, and ring opening, relevant to their removal from fuels. In particular, chelating ferrocene-diamides possess unique electronic characteristics as ancillary ligands that enable a wide range of reactivity behaviors for the resulting metal complexes. In this Account, we describe our efforts to understand the reactivity of group 3 metal and uranium alkyl complexes supported by these organometallic ligands toward aromatic N-heterocycles. Two geometrically related ancillary ligands were investigated: 1,1'-ferrocenylene-diamides and pincer-type pyridine-diamides. A substrate-dependent behavior was observed. For example, all the benzyl metal complexes cleaved 1-methylimidazole. In the case of pyridines, differences in reactivity were identified: C-H activation and C-C coupling occurred with substituted pyridines, while alkyl transfer predominated with isoquinoline and chelating pyridines. The products of the C-C coupling or the alkyl-transfer reactions underwent subsequent hydrogen transfer: within the same ring for the substituted pyridines and between two different heterocycles for isoquinoline and chelating pyridines. The comparison between yttrium and lutetium benzyl complexes supported by ferrocene- or pyridine-diamide ligands indicated that similar reactions occurred for specific substrates (1-methylimidazole, 2-picoline, and isoquinoline). A broader range of reaction types and a larger substrate scope were identified, however, for the ferrocene than for the pyridine-type complexes. Based on the reactions discussed in this Account and on isolated examples drawn from the literature, we conclude that the ferrocene-diamides represent a versatile ligand framework. We propose that iron's ability to accommodate changes in the electronic density at the metal center more readily than classical supporting ligands leads to the privileged status of these organometallic ancillary ligands.
芳杂环是天然产物和药物中的一个重要特征，人们投入了大量的精力来合成和功能化这些化合物。这些分子也作为杂质出现在碳基燃料中，因此能够使它们断裂的反应过程引起了人们越来越多的关注。早期的过渡金属-碳键对芳杂环表现出不同的反应活性：研究人员已经报道了功能化（与合成努力相关）和开环（与从燃料中去除相关）。特别是，螯合二茂铁二酰胺作为辅助配体具有独特的电子特性，使所得金属配合物具有广泛的反应活性。在本报告中，我们描述了我们努力理解这些有机金属配体支持的第三族金属和铀烷基配合物对芳族 N-杂环的反应性。我们研究了两种几何相关的辅助配体：1,1'-二茂铁二酰胺和钳式吡啶二酰胺。观察到了底物依赖性行为。例如，所有苄基金属配合物都能断裂 1-甲基咪唑。对于吡啶，反应活性存在差异：取代吡啶发生 C-H 活化和 C-C 偶联，而异喹啉和螯合吡啶则主要发生烷基转移。C-C 偶联或烷基转移反应的产物经历了随后的氢转移：取代吡啶在同一环中，而异喹啉和螯合吡啶在两个不同的杂环之间。钇和镥的苄基配合物与二茂铁或吡啶二酰胺配体的比较表明，对于特定的底物（1-甲基咪唑、2-吡啶和异喹啉），会发生类似的反应。然而，与吡啶型配合物相比，二茂铁型配合物具有更广泛的反应类型和更大的底物范围。基于本报告中讨论的反应以及从文献中提取的孤立实例，我们得出结论，二茂铁二酰胺代表了一种多功能的配体框架。我们提出，铁在金属中心容纳电子密度变化的能力比经典的支撑配体更容易，这导致了这些有机金属辅助配体的特殊地位。
