2-deutero-1-methylindole | 857380-47-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-deutero-1-methylindole
• 英文别名: 1-methyl-1H-indole-2-d；2-Deuterio-1-methylindole
• CAS: 857380-47-3
• 化学式: C₉H₉N
• 分子量: 132.169
• InChiKey: BLRHMMGNCXNXJL-WHRKIXHSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  4.9
• 氢给体数：
  0
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  2-deutero-1-methylindole 在 potassium tert-butylate 作用下， 以 四氢呋喃 、 氘代四氢呋喃 为溶剂， 反应 376.5h， 生成 1-methyl-3-triethylsilylindole
  参考文献：
  名称：

  叔丁醇钾催化杂芳族化合物的脱氢CH-H硅烷化反应：实验与计算机理相结合的研究

  摘要：

  我们最近报道了一种利用地球上丰富的叔丁醇钾直接将杂芳烃进行CH-H甲硅烷基化的新方法。在这里，我们报告了这种转化的系统的实验和计算机制研究。我们的实验结果与自由基链机制一致。三烷基甲硅烷基自由基可能最初是通过红外检测到的超配位硅物种的弱Si-H键的均相裂解而产生的，或者是通过与[KO t -Bu] 4反应可产生反应性过氧化物的微量氧而产生的。如密度泛函理论（DFT）计算所示。自由基钟和动力学同位素实验支持一种机制，其中C-Si键是通过将甲硅烷基加成到杂环上，然后进行随后的β-氢断裂而形成的。DFT计算揭示了基本机理的合理能量分布，并支持了实验观察到的区域选择性。显示出甲硅烷基化反应是可逆的，由于H 2气体的产生，平衡有利于产物。使用氘代底物的原位NMR实验表明，H 2是通过交叉脱氢机理形成的。使用2对硅中心的立体化学过程进行了研究H标记的硅环烷探针; 在硅中心观察到完全加扰，这与许多可能的自由基中间体或超配位硅酸盐一致。

  DOI：

  10.1021/jacs.6b13031
• 作为产物：
  描述：

  1-methyl-3-deuterio-1H-indole 在 正丁基锂 、 palladium(II) trifluoroacetate 、 溶剂黄146 作用下， 以 四氢呋喃 、 二氧六环-d8 为溶剂， 生成 2-deutero-1-methylindole
  参考文献：
  名称：

  Cross-Dehydrogenative Couplings between Indoles and β-Keto Esters: Ligand-Assisted Ligand Tautomerization and Dehydrogenation via a Proton-Assisted Electron Transfer to Pd(II)

  摘要：

  Cross-dehydrogenative coupling reactions between beta-ketoesters and electron-rich arenes, such as indoles, proceed with high regiochemical fidelity with a range of beta-ketoesters and indoles. The mechanism of the reaction between a prototypical beta-ketoester, ethyl 2-oxocyclopentanonecarboxylate, and N-methylindole has been studied experimentally by monitoring the temporal course of the reaction by H-1 NMR, kinetic isotope effect studies, and control experiments. DFT calculations have been carried out using a dispersion-corrected range-separated hybrid functional (omega B97X-D) to explore the basic elementary steps of the catalytic cycle. The experimental results indicate that the reaction proceeds via two catalytic cycles. Cycle A, the dehydrogenation cycle, produces an enone intermediate. The dehydrogenation is assisted by N-methylindole, which acts as a ligand for Pd(II). The computational studies agree with this conclusion, and identify the turnover-limiting step of the dehydrogenation step, which involves a change in the coordination mode of the beta-keto ester ligand from an O,O'-chelate to an beta'-bound Pd enolate. This ligand tautomerization event is assisted by the if-bound indole ligand. Subsequent scission of the beta'-C-H bond takes place via a proton-assisted electron transfer mechanism, where Pd(II) acts as an electron sink and the trifluoroacetate ligand acts as a proton acceptor, to produce the Pd(0) complex' of the enone intermediate. The coupling is completed in cycle B, where the enone is coupled with indole. Pd(TFA)(2) and TFA-catalyzed pathways were examined experimentally and computationally for this cycle, and both were found to be viable routes for the coupling step.

  DOI：

  10.1021/ja501681y

文献信息

• Site-Selective Copper-Catalyzed Amination and Azidation of Arenes and Heteroarenes via Deprotonative Zincation
  作者：Charles E. Hendrick、Katie J. Bitting、Seoyoung Cho、Qiu Wang

  DOI：10.1021/jacs.7b07661

  日期：2017.8.23

  effective for a wide range of arenes, including nonactivated arenes bearing simple functionalities such as fluoride, chloride, ester, amide, ether, nitrile, and trifluoromethyl groups as well as heteroarenes including indole, thiophene, pyridine, and isoquinoline. An analogous C-H azidation is also accomplished using azidoiodinane for direct introduction of a useful azide group onto a broad scope of arenes

  芳烃胺化是通过位点选择性 CH 锌化，然后在温和条件下铜催化与 O-苯甲酰羟胺偶联来实现的。这一成功的关键是由氨基二乙基锌酸锂介导的邻位锌化，它对多种芳烃有效，包括带有简单官能团的非活化芳烃，如氟化物、氯化物、酯、酰胺、醚、腈和三氟甲基以及杂芳烃包括吲哚、噻吩、吡啶和异喹啉。类似的 CH 叠氮化也可以使用叠氮碘来完成，将有用的叠氮基团直接引入到广泛的芳烃和杂芳烃上。这些新的转化提供了快速获得有价值且多样化的氨基芳烃化学空间的途径。通过后期胺化和叠氮化反应合成天然产物 (-)-尼古丁和抗抑郁药舍曲林的新型类似物，证明了它们在有机合成和药物发现中的广泛应用。
• General and Practical Potassium Methoxide/Disilane-Mediated Dehalogenative Deuteration of (Hetero)Arylhalides
  作者：Xin Wang、Ming-Hui Zhu、David P. Schuman、Dayou Zhong、Wen-Yan Wang、Lin-Yang Wu、Wei Liu、Brian M. Stoltz、Wen-Bo Liu

  DOI：10.1021/jacs.8b07597

  日期：2018.9.5

  Herein we describe a general, mild and scalable method for deuterium incorporation by potassium methoxide/hexamethyldisilane-mediated dehalogenation of arylhalides. With CD3CN as a deuterium source, a wide array of heteroarenes prevalent in pharmaceuticals and bearing diverse functional groups are labeled with excellent deuterium incorporation (>60 examples). The ipso-selectivity of this method provides

  在此，我们描述了一种通过甲醇钾/六甲基乙硅烷介导的芳基卤化物脱卤来掺入氘的通用、温和且可扩展的方法。以 CD3CN 作为氘源，广泛存在于药物中并具有不同官能团的杂芳烃被标记为具有优异的氘掺入（> 60 个例子）。这种方法的 ipso 选择性提供了对氘代吲哚和喹啉库的精确访问。我们方法的合成效用已通过将氘掺入复杂的天然和类药物化合物中得到证明。
• Electrochemical C−H Amidation of Heteroarenes with<i>N</i>‐Alkyl Sulfonamides in Aqueous Medium
  作者：Yan Zhang、Zhipeng Lin、Lutz Ackermann

  DOI：10.1002/chem.202004229

  日期：2021.1.4

  The construction of C−N bonds by free radical reactions represents a powerful synthetic approach for direct C−H amidations of arenes or heteroarenes. Developing efficient and more environmentally friendly synthetic methods for C−H amidation reactions remains highly desirable. Herein, metal‐free electrochemical oxidative dehydrogenative C−H amidations of heteroarenes with N‐alkylsulfonamides have been

  通过自由基反应构建C-N键代表了对芳烃或杂芳烃直接C-H酰胺化的强大合成方法。为CH酰胺化反应开发高效且对环境友好的合成方法仍然是非常可取的。在此，杂芳烃与N-烷基磺酰胺的无金属电化学氧化脱氢CHH酰胺化反应已经完成。不含催化剂和化学氧化剂的CHH酰胺化反应范围广，并使用电作为绿色和唯一的氧化剂。各种杂芳烃，包括吲哚，吡咯，苯并呋喃和苯并噻吩，都经过了这种C（sp 2）-H氮化。循环伏安法研究和控制实验为无金属电催化直接生成以氮为中心的自由基提供了证据。
• Double Gold-Catalysed Annulation of Indoles by Enynones
  作者：Stephen J. Heffernan、James P. Tellam、Marine E. Queru、Andrew C. Silvanus、David Benito、Mary F. Mahon、Alan J. Hennessy、Benjamin I. Andrews、David R. Carbery

  DOI：10.1002/adsc.201300018

  日期：2013.4.15

  The gold‐catalysed double functionalisation of indoles is presented. Enynones are used to annulate indoles via a double sodium tetrachloroaurate‐catalysed process involving a mixture of CH activation and alkyne activation modes of promotion. Good yields for the formation of medicinally relevant [6,5,7]‐tricyclic indoles are realised.

  介绍了金催化的吲哚双官能化。Enynones用于有环的吲哚通过涉及℃的混合物中的双钠四氯催化过程 ħ激活和促进炔激活模式。实现了与医学相关的[6,5,7]-三环吲哚的良好生成。
• Nickel-Catalyzed Regioselective C(2)−H Difluoroalkylation of Indoles with Difluoroalkyl Bromides
  作者：Vineeta Soni、Dipesh M. Sharma、Benudhar Punji

  DOI：10.1002/asia.201800504

  日期：2018.9.4

  Regioselective C(2)−H difluoroalkylation of C‐3 unsubstituted indoles with commonly available fluoroalkyl bromides is successfully achieved employing a simple nickel catalyst system, (DME)NiCl2/Xantphos. This methodology shows excellent regioselectivity and exhibits a broad substrate scope. Various functional groups, such as ‐OMe, ‐F, and ‐Br, are tolerated on the indole backbone to give the difluoroalkylated

  使用简单的镍催化剂体系（DME）NiCl 2 / Xantphos成功地实现了C-3未取代的吲哚与常用的氟代烷基溴的区域选择性C（2）-H二氟烷基化。该方法显示出极好的区域选择性，并显示出较宽的底物范围。在吲哚主链上可以耐受各种官能团，例如OMe，-F和-Br，从而以中等至良好的收率得到二氟烷基化产物。初步的机理发现表明，该反应本质上是均相的，并且涉及自由基。合成褪黑激素受体拮抗剂Luzindole衍生物证明了这种镍催化方法的合成效用。