(1R,4S)-2-(p-Methoxybenzyl)-2-azabicylo<2.2.1>heptane-3,6-dione | 168773-57-7

• 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: (1R,4S)-2-(p-Methoxybenzyl)-2-azabicylo<2.2.1>heptane-3,6-dione
• 英文别名: (1R,4S)-6-(4-methoxybenzyl)-6-aza-bicyclo[2.2.1]heptane-2,5-dione；(1R,4S)-2-[(4-methoxyphenyl)methyl]-2-azabicyclo[2.2.1]heptane-3,6-dione
• CAS: 168773-57-7
• 化学式: C₁₄H₁₅NO₃
• 分子量: 245.278
• InChiKey: XDNGSLMBVIPJCH-CMPLNLGQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 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：

  (1R,4S)-2-(p-Methoxybenzyl)-2-azabicylo<2.2.1>heptane-3,6-dione 在 palladium diacetate 、 三苯基膦 甲酸 、 三正丁胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 (1R,4S)-2-(4-methoxybenzyl)-2-azabicyclo[2.2.1]hept-5-en-3-one
  参考文献：
  名称：

  Chirospecific Syntheses of Precursors of Cyclopentane and Cyclopentene Carbocyclic Nucleosides by [3 + 3]-Coupling and Transannular Alkylation

  摘要：

  A new method is reported for the preparation of enantiomerically pure (1R,2S,4S)-1-amino-2-hydroxy-4-(hydroxymethyl)cyclopentane, (1R,2R,4S)-1-amino-2-fluoro-4-(hydroxymethyl)cyclopentane, and (1R,4S)-1-amino-4-(hydroxymethyl)-2-cyclopentene, advanced precursors to carbocyclic nucleosides. The method involves initial conversion of D-serine into an aldehyde with 9-phenylfluorenyl protection at nitrogen and O-benzyl protection at oxygen. A [3 + 3]-coupling of this aldehyde with a titanium homoenolate derived from tert-butyl 3-iodopropionate gave the corresponding anti-lactone in high yield. Regioselective hydrogenolysis of the amine protecting group, accompanied by intramolecular O- to N-cyclization formed a lactam. After suitable nitrogen protection and functional group manipulation, transannular alkylation afforded the corresponding 2-benzyl- or 2-(p-methoxybenzyl)-6-hydroxy-2-azabicycclo[2.2.1]-3-heptanone. Functional group modification of the 2-benzyl analogue gave the resulting 6(S)-hydroxy and 6(R)-fluoro N-BOC imides; alternatively, the 2-(p-methoxybenzyl) analogue was converted to an N-BOC imide containing an olefinic Linkage at C-5 and C-6 of the bicycle. Subjecting each of the N-BOC imides to a reduction-deprotection sequence then afforded the desired carbocyclic analogues. The [3 + 3]-coupling method also allowed improved and expedient access to an advanced tribenzylated lactam previously used in the racemic syntheses of the hydroxylated alkaloids D-mannonolactam, deoxymannojirimycin, and prosopinone, providing a formal asymmetric synthesis of these alkaloids.

  DOI：

  10.1021/jo00119a044
• 作为产物：
  描述：

  (1R,4S,6S)-6-Hydroxy-2-(p-methoxybenzyl)-2-azabicyclo<2.2.1>-3-heptanone 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 以97%的产率得到(1R,4S)-2-(p-Methoxybenzyl)-2-azabicylo<2.2.1>heptane-3,6-dione
  参考文献：
  名称：

  钯纳米簇对C 3或C 3 v对称的顺式-Tris（norborneno）苯催化对映体纯的碘降冰片烯的立体选择性环三聚

  摘要：

  通过Pd对映体纯的碘基降冰片烯的环三聚反应，合成了具有各种官能团的C 3或C 3 v对称的对映体纯的顺式三（降冰片烯）苯。Pd催化合成的三（norborneno）苯的环三聚反应的普遍性已得到充分证明。

  DOI：

  10.1021/jo100710h

文献信息

• Chirospecific Syntheses of Precursors of Cyclopentane and Cyclopentene Carbocyclic Nucleosides by [3 + 3]-Coupling and Transannular Alkylation
  作者：Jeffrey A. Campbell、Won Koo Lee、Henry Rapoport

  DOI：10.1021/jo00119a044

  日期：1995.7

  A new method is reported for the preparation of enantiomerically pure (1R,2S,4S)-1-amino-2-hydroxy-4-(hydroxymethyl)cyclopentane, (1R,2R,4S)-1-amino-2-fluoro-4-(hydroxymethyl)cyclopentane, and (1R,4S)-1-amino-4-(hydroxymethyl)-2-cyclopentene, advanced precursors to carbocyclic nucleosides. The method involves initial conversion of D-serine into an aldehyde with 9-phenylfluorenyl protection at nitrogen and O-benzyl protection at oxygen. A [3 + 3]-coupling of this aldehyde with a titanium homoenolate derived from tert-butyl 3-iodopropionate gave the corresponding anti-lactone in high yield. Regioselective hydrogenolysis of the amine protecting group, accompanied by intramolecular O- to N-cyclization formed a lactam. After suitable nitrogen protection and functional group manipulation, transannular alkylation afforded the corresponding 2-benzyl- or 2-(p-methoxybenzyl)-6-hydroxy-2-azabicycclo[2.2.1]-3-heptanone. Functional group modification of the 2-benzyl analogue gave the resulting 6(S)-hydroxy and 6(R)-fluoro N-BOC imides; alternatively, the 2-(p-methoxybenzyl) analogue was converted to an N-BOC imide containing an olefinic Linkage at C-5 and C-6 of the bicycle. Subjecting each of the N-BOC imides to a reduction-deprotection sequence then afforded the desired carbocyclic analogues. The [3 + 3]-coupling method also allowed improved and expedient access to an advanced tribenzylated lactam previously used in the racemic syntheses of the hydroxylated alkaloids D-mannonolactam, deoxymannojirimycin, and prosopinone, providing a formal asymmetric synthesis of these alkaloids.
• Stereoselective Cyclotrimerization of Enantiopure Iodonorbornenes Catalyzed by Pd Nanoclusters for <i>C</i>₃ or <i>C</i>_3<i>v</i> Symmetric <i>syn</i>-Tris(norborneno)benzenes
  作者：Shuhei Higashibayashi、A. F. G. Masud Reza、Hidehiro Sakurai

  DOI：10.1021/jo100710h

  日期：2010.7.2

  C3 or C3v symmetric enantiopure syn-tris(norborneno)benzenes with various functional groups were synthesized through Pd-catalyzed cyclotrimerization of enantiopure iodonorbornenes. The generality of Pd-catalyzed cyclotrimerization for syn-tris(norborneno)benzenes were well-demonstrated.

  通过Pd对映体纯的碘基降冰片烯的环三聚反应，合成了具有各种官能团的C 3或C 3 v对称的对映体纯的顺式三（降冰片烯）苯。Pd催化合成的三（norborneno）苯的环三聚反应的普遍性已得到充分证明。