Transition-Metal-Catalyzed Alkylations of Amines with Alkyl Halides: Photoinduced, Copper-Catalyzed Couplings of Carbazoles
Transition-Metal-Catalyzed Alkylations of Amines with Alkyl Halides: Photoinduced, Copper-Catalyzed Couplings of Carbazoles
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DOI：
10.1002/anie.201301202
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发表时间：
2013-01-01
影响因子：
16.6
通讯作者：
Fu, Gregory C.
中科院分区：
文献类型：
--
作者：
Bissember, Alex C.;Lundgren, Rylan J.;Fu, Gregory C.
发展碳-氮键形成的新方法是有机化学的核心挑战，部分原因是含氮化合物倾向于表现出有趣的生物活性各种强有力的方法已经被设计出来，包括令人尊敬的过程，如还原性胺化[3]和Ullmann偶联[4,5]，以及最近发展起来的Buchwald-Hartwig反应[6]尽管这些过程很实用，但发现碳氮键形成的新方法仍然是一个重要的目标也许碳氮键构建最经典的“教科书”方法是胺与烷基卤化物的反应[式(1)]，这种转化在有机合成中继续发挥着关键作用由于这一过程通常遵循SN2途径，因此通常采用升高的反应温度来抑制未活化的初级和次级亲电试剂据我们所知，几乎没有这种方法的过渡金属催化变体的例子，这将使碳-氮键的形成在更温和的条件下进行。我们最近报道了咔唑与芳基卤化物的Ullmann C-N偶联可以在室温下通过光解完成（例如[Eq.(2)]）作为这一过程的机理研究的一部分，我们确定辐照铜-咔唑烷配合物1和碘化芳基2的混合物会导致环化偶联产物3（方案1）。产物中Csp3 ÀN键的形成给我们提供了开发的可能性
The development of new methods for the formation of carbon–nitrogen bonds is a central challenge in organic chemistry,[1] owing in part to the propensity of nitrogencontaining compounds to exhibit interesting bioactivity.[2] A variety of powerful approaches have been devised, including venerable processes such as reductive amination [3] and Ullmann coupling,[4, 5] as well as the more recently developed Buchwald–Hartwig reaction.[6] Despite the utility of such processes, the discovery of novel methods for the formation of carbon–nitrogen bonds remains an important objective.[7] Perhaps the most classic “textbook” approach to carbon–nitrogen bond construction is the reaction of an amine with an alkyl halide [Eq.(1)],[8] a transformation that continues to play a critical role in organic synthesis.[9] Because this process generally follows an SN2 pathway, elevated reaction temperatures are typically employed for hindered primary and secondary electrophiles that are unactivated.[1] To our knowledge, there are virtually no examples of transition-metalcatalyzed variants of this method, which would enable carbon–nitrogen bond formation to proceed under milder conditions.[10]We recently reported that Ullmann C–N couplings of carbazole with aryl halides can be accomplished at room temperature through photolysis (for example,[Eq.(2)]).[11] As part of a mechanistic investigation of this process, we determined that irradiation of a mixture of copper–carbazolide complex 1 and aryl iodide 2 leads to cyclized coupling product 3 (Scheme 1). The formation of a Csp3 ÀN bond in the product suggested to us that it might be possible to develop