Electrochemical Allylation Reactions of Simple Imines in Aqueous Solution Mediated by Nanoscale Zinc Architectures
Electrochemical Allylation Reactions of Simple Imines in Aqueous Solution Mediated by Nanoscale Zinc Architectures
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纳米锌结构介导的水溶液中简单亚胺的电化学烯丙基化反应
DOI：
10.1002/anie.201004852
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发表时间：
2011-01-01
影响因子：
16.6
通讯作者：
Dong, Yi
中科院分区：
文献类型：
--
作者：
Huang, Jing-Mei;Wang, Xu-Xiao;Dong, Yi
高烯丙基胺是许多具有生物活性的化合物和含氮天然产物的重要结构单元，通过烯丙基金属试剂与C= N双键的加成反应是合成高烯丙基胺最重要、最直接的方法之一。[1]近年来，可以在水介质中进行的有机反应由于显著的环境和经济优势而引起了极大的兴趣，[2]特别是对于水介质中的Barbier型反应。[3]然而，由于简单亚胺的亲电性较低，在水中不稳定，大多数以前报道的金属介导的水性烯丙基化反应集中在使用特殊的亚胺，如磺酰亚胺，甲苯磺酰基或芳基腙，和乙醛肟醚。[4]这些报道的系统的有限范围鼓励我们寻找方法来实现简单的亚胺在水介质中的烯丙基化反应。电化学方法是另一种有效的有机转化和可持续化学的方法，[5，6]我们也对开发水溶液中的新电化学过程感兴趣。[7]本文报道了在饱和NH 4 Br水溶液和四氢呋喃（9：1）的混合溶液中，室温下锌离子介导的简单亚胺的电化学烯丙基化反应，该方法同样适用于简单亚胺的烷基化和苄基化反应.初始研究在室温下在0.1mLiClO4/四氢呋喃（9：1;表1，条目1）的中性水性条件下在单室电池中在恒定电流（30 mA）下进行，并且选择锌箔（各1.5cm 2）作为阳极和阴极。电解75分钟后，没有得到所需产物。在0.1 m NaOH溶液中观察到相同的结果（表1，条目2），而在酸性0.1 m HCl溶液中（表1，条目3），仅检测到痕量的所需产物。在0.1 m HOAc溶液和氨溶液（4.5 m）[7a]中，获得所需的高烯丙基胺，产率分别为< 5%和<15%（表1，条目4和5）。当使用铵盐时，结果更有希望（表1，条目6-8），并且发现NH 4 Br作为电解质盐上级NH 4Cl（92%产率）。减少四氢呋喃的量或使用甲醇代替导致较低的产率（表1，条目9和10）。对电流密度影响的研究（表1，条目11和12）表明，电流的增加或减少导致产率降低。当用铂电极进行电解时，没有发生烯丙基化（表1，条目13）。其他电极（铝和锡）显示出低收率（分别为10%和15%，表1，条目14和15）。因此，发现我们优化的反应条件是表1条目8中给出的那些。接下来，研究了各种简单亚胺，结果总结在表2中。芳族、杂芳族、脂肪族醛和芳族或脂肪族胺衍生的亚胺都是合适的底物，并以良好的产率产生相应的高烯丙基胺。这种温和的方法耐受包括甲氧基、氯、溴、羟基和氰基[8]的官能团。受上述结果的鼓舞，我们将该反应体系应用于手性亚胺，探索在水溶液中合成对映体富集的高烯丙基胺的新方法。通过使用衍生自l-缬氨酸甲酯、l-苯丙氨酸甲酯和l-苯基甘氨醇的亚胺，发现反应在室温下良好地进行。
Addition of allylmetal reagents to C= N double bonds is one of the most important and straightforward methods to afford homoallylic amines, which are useful building blocks for many biologically active compounds and nitrogen-containing natural products.[1] In recent years, organic reactions that can be performed in aqueous media have attracted great interest because of significant environmental and economical advantages,[2] especially for the Barbier-type reactions in aqueous media.[3] However, owing to the lower electrophilicity of simple imines and their instability in water, most of the previously reported metal-mediated aqueous allylation reactions were focused on the use of special imines, such as sulfonimines, tosyl or aryl hydrazones, and glyoxylic oxime ethers.[4] The limited scope of these reported systems encourages us to search for methods to achieve the allylation reactions of simple imines in aqueous media. Electrochemical methods are another approach to efficient organic transformations and sustainable chemistry,[5, 6] and we have also been interested in developing new electrochemical process in aqueous solution.[7] Herein, we reported a zinc-mediated electrochemical allylation reaction of simple imines in a mixture of saturated aqueous NH4Br and tetrahydrofuran (9: 1) at room temperature; this method is also suitable for the alkylation and benzylation of simple imines. Initial studies were performed at room temperature under neutral aqueous conditions of 0.1 m LiClO4/tetrahydrofuran (9: 1; Table 1, entry 1) in a one-compartment cell under a constant current (30 mA), and zinc foils (1.5 cm2 each) were chosen as both the anode and cathode. After electrolysis for 75 minutes, none of the desired product was obtained. The same result was observed in 0.1 m NaOH solution (Table 1, entry2), whilst in an acidic 0.1 m HCl solution (Table1, entry 3), only a trace amount of the desired product was detected. In 0.1 m HOAc solution and ammonia solution (4.5 m)[7a], the desired homoallylic amine was obtained with yields of< 5% and< 15%, respectively (Table 1, entries 4 and 5). When ammonium salts were employed, the results were more promising (Table 1, entries 6–8), and NH4Br was found to be superior (92% yield) to NH4Cl as an electrolyte salt. Reducing the amount of the tetrahydrofuran or using methanol instead resulted in lower yields (Table 1, entries 9 and 10). Studies on the effect of current density (Table 1, entries 11 and 12) showed that an increase or decrease of the current resulted in a decrease in the yield. No allylation occurred when the electrolysis was carried out with platinum electrodes (Table 1, entry 13). Other electrodes (aluminium and tin) showed low yields (10% and 15%, respectively, Table 1, entries 14 and 15). Therefore, our optimized reaction conditions were found to be those given in Table 1, entry 8. Next, a wide variety of simple imines were investigated, and the results are summarized in Table 2. Imines derived from aromatic, heteroaromatic, aliphatic aldehydes, and aromatic or aliphatic amines were all suitable substrates and produced the corresponding homoallylic amines in good yields. The functionalities including methoxyl, chloro, bromo, hydroxy, and cyano [8] were tolerated by this mild method. Encouraged by the above results, we applied this reaction system to chiral imines to explore a new method for the synthesis of enantiomerically enriched homoallylic amines in aqueous solution. By using the imines derived from l-valine methyl ester, l-phenylalanine methyl ester, and l-phenylglycinol, it was found that the reaction worked well in the