Direct one-pot reductive N-alkylation of nitroarenes by using alcohols with supported gold catalysts.
Direct one-pot reductive N-alkylation of nitroarenes by using alcohols with supported gold catalysts.
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DOI：
10.1002/chem.201100393
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发表时间：
2011-06
期刊：
影响因子：
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通讯作者：
Chunlin Tang;Lin He;Yongmei Liu;Yong Cao;Heyong He;Kangnian Fan
中科院分区：
文献类型：
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作者：
Chunlin Tang;Lin He;Yongmei Liu;Yong Cao;Heyong He;Kangnian Fan
C-N键的形成是化学中最重要的转变之一，因为含氮化合物，特别是胺及其衍生物，是各种有机分子的通用构建单元和各种生物活性化合物的重要前体。虽然有几种方法是已知的C-N键的合成，在温和和无废物的条件下使用简单，廉价，易得的原料制备仍然是一个具有挑战性的目标。过渡金属催化的胺与醇的偶联反应（也称为氢自转移过程）是一种原子经济的、环境友好的碳氮键构建方法，特别是仲胺的制备。虽然已经报道了许多用于这种转化的有效催化剂，但是可以解决均相体系的问题的易于回收和可再循环的多相催化剂的开发引起了特别的关注。据我们所知，很少有非均相催化剂体系的报道，使有效的和选择性的N-烷基化胺与醇在简单，温和，和环境友好的条件下。硝基芳烃是一种廉价易得的有机化合物，硝基化合物的还原是制备许多医药和精细化学品的关键步骤。尽管硝基化合物的还原已经有了许多成熟的方法，但在温和的反应条件下提供高化学选择性和区域选择性的催化方法的发展仍然是一个具有挑战性的问题。至于仲胺的合成，直接使用市售的和廉价的硝基芳烃和醇作为起始原料是非常有吸引力的，特别是当可以使用单一催化剂体系时。在这种有价值的一锅多步转化中，醇可以想象地提供两种可能的功能：作为硝基还原的氢源和作为基于催化氢转移的烷基化试剂。虽然需要过量的醇来确保反应的完成（参见可能的反应化学计量的支持信息），但这种转化的操作简单性对于以更直接的方式简洁地合成N-取代胺可能具有实际优势。与胺与醇的胺化反应取得的巨大进展相比，硝基芳烃与醇的直接胺化反应的报道还很少。迄今为止，只有三个Ru基均相系统已被报道。然而，这些均相催化剂在催化剂的回收/再循环和金属络合物的特殊处理的必要性方面存在问题。从可持续的观点来看，高度期望使用无配体的非均相催化剂的更有效的反应。在过去的五年里，我们一直对负载型金纳米颗粒（NPs）的独特催化性能感兴趣，并参与其在可持续有机合成中的应用。最近，我们已经表明，非常小的Au纳米粒子（约。1.8 nm）沉积在TiO 2（Au/TiO 2-VS; VS=非常小）上作为一种有效的多相催化剂，用于在借氢条件下以优异的产率清洁和原子效率的一系列胺与醇的单-N-烷基化。鉴于金体系在胺与醇的胺化反应中的突出效率，我们设想金介导的借氢策略可以为硝基芳烃与醇在温和条件下的直接胺化提供一种绿色和有效的方案。本文首次报道了简单的Au/TiO 2-VS体系催化硝基芳烃与醇直接缩合生成仲胺或叔胺的反应。值得注意的是，该反应可以在无配体和无碱的条件下有效地进行，而无需任何外部氢源。据我们所知，这项研究也形成了第一个报告的一锅选择性制备亚胺从硝基芳烃和醇通过使用非均相金介导的“催化氢转移”程序。基于我们先前在非均相Au催化的胺/醇偶联化学中的结果，优化研究以在Au/TiO 2-VS（0.5摩尔%的Au，参见Sup[a] C.-2010）存在下硝基苯（1a）与8当量苯甲醇（2a）的直接胺化开始。H.唐湖，澳-地他，Y博士。- M. Liu教授Y博士Cao，Prof. Dr. H. Y.他，K教授- N.复旦大学化学系上海市分子催化与创新材料重点实验室，上海200433（P.R.中国）传真：（+86 021 -65643774电子邮件：yongcao@fudan.edu.cn本文的支持信息可在http://dx.doi.org/10.1002/chem.201100393下获得。
The formation of C N bonds is one of the most important transformations in chemistry because nitrogen-containing compounds, particularly amines and their derivatives, are versatile building blocks for various organic molecules and essential precursors to a variety of biologically active compounds. Although several methods are known for the synthesis of C N bonds, preparation under mild and wastefree conditions using simple, inexpensive, and readily available feedstock is still a challenging goal. The transitionmetal-catalyzed coupling of amines with alcohols by using a hydrogen-borrowing strategy (also known as a hydrogenautotransfer process) has proven to be an atom-economical and environmentally attractive method for the construction of C N bonds, especially for secondary amine preparation. Although many efficient catalysts for such transformations have been reported, 4] the development of easily recoverable and recyclable heterogeneous catalysts that can solve the problem of the homogeneous systems has attracted special attention. To the best of our knowledge, few heterogeneous catalyst systems have been reported that enable efficient and selective N-alkylation of amines with alcohols under simple, mild, and environmentally benign conditions. Nitroarenes are cheap and readily available organic compounds and the reduction of nitro compounds is a key step in the preparation of many pharmaceutical agents and fine chemicals. Despite numerous established procedures for the reduction of nitro compounds, the development of catalytic methodologies that afford high chemoand regioselectivity under mild reaction conditions is still a challenging problem. As for the synthesis of secondary amines, the direct use of commercially available and inexpensive nitroarenes and alcohols as starting materials is highly attractive, especially when a single catalyst system could be employed. In this valuable one-pot multistep transformation, the alcohol may conceivably serve two possible functions: as the hydrogen source for nitro reduction and as the alkylating reagent based on the catalytic hydrogen transfer. Although excess alcohol is required to ensure the completion of the reaction (see the Supporting Information for possible reaction stoichiometries), the operational simplicity of such transformations may have practical advantages for a concise synthesis of N-substituted amines in a more straightforward manner. Compared to the great progress being made in the amination of amines with alcohols, there are scarcely available reports dealing with the direct amination of nitroarenes with alcohols. To date, only three Ru-based homogeneous systems have been reported. However, these homogeneous catalysts are problematic in terms of the recovery/ recycling of the catalyst and the necessity of special handling of metal complexes. From a sustainable point of view, a more efficient reaction with a ligand-free heterogeneous catalyst is highly desired. Over the last five years, we have been interested in the unique catalytic properties of supported gold nanoparticles (NPs) and involved in their application to sustainable organic synthesis. Recently, we have shown that very small Au NPs (approx. 1.8 nm) deposited on TiO2 (Au/TiO2-VS; VS=very small) acts as an efficient heterogeneous catalyst for the clean and atom-efficient mono-N-alkylation of a range of amines with alcohols in excellent yields under hydrogen-borrowing conditions. In view of the prominent efficiency of the gold system for the amination of amines with alcohols, we envisioned that the Au-mediated hydrogen-borrowing strategy could afford a green and efficient protocol for the direct amination of nitroarenes with alcohols under mild conditions. Herein, we report for the first time that the simple Au/TiO2-VS system can catalyze the selective secondary or tertiary amine formation from the direct condensation of nitroarenes and alcohols. Notably, the reaction can proceed effectively under ligandand basefree conditions without any external hydrogen resources. To the best of our knowledge, this study also forms the first report of a one-pot selective preparation of imines from nitroarenes and alcohols by using a heterogeneous gold-mediated “catalytic hydrogen-transfer” procedure. Based on our previous results in heterogeneous Au-catalyzed amine/alcohol coupling chemistry, the optimization study was initiated with the direct amination of nitrobenzene (1a) with eight equivalents of benzyl alcohol (2a) in the presence of Au/TiO2-VS (0.5 mol% of Au, see the Sup[a] C.-H. Tang, L. He, Dr. Y.-M. Liu, Prof. Dr. Y. Cao, Prof. Dr. H.-Y. He, Prof. K.-N. Fan Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials Department of Chemistry, Fudan University Shanghai 200433 (P.R. China) Fax: (+86)21-65643774 E-mail : yongcao@fudan.edu.cn Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201100393.