2-benzyl-2-azabicyclo<2.2.1>hept-5-en-3-one | 168960-16-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-benzyl-2-azabicyclo<2.2.1>hept-5-en-3-one
• 英文别名: (1R,4S)-2-Benzyl-2-azabicyclo<2.2.1>-5-hepten-3-one；(1R,4S)-2-benzyl-2-azabicyclo[2.2.1]hept-5-en-3-one
• CAS: 168960-16-5
• 化学式: C₁₃H₁₃NO
• 分子量: 199.252
• InChiKey: XEFJEWOXUFCIDO-NEPJUHHUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-benzyl-2-azabicyclo<2.2.1>hept-5-en-3-one 在 palladium on activated charcoal 氢气 作用下， 生成 (1R,4S)-2-苄基-2-氮杂双环[2.2.1]庚烷-3-酮
  参考文献：
  名称：

  Synthesis Of Monohydroxylated 2-Azabicyclo[2.2.1]heptan-3-ones.

  摘要：

  Oxymercuration/demercuration of 2-benzyl-2-azabicyclo[2.2.1]hept-5-en-3-one (1) and biohydroxylation of the corresponding saturated lactam (-)-(8) are compared as methods for the preparation of monohydroxylated 2-azabicyclo[2.2.1]heptan-3-ones. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00217-5
• 作为产物：
  描述：

  (5S,6R)-1-Benzyl-5-<(tert-butyldimethylsilyl)oxy>-6-(hydroxymethyl)-2-piperidinone 在 咪唑 、 四溴化碳 、 四丁基氟化铵 、 碘 、 双(三甲基硅烷基)氨基钾 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 、 xylene 为溶剂， 反应 34.41h， 生成 2-benzyl-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

文献信息

• Conformationally Restricted Carbocyclic γ-Amino Acids: Synthesis of Diastereomeric 3-Amino-5-arylcyclopentane 1-Carboxylic Acids
  作者：Stephen Hanessian、Adrien Dumas、Da Li、Steven Bonert、Prashansing Aubeelucksing、Arnaud-Pierre Schaffner

  DOI：10.1055/s-0042-1751484

  日期：2023.11

  previously unreported diastereoisomeric 3-amino-5-arylcyclopentane 1-carboxylic acids via the corresponding 3-hydroxy and 3-azido precursors. The availability of these conformationally restricted cyclic amino acids may find utility in the context of CNS-active compounds related to GABA, or as peripheral units of bioactive pharmaceuticals. An expedient alternative 4-step synthesis of 3S-amino-5S-p-hy

  公开了带有 Evans 助剂的对苄氧基肉桂酸酯与 1-三甲基甲硅烷基-2-乙酰氧基甲基丙烯之间的 Trost Pd 催化的 [3+2] 环加成反应，在官能团操作后，产生了先前未报道的非对映异构体 3-氨基-5-芳基环戊烷1 -羧酸通过相应的3-羟基和3-叠氮基前体。这些构象限制性环状氨基酸的可用性可能会在与 GABA 相关的 CNS 活性化合物中发挥作用，或作为生物活性药物的外围单元。3S-氨基-5S-对羟基苯基-1S的便捷替代四步合成-环戊烷甲酸甲酯是从 (–)-Vince 内酰胺开始并利用区域选择性和非对映选择性 Pd 催化的加氢芳基化反应获得的。
• 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.
• Synthesis Of Monohydroxylated 2-Azabicyclo[2.2.1]heptan-3-ones.
  作者：Christopher F Palmer、Ben Webb、Susan Broad、Sharon Casson、Raymond McCague、Andrew J Willetts、Stanley M Roberts

  DOI：10.1016/s0960-894x(97)00217-5

  日期：1997.5

  Oxymercuration/demercuration of 2-benzyl-2-azabicyclo[2.2.1]hept-5-en-3-one (1) and biohydroxylation of the corresponding saturated lactam (-)-(8) are compared as methods for the preparation of monohydroxylated 2-azabicyclo[2.2.1]heptan-3-ones. (C) 1997 Elsevier Science Ltd.