An Easy and General Iron-catalyzed Reductive Amination of Aldehydes and Ketones with Anilines
An Easy and General Iron-catalyzed Reductive Amination of Aldehydes and Ketones with Anilines
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DOI：
10.1002/asia.201100462
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发表时间：
2011-09-05
影响因子：
4.1
通讯作者：
Beller, Matthias
中科院分区：
文献类型：
--
作者：
Fleischer, Steffen;Zhou, Shaolin;Beller, Matthias
烷基化苯胺在食品、制药、农化、染料和聚合物工业中有着广泛的应用一般来说，工业上可用的苯胺与醛和酮的缩合以及随后的氢化反应是合成苯胺的一种直接方法。虽然在过去的二十年里，已经开发出了高选择性催化还原亚胺的方法，但不幸的是，在这些方法中，亚胺必须在一个额外的步骤中合成和分离。因此，醛和酮的还原性胺化反应是一种更有效和直接的合成途径过去，这条路线使用了还原剂，包括异丙醇、[4]甲酸酯、[5]和所谓的Hanztsch酯、[6]以及硅烷显然，最经济、最环保的方法是使用氢分子来进行还原步骤，而水是整个转化过程中唯一的副产品。大多数已知的用于后一种还原胺化反应的催化剂是基于铑、铱和钌的贵金属配合物由于这些贵金属及其相应的配合物的价格相对较高，寻找更经济和环境友好的催化剂是一个持续和具有挑战性的研究课题。在这方面，基于铁、铜、锌或锰的新型催化剂提供了特别有吸引力的选择虽然铁是地壳中含量第二丰富的金属，但人们对它的还原性研究却很少最近，Enthaler表明，使用硅烷，用简单的FeCl3可以进行醛的还原胺化值得注意的是，铁羰基配合物Fex (CO) y在烯烃的硅氢化反应和酰胺的还原反应中具有活性基于这些结果和我们在铁催化下还原C= X键的经验，[13c， 14]我们开始研究羰基化合物在铁催化剂存在下的还原胺化反应。因此，本文报道了廉价的Fe3 (CO) 12作为一种方便的均相催化剂体系，它允许在温和条件下使用分子氢进行醛和酮的还原胺化反应。在探索性研究中，在50bar氢压力和658C条件下，对4-甲氧基苯乙酮1a和4-茴香胺2a的模型反应进行了不同铁源的测试。将分子筛添加到反应混合物中，通过除去冷凝步骤中形成的水，将平衡向原位生成的亚胺转移。如表1所示，铁（II）和铁achtungtrennung （III）盐以及[Fe-ACHTUNGTRENNUNG (cot)(CO) 3]在模型反应中没有表现出任何活性（表1，条目2-6）；在这些铁盐和配合物存在的情况下，只形成相应的亚胺。令人惊讶的是，其他铁羰基配合物在模型反应中显示出显著的活性（表1，条目7 - 9）。由于Fe3 (CO) 12是最活跃的前驱体，因此用该配合物测试了不同的催化剂负载（表1，条目9-12）。让我们高兴的是，将催化剂负载从1 mol%增加到4 mol%，产率从29%提高到84%。接下来，在模型系统中考察了反应温度的影响（表1，条目11、13、14）。在358℃和1008℃时，只观察到低产量（分别为9%和40%）。在这两种情况下，预成型亚胺的还原都不完全，这可以解释为还原催化剂活性低（358C）或部分分解（1008C）。溶剂的变化表明，甲苯是较好的溶剂。
Alkylated anilines are used for a variety of applications in the food, pharmaceutical, agrochemical, dye, and polymer industries.[1] In general, the condensation of industrially available anilines with aldehydes and ketones and subsequent hydrogenation constitutes a straightforward approach for their synthesis. Although during the last two decades procedures for the highly selective catalytic reduction of imines have been developed,[2] unfortunately in these procedures the imine has to be synthesized and isolated in an additional step. Thus, the reductive amination of aldehydes and ketones constitutes a more efficient and direct route for their synthesis.[3] In the past, this route has employed reducing agents, including iso-propanol,[4] formates,[5] and socalled Hanztsch esters,[6] as well as silanes.[7] Clearly, the most atom economic and environmentally friendly approach is the use of molecular hydrogen [8] for the reduction step with water as the only side-product in the overall transformation. The majority of the known catalysts for the latter reductive aminations are based on precious metal complexes of rhodium, iridium, and ruthenium.[9] Owing to the comparably high price of these precious metals and their corresponding complexes, the search for more economical and environmentally friendly catalysts is an ongoing and challenging research topic. In this respect, novel catalysts based on iron, copper, zinc, or manganese offer particularly attractive options.[10] Although iron is the second most abundant metal in the earth’s crust, it has only been scarcely investigated for reductive aminations.[11] More recently, Enthaler showed that a reductive amination of aldehydes is possible with simple FeCl3 using silanes.[12] Notably, iron-carbonyl complexes Fex (CO) y were found to be active in the hydrosilylation of alkenes and the reduction of amides.[13] Based on these results and our experience in iron-catalyzed reductions of C= X bonds,[13c, 14] we started to investigate the reductive amination of carbonyl compounds in the presence of iron catalysts. As a result, herein, we report inexpensive Fe3 (CO) 12 as a convenient homogeneous catalyst system which allows for the reductive amination of aldehydes and ketones under mild conditions using molecular hydrogen. In exploratory studies, different iron sources were tested in the model reaction of 4-methoxyacetophenone 1a and 4-anisidine 2a at 50 bar hydrogen pressure and 658C. Molecular sieves were added to the reaction mixture to shift the equilibrium towards the in situ generated imine by removing water, which is formed during the condensation step. As shown in Table 1, iron (II)-and ironACHTUNGTRENNUNG (III)-salts as well as [Fe-ACHTUNGTRENNUNG (cot)(CO) 3] did not show any activity in the model reaction (Table 1, entries 2–6); in the presence of these iron salts and complexes, only the corresponding imine was formed. Surprisingly, other iron-carbonyl complexes showed significant activity in the model reaction (Table1, entries7–9). As Fe3 (CO) 12 turned out to be the most-active precursor, different catalyst loadings were tested with this complex (Table 1, entries 9–12). To our delight, the yield raised from 29% to 84% by increasing the catalyst loading from 1 to 4 mol%. Next, the influence of the reaction temperature was investigated in the model system (Table 1, entries 11, 13, 14). At 358C and 1008C, only low yields (9 and 40%, respectively) were observed. In both cases, the reduction of the preformed imine was not complete, which can be explained by either low activity (358C) or partial decomposition (1008C) of the reduction catalyst.Variation of the solvent showed that toluene is superior …