Acceptorless Dehydrogenation of Nitrogen Heterocycles with a Versatile Iridium Catalyst
Acceptorless Dehydrogenation of Nitrogen Heterocycles with a Versatile Iridium Catalyst
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DOI：
10.1002/anie.201300292
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发表时间：
2013-01-01
影响因子：
16.6
通讯作者：
Xiao, Jianliang
中科院分区：
文献类型：
--
作者：
Wu, Jianjun;Talwar, Dinesh;Xiao, Jianliang
催化脱氢（CDH）是化学品生产中最重要的反应之一。[1]例如，每年由乙苯的CDH生产约1700万吨苯乙烯。然而，CDH在精细化学品、药物和农用化学品的合成中使用得少得多，尽管由于避免了化学计量的氧化剂，它在原子经济性和环境影响方面提供了相当大的益处。近年来，尽管经常使用牺牲氢受体和添加剂，但已经用金属络合物实现了烷烃、醇和胺的CDH。[2]然而，能够取代杂环的均相催化剂非常罕见，并且那些有活性的催化剂大多是非均相催化剂，其通常表现出差的官能度耐受性并且需要苛刻的反应条件。[3，4]最近，Fujita和Yamaguchi报道了使用[Cp* Ir（2-羟基吡啶）]催化剂进行四氢喹啉均相脱氢的第一个实例。[5]局限性在于，仅证明了几个1，2，3，4-四氢喹啉的实例，并且反应条件是相对强制性的[2摩尔%催化剂在对二甲苯（bp 1388 ℃）中20小时或在均三甲苯（bp 1658 ℃）中5小时]。鉴于含氮芳烃在许多天然生物碱和合成药物中的重要性，以及作为潜在的储氢材料，[6]开发具有更高CDH活性和更宽范围的单一催化体系将具有重大意义。我们最近报道了环化的[Cp* IrIII]/亚氨基配合物1是还原胺化的优良催化剂（方案1）。[7]它们在H2压力下或用甲酸盐处理时容易形成氢，并且可以在酸的帮助下产生H2。受Fujita工作的启发，我们设想当与胺反应时，1可以进行β-氢消除，从而在质子化时产生亚氨基键和H2。[8]测试1是否不仅可以用于四氢喹啉的CDH，而且也可以用于其他N-杂环的CDH，这将是有趣的。我们选择2-甲基-1，2，3，4-四氢喹啉（2a）作为模型底物进行研究。如预期的，在不存在催化剂的情况下，在回流2小时后，在2，2，2-三氟乙醇（TFE; bp 788 ℃）中未检测到2-甲基-喹啉（3a）的形成（表1，条目1）。在筛选了各种预催化剂和溶剂（条目2-19）之后，我们高兴地观察到，带有给电子OMe基团的配合物1d确实催化了TFE中2a的有效CDH，从而在2 h内提供88%的转化率。用0.1摩尔%过夜达到完全转化，沿着释放H2（条目7）。[9]其他络合物或溶剂的效果较差。
Catalytic dehydrogenation (CDH) is one of the most important reactions in the manufacturing of commodity chemicals.[1] For instance, annually approximately 17 million tons of styrene are produced by CDH of ethyl benzene. However, CDH has been much less used in the synthesis of fine chemicals, pharmaceuticals, and agrochemicals, although it offers considerable benefits with respect to atom economy and environmental impact because of the avoidance of stoichiometric oxidants. In recent years, CDH of alkanes, alcohols, and amines has been realized with metal complexes, although sacrificial hydrogen acceptors and additives are frequently used.[2] However, homogeneous catalysts capable of dehydrogenating heterocycles are very rare, and those catalysts that are active are mostly heterogeneous ones, which usually show poor functionality tolerance and require harsh reaction conditions.[3, 4] More recently, Fujita and Yamaguchi reported the first example of homogeneous dehydrogenation of tetrahydroquinolines using a [Cp* Ir (2-hydroxypyridine)] catalyst.[5] A limitation is that only a few examples of 1, 2, 3, 4-tetrahydroquinolines were demonstrated and the reaction conditions were relatively forcing [2 mol% catalyst for 20 h in refluxing p-xylene (bp 1388C) or 5h in mesitylene (bp 1658C)]. Given the importance of nitrogen-containing aromatics in numerous naturally occurring alkaloids and synthetic pharmaceuticals, and as potential hydrogen storage materials,[6] developing a single catalytic system with higher CDH activity and wider scope would be of significant interest. We recently reported that the cyclometalated [Cp* IrIII]/imino complexes 1 are excellent catalysts for reductive amination (Scheme 1).[7] They readily form hydrides under H2 pressure or when treated with formate, and could produce H2 with the aid of an acid. Inspired by the Fujita work, we envisioned that when reacted with an amine, 1 could undergo β-hydrogen elimination, thus generating an imino bond and H2 upon protonation.[8] It would be interesting to test if 1 could be exploited for the CDH of not only tetrahydroquinolines but other N-heterocycles as well. We started the investigation choosing 2-methyl-1, 2, 3, 4-tetrahydroquinoline (2a) as a model substrate. As expected, in the absence of a catalyst, formation of 2-methyl-quinoline (3a) was not detected in 2, 2, 2-trifluoroethanol (TFE; bp 788C) after 2 h at reflux (Table 1, entry 1). After screening a variety of precatalysts and solvents (entries 2–19), we were pleased to observe that complex 1d, which bears electrondonating OMe groups, did catalyze efficient CDH of 2a in TFE, thus furnishing 88% conversion in 2hours. Full conversion, along with release of H2, was reached with 0.1 mol% overnight (entry 7).[9] Other complexes or solvents were less effective.