(2S,3S,4S)-3,4-bis(methoxymethoxy)-2-[(4-methoxyphenyl)methyl]pyrrolidine | 159180-58-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (2S,3S,4S)-3,4-bis(methoxymethoxy)-2-[(4-methoxyphenyl)methyl]pyrrolidine
• CAS: 159180-58-2
• 化学式: C₁₆H₂₅NO₅
• 分子量: 311.378
• InChiKey: YZGFKXGNHHJDFL-JYJNAYRXSA-N

物化性质

• 沸点：
  395.4±42.0 °C(predicted)
• 密度：
  1.13±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  58.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,3S,4S)-3,4-bis(methoxymethoxy)-2-[(4-methoxyphenyl)methyl]pyrrolidine 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 22.0h， 以45%的产率得到(2S,3S,4S)-2-(4-Methoxy-benzyl)-pyrrolidine-3,4-diol
  参考文献：
  名称：

  Exploratory Synthetic Studies of the α-Methoxylation of Amides via Cuprous Ion-Promoted Decomposition of o-Diazobenzamides

  摘要：

  A convenient nonelectrochemical amide oxidation method has been developed. The process involves a cuprous ion-promoted decomposition of o-diazobenzamides like 4, generated in situ from the corresponding o-aminobenzamides, to give N-acyliminium ion intermediate 9 via a 1,5-H-atom transfer, followed by metal-catalyzed oxidation of the resulting alpha-amidyl radical. The transformation produces alpha-methoxybenzamides 15 in good yields. An attempt was made to apply this oxidation method to a total synthesis of the alkaloid (-)-anisomycin (16). Scalemic o-aminobenzamide pyrrolidine derivatives 18a/18b underwent oxidation to give a-methoxylated amide substrates 19a/ 19b, respectively, in good yields. However, alkylation of the N-acyliminium intermediate 20 with (p-methoxybenzyl)magnesium chloride gave the undesired anti-compounds 22a/22b as the major products. The amide oxidation exhibits good regioselectivity with many unsymmetrical 2-substituted piperidine and pyrrolidine systems. In general, it appears that the larger the C-2 substituent, the greater the methylene/methine H-atom abstraction ratio. A mechanistic rationale for this selectivity is suggested based upon amide rotamer populations. An extension of this methodology can be used to conduct two sequential amide oxidations using readily prepared 2-amino-6-nitrobenzamides such as 68 and 69.

  DOI：

  10.1021/jo961529a
• 作为产物：
  描述：

  (2-aminophenyl)-[(3S,4S)-3,4-bis(methoxymethoxy)pyrrolidin-1-yl]methanone 在 盐酸 、 copper(l) chloride 、 sodium nitrite 作用下， 以 乙醚 、 水 为溶剂， 反应 2.0h， 生成 (2S,3S,4S)-3,4-bis(methoxymethoxy)-2-[(4-methoxyphenyl)methyl]pyrrolidine
  参考文献：
  名称：

  一种方便的酰胺氧化合成方法

  摘要：

  在催化量的CuCl存在下，将邻氨基苯甲酰胺在甲醇中重氮化，可得到高产率的α-甲氧基苯甲酰胺。

  DOI：

  10.1016/s0040-4039(00)78191-3

文献信息

• A convenient synthetic method for amide oxidation
  作者：Gyoonhee Han、Matthias C McIntosh、Steven M Weinreb

  DOI：10.1016/s0040-4039(00)78191-3

  日期：1994.8

  Diazotization of o-aminobenzamides in methanol in the presence of a catalytic amount of CuCl affords α-methoxybenzamides in good yields.

  在催化量的CuCl存在下，将邻氨基苯甲酰胺在甲醇中重氮化，可得到高产率的α-甲氧基苯甲酰胺。
• Exploratory Synthetic Studies of the α-Methoxylation of Amides <i>via</i> Cuprous Ion-Promoted Decomposition of <i>o</i>-Diazobenzamides
  作者：Gyoonhee Han、Matthew G. LaPorte、Mathias C. McIntosh、Steven M. Weinreb、Masood Parvez

  DOI：10.1021/jo961529a

  日期：1996.1.1

  A convenient nonelectrochemical amide oxidation method has been developed. The process involves a cuprous ion-promoted decomposition of o-diazobenzamides like 4, generated in situ from the corresponding o-aminobenzamides, to give N-acyliminium ion intermediate 9 via a 1,5-H-atom transfer, followed by metal-catalyzed oxidation of the resulting alpha-amidyl radical. The transformation produces alpha-methoxybenzamides 15 in good yields. An attempt was made to apply this oxidation method to a total synthesis of the alkaloid (-)-anisomycin (16). Scalemic o-aminobenzamide pyrrolidine derivatives 18a/18b underwent oxidation to give a-methoxylated amide substrates 19a/ 19b, respectively, in good yields. However, alkylation of the N-acyliminium intermediate 20 with (p-methoxybenzyl)magnesium chloride gave the undesired anti-compounds 22a/22b as the major products. The amide oxidation exhibits good regioselectivity with many unsymmetrical 2-substituted piperidine and pyrrolidine systems. In general, it appears that the larger the C-2 substituent, the greater the methylene/methine H-atom abstraction ratio. A mechanistic rationale for this selectivity is suggested based upon amide rotamer populations. An extension of this methodology can be used to conduct two sequential amide oxidations using readily prepared 2-amino-6-nitrobenzamides such as 68 and 69.