phenyl (1R,4R,7R)-7-(2-benzyl-3,3-dimethyl-5-oxopyrazolidine-1-carbonyl)-2-azabicyclo[2.2.2]oct-5-ene-2-carboxylate | 864379-95-3

• 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: phenyl (1R,4R,7R)-7-(2-benzyl-3,3-dimethyl-5-oxopyrazolidine-1-carbonyl)-2-azabicyclo[2.2.2]oct-5-ene-2-carboxylate
• CAS: 864379-95-3
• 化学式: C₂₇H₂₉N₃O₄
• 分子量: 459.545
• InChiKey: HIVIBKJUBFOYLJ-MDNUFGMLSA-N

物化性质

• 熔点：
  165-168 °C
• 沸点：
  596.4±60.0 °C(predicted)
• 密度：
  1.270±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  70.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  phenyl (1R,4R,7R)-7-(2-benzyl-3,3-dimethyl-5-oxopyrazolidine-1-carbonyl)-2-azabicyclo[2.2.2]oct-5-ene-2-carboxylate 、 lithium methanolate 在 正丁基锂 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 6-O-methyl 2-O-phenyl (1R,4R,6R)-2-azabicyclo[2.2.2]oct-7-ene-2,6-dicarboxylate
  参考文献：
  名称：

  A novel chiral oxazolidine organocatalyst for the synthesis of an oseltamivir intermediate using a highly enantioselective Diels–Alder reaction of 1,2-dihydropyridine

  摘要：

  使用一种新型手性噁唑啉有机催化剂，通过1,2-二氢吡啶与丙烯醛的对映选择性Diels-Alder反应，合成了作为奥司他韦高效合成中间体的对映选择性异喹啉化合物，具有相当好的化学产率和极高的对映选择性（90%，高达>99% 对映体过量）。

  DOI：

  10.1039/c0cc00110d
• 作为产物：
  描述：

  3-吡唑烷酮,5,5-二甲基-1-(苯基甲基)- 在 copper(II) bis(trifluoromethanesulfonate) 、 lithium chloride 、 S-4,5-二氢-2-(2-((S)-4,5-二氢-4-异丙基噁唑-2-基)丙-2-基)-4-异丙基噁唑 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 生成 phenyl (1R,4R,7R)-7-(2-benzyl-3,3-dimethyl-5-oxopyrazolidine-1-carbonyl)-2-azabicyclo[2.2.2]oct-5-ene-2-carboxylate 、 phenyl (1S,4S,7S)-7-(2-benzyl-3,3-dimethyl-5-oxopyrazolidine-1-carbonyl)-2-azabicyclo[2.2.2]oct-5-ene-2-carboxylate
  参考文献：
  名称：

  Highly Enantioselective Synthesis of Isoquinuclidine by Diels-Alder Reaction of 1,2-Dihydropyridine Utilizing Chiral Bisoxazoline-Cu(II) Complex

  摘要：

  The enantioselective Diels-Alder (D-A) reaction between N-phenoxycarbonyl- or N-benzyloxycarbonyl-1,2-dihydropyridine (1a or 1b) and N(2)-acryloyl-N(1)-(1-naphthylmethyl)-5,5-dimethylpyrazolidin-3-one (2b) using (S,S)-bisoxazoline-Cu(II) catalyst (A, B, C or D) has been investigated. Utilizing (S,S)-t-Bu-bisoxazoline-Cu(II) catalyst C, the D-A reaction of la and 2 afforded the endo-(7S)-isoquinuclidines (3, 4 or 5) in good chemical yields with high enantioselectivity (up to 99% e.e.).

  DOI：

  10.3987/com-12-s(n)2

文献信息

• The Role of Achiral Pyrazolidinone Templates in Enantioselective Diels−Alder Reactions:  Scope, Limitations, and Conformational Insights
  作者：Mukund P. Sibi、Levi M. Stanley、Xiaoping Nie、Lakshmanan Venkatraman、Mei Liu、Craig P. Jasperse

  DOI：10.1021/ja066425o

  日期：2007.1.1

  were also observed in reactions of 7d with chiral Lewis acids derived from relatively small chiral ligands, suggesting the pyrazolidinone templates are capable of relaying stereochemical information from the ligand to the reaction center. Lewis acids capable of adapting square planar geometries, such as Cu(OTf)2, Cu(ClO4)2, and Pd(ClO4)2, were found to be particularly effective at providing high selectivities

  我们评估了非手性吡唑烷酮模板与手性路易斯酸在室温、对映选择性 Diels-Alder 环加成反应中的作用。检查了fluxional N(1) 取代基的作用，庞大的1-萘甲基组提供高达99%ee 的对映选择性，而具有较小fluxional 组的模板提供较低的选择性。在 7d 与衍生自相对较小手性配体的手性路易斯酸的反应中也观察到高选择性，表明吡唑烷酮模板能够将立体化学信息从配体传递到反应中心。发现能够适应方形平面几何形状的路易斯酸，例如 Cu(OTf)2、Cu(ClO4)2 和 Pd(ClO4)2，在提供高选择性方面特别有效。此外，已证明吡唑烷酮模板的 C-5 位取代对最佳选择性至关重要。附加有许多常见的亲二烯体和各种二烯的最佳吡唑烷酮的反应证明了这种非手性模板的实用性。此外，催化负载可以降低到 2.5 mol%，而选择性基本上没有损失。Pi-Pi 相互作用被评估为一种解释在室温下观察到的异常高选择性的手段。最后，采用非
• The highly enantioselective Diels–Alder reaction of 1,2-dihydropyridine using chiral cationic palladium–phosphinooxazolidine catalyst for the synthesis of chiral isoquinuclidines
  作者：Hiroto Nakano、Natsumi Tsugawa、Reiko Fujita

  DOI：10.1016/j.tetlet.2005.06.089

  日期：2005.8

  The enantio selective Diets-Alder reactions of 1-phenoxycarbonyl-1,2-dihydropyridine with 1-alkylated acryloyl-pyrazolidin-3-ones using chiral cationic palladium-phosphinooxazolidine (Pd-POZ) catalyst afforded chiral isoquinuclidines with excellent enantioselectivity (up to 97% ee). (c) 2005 Elsevier Ltd. All rights reserved.
• A novel chiral oxazolidine organocatalyst for the synthesis of an oseltamivir intermediate using a highly enantioselective Diels–Alder reaction of 1,2-dihydropyridine
  作者：Hiroto Nakano、Kenichi Osone、Mitsuhiro Takeshita、Eunsang Kwon、Chigusa Seki、Haruo Matsuyama、Nobuhiro Takano、Yoshihito Kohari

  DOI：10.1039/c0cc00110d

  日期：——

  Enantioselective Diels–Alder reactions of 1,2-dihydropyridines with acroleins using a novel chiral oxazolidine organocatalyst afforded chiral isoquinuclidines that is an efficient synthetic intermediate of oseltamivir, with fairly good chemical yield and excellent enantioselectivity (90%, up to >99% ee).

  使用一种新型手性噁唑啉有机催化剂，通过1,2-二氢吡啶与丙烯醛的对映选择性Diels-Alder反应，合成了作为奥司他韦高效合成中间体的对映选择性异喹啉化合物，具有相当好的化学产率和极高的对映选择性（90%，高达>99% 对映体过量）。
• Highly Enantioselective Synthesis of Isoquinuclidine by Diels-Alder Reaction of 1,2-Dihydropyridine Utilizing Chiral Bisoxazoline-Cu(II) Complex
  作者：Haruo Matsuyama、Chigusa Seki、Takashi Shimizu、Masafumi Hirama、Hiroto Nakano、Koji Uwai、Nobuhiro Takano、N. D. M. Romauli Hutabarat、Yoshihito Kohari、Eunsang Kwon

  DOI：10.3987/com-12-s(n)2

  日期：——

  The enantioselective Diels-Alder (D-A) reaction between N-phenoxycarbonyl- or N-benzyloxycarbonyl-1,2-dihydropyridine (1a or 1b) and N(2)-acryloyl-N(1)-(1-naphthylmethyl)-5,5-dimethylpyrazolidin-3-one (2b) using (S,S)-bisoxazoline-Cu(II) catalyst (A, B, C or D) has been investigated. Utilizing (S,S)-t-Bu-bisoxazoline-Cu(II) catalyst C, the D-A reaction of la and 2 afforded the endo-(7S)-isoquinuclidines (3, 4 or 5) in good chemical yields with high enantioselectivity (up to 99% e.e.).