Ruthenium-catalyzed oxidative cyanation of tertiary amines with hydrogen peroxide and sodium cyanide
Ruthenium-catalyzed oxidative cyanation of tertiary amines with hydrogen peroxide and sodium cyanide
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DOI：
10.1002/anie.200501496
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发表时间：
2005-01-01
影响因子：
16.6
通讯作者：
Terai, H
中科院分区：
文献类型：
--
作者：
Murahashi, SI;Komiya, N;Terai, H
近年来，人们对开发清洁和环境友好的方法将胺转化为相应的α-官能化化合物产生了很大的兴趣。这些化合物已被证明是多用途的中间体，并已被广泛用于构建生物活性氮化合物，如生物碱。[1]在叔胺的α位上直接引入取代基分两步进行：α-C3-OH活化生成亚胺鎓离子中间体，随后与亲核试剂反应。[2-4]最初的C2 H4活化已经通过两种方法实现，即通过氧化加成[2，5]用低价过渡金属或用金属-氧代物质。[2，3]虽然各种化合物可用于胺的氧化，但过氧化氢是满足最近环境和可持续需求的氧化剂，因为水是唯一的副产物。因此，人们广泛探索了用H2 O2催化氧化烯烃、醇、胺、硫化物和烷烃等底物的方法。[6，7]然而，在H2 O2氧化时将外部官能团引入基材的例子很少。[7r本文报道了在H_2O_2氧化条件下，叔胺的α位（相对于氮原子）上形成碳-碳键。因此，在氰化钠或氰化氢的存在下，叔胺与H2 O2的季铵盐催化的氧化氰化以高效率得到相应的α-氨基腈[Eq.①]。该反应是在H_2O_2氧化条件下C_2H直接活化和C_2C键形成的第一个例子，考察了在氰化钠存在下，N，N-二甲基苯胺与H_2O_2的氧化氰化反应的催化活性。RuCl 3被认为是最有效的催化剂。[RuCl 2（PPh 3）3]和Pr 4 N [RuO 4]表现出中等的催化活性，而K4 [Ru（CN）6]则阻碍了反应的进行。甲醇是最有效的溶剂，尽管也可以使用乙醇、乙酸乙酯和乙腈。加入乙酸对于与氰化钠的反应是必要的，否则不发生反应。如表1所示，在氰化钠存在下，各种叔胺可以用H2 O2有效地转化为相应的α-氨基腈[9]。带有供电子和吸电子取代基的取代的N，N-二甲基苯胺的反应得到相应的氰化产物（条目1-3）。在其他烷基存在下，N-甲基主要反应。例如，N-甲基-N-乙基苯胺的反应得到N-氰甲基-N-乙基苯胺（8）沿着少量的N-（1-氰乙基）-N-甲基苯胺（9;条目4）。该反应也可以有效地应用于环胺：三氢异喹啉，吡咯烷和四氢异喹啉衍生物可以转化为相应的α氰基胺（条目5-8）。就底物而言，使用H2 O2的氧化氰化比使用分子氧更通用;[10]例如，分子氧不能用于与哌啶和吡咯烷衍生物的反应。N-（4-甲氧基苯基）吡咯烷（14）与H2 O2的铼催化氧化氰化反应以80%的产率得到相应的α-氰化胺15（条目7），而与分子氧的相同反应仅以23%的产率得到产物。
There has been much interest in the development of clean and environmentally benign methods for the transformation of amines into the corresponding α-functionalized compounds. These compounds have proven to be versatile intermediates and have been widely used in the construction of biologically active nitrogen compounds such as alkaloids.[1] Direct introduction of a substituent at the α position of tertiary amines is performed in two steps: α-CÀH activation to produce iminium ion intermediates and subsequent reaction with nucleophiles.[2–4] The initial CÀH activation has been achieved by two methods, that is, with low-valent transition metals by oxidative addition [2, 5] or with metal–oxo species.[2, 3] Although various compounds can be used for the oxidation of amines, hydrogen peroxide is the oxidant that satisfies recent environmental and sustainable demands, because water is the sole by-product. Therefore, catalytic oxidation of substrates such as alkenes, alcohols, amines, sulfides, and alkanes with H2O2 has been explored extensively.[6, 7] However, there are few examples for the introduction of an external functional group to substrates upon H2O2 oxidation.[7r, 8] We report here that a carbon–carbon bond forms at the α position (with respect to the nitrogen atom) of tertiary amines under the H2O2 oxidation conditions. Thus, the ruthenium-catalyzed oxidative cyanation of tertiary amines with H2O2 in the presence of sodium cyanide or hydrogen cyanide gives the corresponding α-aminonitriles with high efficiency [Eq.(1)]. The reaction is, to the best of our knowledge, the first example of direct CÀH activation and CÀC bond formation under H2O2 oxidation conditions.The catalytic activity for the oxidative cyanation of N, N-dimethylaniline with H2O2 in the presence of sodium cyanide was examined. RuCl3 was found to be the most effective catalyst.[RuCl2 (PPh3) 3] and Pr4N [RuO4] show moderate catalytic activity, while K4 [Ru (CN) 6] retards the reaction. Methanol is the most effective solvent, although ethanol, ethyl acetate, and acetonitrile can also be used. The addition of acetic acid is necessary for the reaction with sodium cyanide, as otherwise no reaction takes place. As shown in Table1, various tertiary amines can be efficiently converted into the corresponding α-aminonitriles [9] with H2O2 in the presence of sodium cyanide. Reaction of substituted N, N-dimethylanilines bearing both electrondonating and electron-withdrawing substituents gave the corresponding cyanated products (entries 1–3). In the presence of other alkyl groups, the N-methyl group reacts predominantly. For example, the reaction of N-methyl-N-ethylaniline gave N-cyanomethyl-N-ethylaniline (8) along with a small amount of N-(1-cyanoethyl)-N-methylaniline (9; entry 4). The reaction can also be applied efficiently to cyclic amines: Piperidine, pyrrolidine, and tetrahydroisoquinoline derivatives can be converted into the corresponding αcyanoamines (entries 5–8). In terms of the substrate, oxidative cyanation with H2O2 is more versatile than with molecular oxygen;[10] for example, molecular oxygen cannot be used for reactions with piperidine and pyrrolidine derivatives. The ruthenium-catalyzed oxidative cyanation of N-(4-methoxyphenyl) pyrrolidine (14) with H2O2 gave the corresponding α-cyanated amine 15 in 80% yield (entry 7), while the same reaction with molecular oxygen provided the product in only 23% yield.