2-(2-methoxyphenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione | 93465-44-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 2-(2-methoxyphenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione
• 英文别名: (1R,2S,6R,7S)-4-(2-Methoxy-phenyl)-4-aza-tricyclo[5.2.1.0^2,6]dec-8-ene-3,5-dione；(1R,2S,6R,7S)-4-(2-methoxyphenyl)-4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione
• CAS: 93465-44-2
• 化学式: C₁₆H₁₅NO₃
• 分子量: 269.3
• InChiKey: XRULRZXSODUQHB-IOQCUFBNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(2-methoxyphenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 在 硫酸 、 双氧水 、 溶剂黄146 、 水 作用下， 以 水 为溶剂， 反应 3.0h， 以83%的产率得到(1S,2S,6R,7R,8S,9S)-8,9-dihydroxy-4-(2-methoxyphenyl)-4-azatricyclo[5.2.1.02,6]decane-3,5-dione
  参考文献：
  名称：

  Stereochemistry of dihydroxylation of N-arylbicyclo[2.2.1]-hept-5-ene-endo- and -exo-2,3-dicarboximides

  摘要：

  Stereochemistry of the oxidation of N-arylbicyclo[2.2.1]hept-5-ene-endo-and-exo-2,3-dicarboximides at the double bond with peroxyacetic acid generated in situ in the presence of sulfuric acid and with an anhydrous dioxane solution of peroxyacetic acid was studied. In both cases, the reaction was stereospecific, regardless of the substituent in the N-aryl group and configuration of the imide ring, but the reaction direction depended on the presence of water in the system. In the first case, the corresponding trans-5,6-dihydroxy derivatives were formed, while in the second, exo-5,6-epoxy derivatives. The oxidation of N-arylbicyclo[2.2.1]-hept-5-ene-endo-and-exo-2,3-dicarboximides with a solution of potassium permanganate in aqueous acetone gave the corresponding N-aryl-cis-5,6-dihydroxybicyclo[2.2.1]heptane-endo-and-exo-2,3-dicarboximides. The exo,cis,exo and exo,cis,endo configurations of the synthesized compounds were determined by H-1 NMR spectroscopy.

  DOI：

  10.1134/s1070428007110097
• 作为产物：
  描述：

  (1R,2S,3R,4S)-3-[(2-methoxyphenyl)carbamoyl]bicyclo[2.2.1]hept-5-ene-2-carboxylic acid 反应 16.0h， 以0.12 g的产率得到2-(2-methoxyphenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione
  参考文献：
  名称：

  A Molecular Balance for Measuring Aliphatic CH−π Interactions

  摘要：

  A series of conformationally flexible bicyclic N-arylimides were employed as molecular balances to study the weak aliphatic CH-pi Interaction between alkyl and arene groups. The formation of intramolecular CH-pi interactions in the folded conformers was characterized by X-ray crystallography. The strengths of the interactions were characterized in CDCl(3) by the changes in the folded/unfolded ratios, as measured by (1)H NMR. The CH-pi interaction between a methyl group and an aromatic surface was similar to 1.0 kcal/mol and was easily disrupted or masked by conformational entropy and repulsive steric Interactions.

  DOI：

  10.1021/ol201657p
• 作为试剂：
  描述：

  1-[2-(Bromomethyl)phenyl]indole 、 S-p-tolyl 2-methylthiophene-3-carbothioate 在 copper(I) oxide 、 potassium dihydrogenphosphate 、 三(2-呋喃基)膦 、 palladium diacetate 、 2-(2-methoxyphenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 作用下， 以 乙腈 为溶剂， 以64 %的产率得到13-methyl-10H-benzo[6,7]thieno[3',4':3,4]azepino[1,2-a]indole
  参考文献：
  名称：

  通过串联 Pd/NBE 催化脱羰和双 C-H 激活序列构建吲哚稠合七元和八元氮杂环

  摘要：

  在此，我们报道了芳香酸向吲哚稠合的七元和八元氮杂环的转化。两个C-C键是通过一个C-C键和两个C-H键裂解形成的。将吲哚部分掺入生物活性药物和天然产物中以构建中等大小的多稠合杂环，证明了该方案的合成效用。

  DOI：

  10.1021/acs.orglett.3c01579

文献信息

• Large transition state stabilization from a weak hydrogen bond
  作者：Erik C. Vik、Ping Li、Josef M. Maier、Daniel O. Madukwe、Vitaly A. Rassolov、Perry J. Pellechia、Eric Masson、Ken D. Shimizu

  DOI：10.1039/d0sc02806a

  日期：——

  A series of molecular rotors was designed to study and measure the rate accelerating effects of an intramolecular hydrogen bond. The rotors form a weak neutral O–H⋯OC hydrogen bond in the planar transition state (TS) of the bond rotation process. The rotational barrier of the hydrogen bonding rotors was dramatically lower (9.9 kcal mol−1) than control rotors which could not form hydrogen bonds. The

  设计了一系列分子转子，以研究和测量分子内氢键的加速作用。转子在键旋转过程的平面过渡状态（TS）中形成弱的中性O–H⋯O C氢键。氢键转子的旋转势垒比不能形成氢键的控制转子低得多（9.9 kcal mol -1）。稳定的幅度明显大于根据类似的O–H⋯O C氢键（1.5 kcal mol -1）的独立测量强度所预测的值。大过渡态稳定的起源是通过实验性取代基效应和计算扰动分析。氢键相互作用的能量分解分析表明，氢键相互作用的斥力成分显着降低。分子转子的刚性框架在过渡态中定位并预组织了相互作用的基团。这项研究表明，通过适当的设计，单个氢键可以导致大于固有相互作用能的TS稳定化，这在催化剂设计和酶机理研究中具有应用。
• Transition-State Stabilization by n→π* Interactions Measured Using Molecular Rotors
  作者：Erik C. Vik、Ping Li、Perry J. Pellechia、Ken D. Shimizu

  DOI：10.1021/jacs.9b08542

  日期：2019.10.23

  A series of 16 molecular rotors were synthesized to investigate the ability of n→π* interactions to stabilize transition states (TS) of bond rotation. Steric contributions to the rotational barrier were isolated using control rotors, which could not form n→π* interactions. Rotors with strong acceptor π* orbitals such as ketones, aldehydes, and nitriles had greatly increased rates of rotation. The TS

  合成了一系列 16 个分子转子以研究 n→π* 相互作用稳定键旋转过渡态 (TS) 的能力。使用无法形成 n→π* 相互作用的控制转子隔离对旋转屏障的空间贡献。具有强受体 π* 轨道（如酮、醛和腈）的转子的旋转速率大大提高。高达 ~10 kcal/mol 的 TS 稳定性与在平面 TS 中酰亚胺羰基氧和邻-R 基团之间形成强的 n→π* 稳定性是一致的。计算研究有效地模拟了 TS 的稳定性和几何形状，NBO 分析证实了 n→π* 相互作用在稳定 TS 中的作用。
• <i>meta</i>‐C−H Arylation of Aniline Derivatives via Palladium/ S,O‐Ligand/Norbornene Cooperative Catalysis
  作者：Verena Sukowski、Manuela van Borselen、Simon Mathew、Bas de Bruin、M. Ángeles Fernández‐Ibáñez

  DOI：10.1002/anie.202317741

  日期：2024.1.25

  Aromatic amines are ubiquitous moieties in organic molecules and their direct functionalization is of great interest in many research areas due to their prevalence in pharmaceuticals and organic electronics. While several synthetic tools exist for the ortho‐ and para‐functionalization of anilines, the functionalization of the less reactive meta‐position is not easy to achieve with current methods. To date, the meta‐C−H arylation of aniline derivatives has been restricted to either the use of directing groups & templates, or their transformation into anilides & quaternary anilinium salts. Herein, we report the first general and efficient meta‐C−H‐arylation of non‐directed aniline derivatives via cooperative catalysis with a palladium–S,O‐ligand–norbornene system. The reaction proceeds under mild conditions with a wide range of aniline derivatives and aryl iodides, while being operationally simple and scalable. Our preliminary mechanistic investigation–including the isolation of several palladium complexes and deuterium experiments–reveal useful insights into the substituent‐effects of both the aniline‐substrate and the norbornene‐mediator during the meta‐C−H activation step.

  摘要 芳香胺是有机分子中无处不在的分子，由于芳香胺在医药和有机电子产品中的广泛应用，其直接官能化在许多研究领域都引起了极大的兴趣。虽然有多种合成工具可以实现苯胺的正官能化和对官能化，但目前的方法却难以实现反应性较低的元位的官能化。迄今为止，苯胺衍生物的元-C-H 芳基化仅限于使用定向基团和模板，或将其转化为苯胺类和季胺盐。在此，我们首次报道了通过钯-S,O-配体-降冰片烯体系的协同催化，对非定向苯胺衍生物进行通用而高效的元-C-H-芳基化反应。该反应在温和的条件下进行，适用于多种苯胺衍生物和芳基碘化物，同时操作简单、规模可控。我们的初步机理研究--包括分离几种钯配合物和氘实验--揭示了在元-C-H 活化步骤中苯胺底物和降冰片烯介质的取代效应。
• Verma, S. M.; Verma, Ashok K., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1984, vol. 23, # 7, p. 639 - 642
  作者：Verma, S. M.、Verma, Ashok K.

  DOI：——

  日期：——
• ——
  作者：M. S. Salakhov、M. I. Bagmanova

  DOI：10.1023/a:1015573902465

  日期：——

  Epoxidation of endo- and evo-bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic acid N-arylimides with a solution of peracetic acid in anhydrous dioxane affords 5,6-exo-epoxybicycloheptanedicarboxylic acid N-arylimides. The epoxidation reaction is not sensitive to the configuration of the imide fragment, to the character and position of the substituent in the aromatic ring. The reaction is determined only by oxidation conditions.