exo,syn-2-(hydroxy(4-nitrophenyl)methyl)-8-methyl-8-azabicyclo[3.2.1]octan-3-one

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: exo,syn-2-(hydroxy(4-nitrophenyl)methyl)-8-methyl-8-azabicyclo[3.2.1]octan-3-one
• 英文别名: (1R,2S,5S)-2-[(S)-hydroxy-(4-nitrophenyl)methyl]-8-methyl-8-azabicyclo[3.2.1]octan-3-one
• 化学式: C₁₅H₁₈N₂O₄
• 分子量: 290.319
• InChiKey: FNCVBADSOYVOML-CTHBEMJXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  86.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  exo,syn-2-(hydroxy(4-nitrophenyl)methyl)-8-methyl-8-azabicyclo[3.2.1]octan-3-one 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 6.0h， 生成 2E-(4-nitrobenzylidene)-8-methyl-8-azabicyclo[3.2.1]-octan-3-one
  参考文献：
  名称：

  The Preparation of 2‐Arylmethylidene‐8‐methyl‐8‐azabicyclo[3.2.1]octan‐3‐ones

  摘要：

  An efficient and versatile two-step synthesis of 2-arylmethylidene-8-methyl-8-azabicyclo[3.2.1]octane-3-ones, via mono aldol condensation of tropinone with a variety of aryl aldehydes followed by pTsOH-catalyzed dehydration, is described.

  DOI：

  10.1081/scc-120037905
• 作为产物：
  描述：

  托品酮 、 对硝基苯甲醛 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正庚烷 、 乙基苯 为溶剂， 反应 6.0h， 生成 exo,syn-2-(hydroxy(4-nitrophenyl)methyl)-8-methyl-8-azabicyclo[3.2.1]octan-3-one
  参考文献：
  名称：

  The Preparation of 2‐Arylmethylidene‐8‐methyl‐8‐azabicyclo[3.2.1]octan‐3‐ones

  摘要：

  An efficient and versatile two-step synthesis of 2-arylmethylidene-8-methyl-8-azabicyclo[3.2.1]octane-3-ones, via mono aldol condensation of tropinone with a variety of aryl aldehydes followed by pTsOH-catalyzed dehydration, is described.

  DOI：

  10.1081/scc-120037905

文献信息

• Environmentally benign diastereoselective synthesis of granatane and tropane aldol derivatives
  作者：Aneta Nodzewska、Agnieszka Bokina、Katarzyna Romanowska、Ryszard Lazny

  DOI：10.1039/c4ra02834a

  日期：——

  Direct aldol reactions of tropinone and granatanone (pseudopelletierine) with aromatic aldehydes were promoted by the presence of water. The anti–syn-diastereoselectivity depended on the amount of water used or on the possibility of product precipitation from the reaction mixture. Some of the reactions showed excellent atom economy, a low E factor, and high diastereoselectivity (up to 98%). In several cases ‘seeding’ with the anti isomer, used to induce the deposition of solid products, improved the conversion (up to 1.8 times) and the anti–syn ratio (up to 98 : 2). The applicability of spontaneous direct aldol reactions in the presence of water was also extended to N-alkyl nortropanones or norgranatanones using an aqueous–organic medium. However, under these conditions only the exo,syn isomers of the N-substituted aldols were obtained. The syn-selectivity for the tropane- and granatane-related aldols is specific for water-promoted reactions and results from thermodynamic control.

  水的存在促进了托品酮和石榴酮（伪派尔特利林）与芳香醛的直接 aldol 反应。反应的反对–顺代谢选择性取决于使用的水的量或反应混合物中产物沉淀的可能性。一些反应表现出优异的原子经济性、较低的 E 因素和高达 98% 的立体选择性。在几个案例中，使用反对异构体进行“引种”，以诱导固体产物的沉淀，提高了转化率（高达 1.8 倍）和反对–顺比（高达 98:2）。在水的存在下，自发直接 aldol 反应的适用性也扩展到了 N-烷基北托品酮或北石榴酮，采用水-有机介质。然而，在这些条件下，只获得了 N-取代的 aldol 的外，顺异构体。对于与托品和石榴相关的 aldol，顺选择性是水促进反应所特有的，源于热力学控制。
• A DFT study of the origins of the stereoselectivity in the aldol reaction of bicyclic amino ketones in the presence of water
  作者：Ryszard Lazny、Artur Ratkiewicz、Aneta Nodzewska、Joanna Wysocka

  DOI：10.1016/j.tetlet.2012.08.070

  日期：2012.10

  anti/syn-diastereomeric ratio (dr) for the solvent-less reaction of tropinone with several aromatic aldehydes. The CPCM-B3LYP/6-31g(d) method reproduces the anti/syn-diastereomeric ratio of the aqueous aldol reaction of tropinone with several aromatic aldehydes with reasonable deviation (0–88%), excellent (0–10)% agreement was found for the reactions of tropinone and granatanone with benzaldehyde. Qualitatively

  肌钙蛋白（8-甲基-8-氮杂双环[3.2.1] octan-3-one）和格拉纳酮（伪松油碱，9-甲基-9-氮杂双环[3.3.1]的直接无溶剂（纯）羟醛反应的实验非对映选择性。 ] nonan-3-one）在催化量的水的存在下，最精确地通过理论上B3LYP / 6-31g（d）的气相计算的异构体的热力学分布来精确再现。小于30％的系统误差，平均而言，存在于所预测的反/顺式-diastereomeric比（博士为托品酮的与几个芳族醛的无溶剂型反应）。CPCM-B3LYP / 6-31g（d）方法复制了anti / syn-肌钙蛋白与几种芳香族醛的水性羟醛反应的非对映体比率（合理偏差（0–88％），极好（0-10）％）被认为是肌钙蛋白和格拉纳坦酮与苯甲醛的反应。还发现在不同溶剂（DMF，THF和Et 3 N）中的dr值在质量上令人满意。密度泛函理论（DFT）的结果支持了反应热力学控制的概念。
• Spontaneous and diastereoselective aldol reactions of cyclic β-amino ketones in the presence of water
  作者：Ryszard Lazny、Aneta Nodzewska、Iwona Tomczuk

  DOI：10.1016/j.tetlet.2011.08.107

  日期：2011.10

  Direct aldol reactions of 4-methyl-1-piperidone, tropinone and granatanone (pseudopelletierine) take place spontaneously in the presence of water without any catalyst or additional reagents. The anti/syn-diastereoselectivity of the aqueous aldol reaction depends on the amount of water used. The syn-selectivity of the reaction is probably due to the thermodynamic control. Excellent atom economy and low E factors together with anti-selectivity as high as 98:2 for the tropinone aldol were obtained. (C) 2011 Elsevier Ltd. All rights reserved.
• The Preparation of 2‐Arylmethylidene‐8‐methyl‐8‐azabicyclo[3.2.1]octan‐3‐ones
  作者：Guangrong Zheng、Linda P. Dwoskin、Peter A. Crooks

  DOI：10.1081/scc-120037905

  日期：2004.12.31

  An efficient and versatile two-step synthesis of 2-arylmethylidene-8-methyl-8-azabicyclo[3.2.1]octane-3-ones, via mono aldol condensation of tropinone with a variety of aryl aldehydes followed by pTsOH-catalyzed dehydration, is described.