exo-rac-(1S,3S,4S)-3-(4-fluorophenyl)-2-(4-methoxyphenyl)-2-azabicyclo[2.2.2]octan-5-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: exo-rac-(1S,3S,4S)-3-(4-fluorophenyl)-2-(4-methoxyphenyl)-2-azabicyclo[2.2.2]octan-5-one
• 英文别名: rel-(1S,3S,4S)-3-(4-fluorophenyl)-2-(4-methoxyphenyl)-2-azabicyclo-[2.2.2]octan-5-one；3-exo-(4-fluorophenyl)-2-(4-methoxyphenyl)-2-azabicyclo[2.2.2]octan-5-one；(1S,3S,4S)-3-(4-fluorophenyl)-2-(4-methoxyphenyl)-2-azabicyclo[2.2.2]octan-5-one
• 化学式: C₂₀H₂₀FNO₂
• 分子量: 325.383
• InChiKey: SRFRGZUCPVISGL-ILZDJORESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-环己烯-1-酮 、 4-甲氧基-N-(4-氟亚苄基)苯胺 在 zirconioum phosphate monohydrate 、 sodium dodecyl-sulfate 作用下， 以 水 为溶剂， 反应 24.0h， 以47%的产率得到endo-rac-(1S,3R,4S)-3-(4-fluorophenyl)-2-(4-methoxyphenyl)-2-azabicyclo[2.2.2]octan-5-one
  参考文献：
  名称：

  层状α-磷酸氢锆和十二烷基硫酸钠催化水中的直接氮杂-狄尔斯-阿尔德反应

  摘要：

  2-cyclohexen-1-one (1) 和苯二亚胺 2 在水中的直接 aza-Diels-Alder 反应是首次报道。该反应在 30 °C 下发生，由层状 α-磷酸氢锆 (α-ZrP) 催化，需要存在十二烷基硫酸钠 (SDS)。与使用有机溶剂相比，反应收率极好，反应速度更快，外非对映选择性更高。还研究了反应的一锅、三组分版本以及催化剂和含水母液（水、α-ZrP 和 SDS）的再循环。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

  DOI：

  10.1002/ejoc.200801132

文献信息

• An efficient synthesis of 2,3-diaryl-2-azabicyclo[2.2.2]octan-5-ones and their acetylcholinesterase inhibitory activity
  作者：Li Huang、Jun-Pei Chen、Can Jin、Wei-Ke Su

  DOI：10.1016/j.cclet.2013.01.045

  日期：2013.4

  Abstract A series of substituted 2,3-diaryl-2-azabicyclo[2.2.2]octan-5-ones have been prepared by an efficient three-component aza-Diels–Alder cycloaddition reaction in water catalyzed by layered α -zirconium hydrogen phosphate ( α -ZrP) and sodium calix[4]arene sulfonates bearing pendant short aliphatic chains. The 18 synthesized compounds were assayed for acetylcholinesterase inhibition using mouse

  摘要通过α-磷酸氢锆层状催化剂在水中高效地进行三组分氮杂-狄尔斯-阿尔德环加成反应，制备了一系列取代的2,3-二芳基-2-氮杂双环[2.2.2]辛烷-5-酮（α-ZrP）和杯芳烃磺酸钠[4]亚芳基磺酸盐带有短的脂肪族侧链。使用小鼠乙酰胆碱酯酶测定了18种合成化合物对乙酰胆碱酯酶的抑制作用。
• <i>N</i>-Fluorobenzenesulfonimide as Catalyst for the Three-Component Synthesis of Isoquinuclidines
  作者：D. Wu、Y-H. He、X. Deng、Z. Guan

  DOI：10.1002/jhet.1544

  日期：2013.3

  N‐Fluorobenzenesulfonimide was used for the first time as a catalyst to carry out the three‐component synthesis of isoquinuclidines with the use of various cyclohexenone (1), benzaldehydes (2), and anilines (3). The yields up to 80% and the endo/exo stereoselectivity ratios up to 19:81 were achieved.

  N-氟苯磺酰亚胺首次用作催化剂，使用各种环己烯酮（1），苯甲醛（2）和苯胺（3）进行异喹核苷的三组分合成。收率高达80％，内/外立体选择性高达19:81。
• Enzyme-Catalyzed Direct Three-Component Aza-Diels–Alder Reaction Using Hen Egg White Lysozyme
  作者：Yan-Hong He、Wen Hu、Zhi Guan

  DOI：10.1021/jo2016696

  日期：2012.1.6

  The direct three-component aza-Diels-Alder reaction of aromatic aldehyde, aromatic amine, and 2-cyclohexen-1-one was catalyzed by hen egg white lysozyme for the first time. Under the optimized conditions investigated in this paper, the enzyme-catalyzed aza-Diels-Alder reaction gave yields up to 98% and stereoselectivity of endo/exo ratios up to 90:10.
• Enantioselective Direct Aza Hetero-Diels−Alder Reaction Catalyzed by Chiral Brønsted Acids
  作者：Hua Liu、Lin-Feng Cun、Ai-Qiao Mi、Yao-Zhong Jiang、Liu-Zhu Gong

  DOI：10.1021/ol062499t

  日期：2006.12.1

  The first chiral Bronsted acid-catalyzed asymmetric direct aza hetero-Diels-Alder reaction has been described. The phosphoric acids, prepared from binol and H-8-binol derivatives, have shown catalytic ability for the reaction of cyclohexenone with N-PMP-benzaldimine. A chiral phosphoric acid, derived from 3,3-di(4-chloropheneyl)-H-8-binol, exhibited superior enantioselectivity, affording fairly good yields and enantioselectivities for the reaction of a range of aromatic aldimines with cyclohexenone.
• Direct Aza-Diels-Alder Reaction in Water Catalyzed by Layered α-Zirconium Hydrogen Phosphate and Sodium Dodecyl Sulfate
  作者：Umberto Costantino、Francesco Fringuelli、Mara Orrù、Morena Nocchetti、Oriana Piermatti、Ferdinando Pizzo

  DOI：10.1002/ejoc.200801132

  日期：2009.3

  The direct aza-Diels–Alder reaction between 2-cyclohexen-1-one (1) and benzaldimines 2 in water is reported for the first time. The reaction occurs at 30 °C, is catalyzed by layered α-zirconium hydrogen phosphate (α-ZrP) and requires the presence of sodium dodecyl sulfate (SDS). The reaction yield is excellent, the reaction is faster and the exo diastereoselectivity is higher than when organic solvent

  2-cyclohexen-1-one (1) 和苯二亚胺 2 在水中的直接 aza-Diels-Alder 反应是首次报道。该反应在 30 °C 下发生，由层状 α-磷酸氢锆 (α-ZrP) 催化，需要存在十二烷基硫酸钠 (SDS)。与使用有机溶剂相比，反应收率极好，反应速度更快，外非对映选择性更高。还研究了反应的一锅、三组分版本以及催化剂和含水母液（水、α-ZrP 和 SDS）的再循环。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)