(3R)-3-[(E)-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]iminomethyl]cyclopentan-1-one | 244234-79-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (3R)-3-[(E)-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]iminomethyl]cyclopentan-1-one
• CAS: 244234-79-5
• 化学式: C₁₂H₂₀N₂O₂
• 分子量: 224.303
• InChiKey: RKVHBMOFEBYWNF-LBSFFPRJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  41.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3R)-3-[(E)-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]iminomethyl]cyclopentan-1-one 在 对甲苯磺酸 作用下， 以 乙醚 、 甲苯 为溶剂， 反应 24.0h， 生成 methyl N-[(1R)-1-[(8R)-1,4-dioxaspiro[4.4]nonan-8-yl]ethyl]-N-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]carbamate
  参考文献：
  名称：

  Electrophilic and Nucleophilic Reactivities of the Azomethine Carbon of SAMP-Hydrazones:  Stereoselective Synthesis of γ-Amino Ketone Derivatives

  摘要：

  A novel methodology for the asymmetric synthesis of secondary N-Boc-protected gamma-amino ketones is described. After the highly diastereoselective nucleophilic 1,4-addition of formaldehyde SAMP-hydrazone 1 to prochiral conjugated enones 2, the carbonyl group of the resulting li-oxo aldehyde SAMP-hydrazones 4 was protected as ethylene ketals 5. The stereoselective (de 58-88%) addition of organometallic reagents to the CN double bond of the latter was then performed, and the unstable intermediate hydrazines obtained were either trapped as Moc-protected hydrazines 8 in good yields (65-87%) or reduced by Raney nickel-catalyzed hydrogenolysis of the N-N bond to afford the corresponding amines, which were isolated as their corresponding N-Boc derivatives 11. Noteworthy, the azomethine carbon of SAMP-hydrazones, not being essentially modified during the process, sequentially serves as a nucleophilic and an electrophilic center, acting as a nexus between the conjugated enone (electrophile) and the organometallic reagent (nucleophile) and helping in the creation of two adjacent stereogenic centers.

  DOI：

  10.1021/jo990503r
• 作为产物：
  描述：

  2-环戊烯酮 、 N-[2-(甲氧基甲基)-1-吡咯烷基]甲亚胺 在 四丁基氟化铵 、 (2,3-二甲基-2-丁烷基)(二甲基)硅烷基三氟甲烷磺酸酯 作用下， 生成 (3R)-3-[(E)-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]iminomethyl]cyclopentan-1-one 、
  参考文献：
  名称：

  Formaldehyde Dialkylhydrazones as Neutral Formyl Anion and Cyanide Equivalents:  Nucleophilic Addition to Conjugated Enones

  摘要：

  A versatile methodology for the nucleophilic formylation and cyanation of conjugated enones is reported. The procedure is based on the use of formaldehyde dimethylhydrazone, which, acting as a neutral formyl anion equivalent, adds to preformed trialkylsilyl-enone complexes. Both 4-(silyloxy)-3-enal hydrazones 3 or deprotected 4-oxo aldehyde monohydrazones 4 can be obtained as products depending on quenching conditions. In full analogy, an asymmetric version of the reaction using chiral formaldehyde SAMP-hydrazone as a neutral synthon of the chiral formyl anion has been developed, giving rise to the corresponding adducts 5 and 6 in good yields and with excellent diastereoselectivities (de 85-greater than or equal to 98%). Ozonolysis or HCl-mediated hydrolysis of adducts 4 and 6 readily affords racemic and optically enriched 4-oxo aldehydes 7, respectively. Additionally, high-yielding MMPP-oxidative cleavage of 4-oxo hydrazones 4 and 6 has been performed to obtain Li-oxo nitriles 8 in racemic and optically enriched forms, respectively. In this way, interesting chiral bifunctional building blocks, some of them bearing newly created stereogenic quaternary centers, have been efficiently synthesized.

  DOI：

  10.1021/jo970481d

文献信息

• Formaldehyde Dialkylhydrazones as Neutral Formyl Anion and Cyanide Equivalents:  Nucleophilic Addition to Conjugated Enones
  作者：Elena Díez、Rosario Fernández、Consolación Gasch、José M. Lassaletta、José M. Llera、Eloísa Martín-Zamora、Juan Vázquez

  DOI：10.1021/jo970481d

  日期：1997.7.1

  A versatile methodology for the nucleophilic formylation and cyanation of conjugated enones is reported. The procedure is based on the use of formaldehyde dimethylhydrazone, which, acting as a neutral formyl anion equivalent, adds to preformed trialkylsilyl-enone complexes. Both 4-(silyloxy)-3-enal hydrazones 3 or deprotected 4-oxo aldehyde monohydrazones 4 can be obtained as products depending on quenching conditions. In full analogy, an asymmetric version of the reaction using chiral formaldehyde SAMP-hydrazone as a neutral synthon of the chiral formyl anion has been developed, giving rise to the corresponding adducts 5 and 6 in good yields and with excellent diastereoselectivities (de 85-greater than or equal to 98%). Ozonolysis or HCl-mediated hydrolysis of adducts 4 and 6 readily affords racemic and optically enriched 4-oxo aldehydes 7, respectively. Additionally, high-yielding MMPP-oxidative cleavage of 4-oxo hydrazones 4 and 6 has been performed to obtain Li-oxo nitriles 8 in racemic and optically enriched forms, respectively. In this way, interesting chiral bifunctional building blocks, some of them bearing newly created stereogenic quaternary centers, have been efficiently synthesized.
• Electrophilic and Nucleophilic Reactivities of the Azomethine Carbon of SAMP-Hydrazones:  Stereoselective Synthesis of γ-Amino Ketone Derivatives
  作者：Dieter Enders、Elena Díez、Rosario Fernández、Eloísa Martín-Zamora、Jesús M. Muñoz、Rafael R. Pappalardo、José M. Lassaletta

  DOI：10.1021/jo990503r

  日期：1999.8.1

  A novel methodology for the asymmetric synthesis of secondary N-Boc-protected gamma-amino ketones is described. After the highly diastereoselective nucleophilic 1,4-addition of formaldehyde SAMP-hydrazone 1 to prochiral conjugated enones 2, the carbonyl group of the resulting li-oxo aldehyde SAMP-hydrazones 4 was protected as ethylene ketals 5. The stereoselective (de 58-88%) addition of organometallic reagents to the CN double bond of the latter was then performed, and the unstable intermediate hydrazines obtained were either trapped as Moc-protected hydrazines 8 in good yields (65-87%) or reduced by Raney nickel-catalyzed hydrogenolysis of the N-N bond to afford the corresponding amines, which were isolated as their corresponding N-Boc derivatives 11. Noteworthy, the azomethine carbon of SAMP-hydrazones, not being essentially modified during the process, sequentially serves as a nucleophilic and an electrophilic center, acting as a nexus between the conjugated enone (electrophile) and the organometallic reagent (nucleophile) and helping in the creation of two adjacent stereogenic centers.