exo,syn-2-(hydroxy(phenyl)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(phenyl)methyl)-8-methyl-8-azabicyclo-[3.2.1]octan-3-one
• 英文别名: exo,syn-2-[hydroxy(phenyl)methyl]-8-methyl-8-azabicyclo[3.2.1]octan-3-one；(1R,2S,5S)-2-[(S)-hydroxy(phenyl)methyl]-8-methyl-8-azabicyclo[3.2.1]octan-3-one
• 化学式: C₁₅H₁₉NO₂
• 分子量: 245.321
• InChiKey: UMMPSTHTHNNUDH-CTHBEMJXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 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：
  40.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  exo,syn-2-(hydroxy(phenyl)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-benzylidene-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 、 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(phenyl)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。
• Solvent-Free Synthesis of a Secondary N-Benzhydrylamine as a Chiral Reagent for Asymmetric Deprotonation of Bicyclic N-Benzylamino Ketones
  作者：Aneta Nodzewska、Katarzyna Sidorowicz、Michal Sienkiewicz

  DOI：10.1055/s-0033-1340955

  日期：——

  (68–92%) without racemization by the direct alkylation of amines with benzhydryl chloride under solvent-free conditions. Using the solvent-free conditions (R)-N-benzhydryl-1-phenylethylamine was obtained with the highest yield (92%), purified on ion-exchange resin, and converted to its hydrochloride salt. The resulting chiral amine hydrochloride was transformed into lithium amide/lithium chloride mixture used

  摘要 通过在无溶剂条件下将胺与二苯甲基氯直接烷基化，可以合成高收率（68-92％）的数种手性仲N-苯甲胺，而不会发生外消旋作用。在无溶剂条件下（R），以最高收率（92％）获得N-苯甲酰基-1-苯基乙胺，在离子交换树脂上纯化，并转化为其盐酸盐。将所得的手性胺盐酸盐转化为酰胺化锂/氯化锂混合物，用于对肌钙蛋白和格拉他酮的N-苄基类似物进行不对称去质子化，然后进行醛醇缩合反应，得到高非对映体纯度（最高96％）和对映体过量77至96 ％。 通过在无溶剂条件下将胺与二苯甲基氯直接烷基化，可以合成高收率（68-92％）的数种手性仲N-苯甲胺，而不会发生外消旋作用。在无溶剂条件下（R），以最高收率（92％）获得N-苯甲酰基-1-苯基乙胺，在离子交换树脂上纯化，并转化为其盐酸盐。将所得的手性胺盐酸盐转化为酰胺化锂/氯化锂混合物，用于对肌钙蛋白和格拉他酮的N-苄基类似物进行不对称去质子化，然后进行醛醇缩合反
• Determination of the relative configuration of tropinone and granatanone aldols by using TBDMS ethers
  作者：Ryszard Lazny、Aneta Nodzewska、Katarzyna Sidorowicz、Przemyslaw Kalicki

  DOI：10.3762/bjoc.8.216

  日期：——

  diastereomers (exo,anti to endo,syn and exo,syn to endo,anti). The exo forms invert to endo isomers in the presence of silica gel. The relative configuration of a new isomer of tropinone aldol accessible synthetically through the direct solventless reaction of tropinone and benzaldehyde in the presence of water was determined as exo,syn by comparison of NMR data of the aldol isomers, in particular vicinal coupling

  托品酮醛醇（8-甲基-8-氮杂双环[3.2.1]辛烷-3-酮）的所有四种非对映异构体的叔丁基二甲基甲硅烷基（TBDMS）醚的相对构型，以及格拉纳酮（9-甲基- 9-氮杂双环[3.3.1]壬烷-3-one)，由核磁共振数据和观察到的非对映异构体的相互转化（外向，反内向，syn 和外向，syn 向内，反）确定。在硅胶存在下，外型转化为内型异构体。通过比较羟醛异构体的 NMR 数据，特别是相应的邻位偶联常数和位移，将通过托品酮和苯甲醛在水存在下的直接无溶剂反应合成得到的托品酮醛醇的新异构体的相对构型被确定为 exo,syn到侧链 CH 基团，
• 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.