2-chloro-3-isopropylimino-2-methyl-1,3-diphenylpropan-1-ol

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 2-chloro-3-isopropylimino-2-methyl-1,3-diphenylpropan-1-ol
• 英文别名: (1S,2S)-2-chloro-2-methyl-1,3-diphenyl-3-propan-2-yliminopropan-1-ol
• 化学式: C₁₉H₂₂ClNO
• 分子量: 315.843
• InChiKey: AEOVEFJLZITBKT-OALUTQOASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  32.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-chloro-3-isopropylimino-2-methyl-1,3-diphenylpropan-1-ol 在 吡啶 、 sodium cyanoborohydride 、 potassium carbonate 、 溶剂黄146 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 94.0h， 生成 3-chloro-1-isopropyl-3-methyl-2,4-diphenylazetidine
  参考文献：
  名称：

  Diastereoselective Aldol Reaction of Zincated 3-Chloro-3-methyl-1-azaallylic Anions as Key Step in the Synthesis of 1,2,3,4-Tetrasubstituted 3-Chloroazetidines

  摘要：

  Zincated 3-chloro-3-methyl-1-azaallylic anions undergo a stereoselective aldol addition across aromatic aldehydes and subsequent mesylation to produce syn alpha-chloro-beta-mesyloxyketimines, which were isolated in 80-84% yield and high diastereomeric excess (dr > 97/3) after purification via flash chromatography. The syn alpha-chloro-beta-mesyloxyketimines were further stereoselectively reduced to give stereochemically defined 3-aminopropyl mesylates, which were cyclized to 1,2,3,4-tetrasubstituted 3-chloroazetidines containing three contiguous stereogenic centers. DFT calculations on the key aldol addition revealed the presence of a highly ordered bimetallic six-membered twist-boat-like transition state structure with a tetra-coordinated metal cyclic structure. DFT calculations revealed that chelation of both zinc and lithium cations in the transition state structure leads to the experimentally observed high syn diastereoselectivity of aldol reactions.

  DOI：

  10.1021/jo300203t
• 作为产物：
  描述：

  N-(2-chloro-1-phenylpropylidene)isopropylamine 、 苯甲醛 在 正丁基锂 、 二异丙胺 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.5h， 以39%的产率得到2-chloro-3-isopropylimino-2-methyl-1,3-diphenylpropan-1-ol
  参考文献：
  名称：

  Diastereoselective Aldol Reaction of Zincated 3-Chloro-3-methyl-1-azaallylic Anions as Key Step in the Synthesis of 1,2,3,4-Tetrasubstituted 3-Chloroazetidines

  摘要：

  Zincated 3-chloro-3-methyl-1-azaallylic anions undergo a stereoselective aldol addition across aromatic aldehydes and subsequent mesylation to produce syn alpha-chloro-beta-mesyloxyketimines, which were isolated in 80-84% yield and high diastereomeric excess (dr > 97/3) after purification via flash chromatography. The syn alpha-chloro-beta-mesyloxyketimines were further stereoselectively reduced to give stereochemically defined 3-aminopropyl mesylates, which were cyclized to 1,2,3,4-tetrasubstituted 3-chloroazetidines containing three contiguous stereogenic centers. DFT calculations on the key aldol addition revealed the presence of a highly ordered bimetallic six-membered twist-boat-like transition state structure with a tetra-coordinated metal cyclic structure. DFT calculations revealed that chelation of both zinc and lithium cations in the transition state structure leads to the experimentally observed high syn diastereoselectivity of aldol reactions.

  DOI：

  10.1021/jo300203t

文献信息

• Diastereoselective Aldol Reaction of Zincated 3-Chloro-3-methyl-1-azaallylic Anions as Key Step in the Synthesis of 1,2,3,4-Tetrasubstituted 3-Chloroazetidines
  作者：Sven Mangelinckx、Bart De Sterck、Filip Colpaert、Saron Catak、Jan Jacobs、Stijn Rooryck、Michel Waroquier、Veronique Van Speybroeck、Norbert De Kimpe

  DOI：10.1021/jo300203t

  日期：2012.4.6

  Zincated 3-chloro-3-methyl-1-azaallylic anions undergo a stereoselective aldol addition across aromatic aldehydes and subsequent mesylation to produce syn alpha-chloro-beta-mesyloxyketimines, which were isolated in 80-84% yield and high diastereomeric excess (dr > 97/3) after purification via flash chromatography. The syn alpha-chloro-beta-mesyloxyketimines were further stereoselectively reduced to give stereochemically defined 3-aminopropyl mesylates, which were cyclized to 1,2,3,4-tetrasubstituted 3-chloroazetidines containing three contiguous stereogenic centers. DFT calculations on the key aldol addition revealed the presence of a highly ordered bimetallic six-membered twist-boat-like transition state structure with a tetra-coordinated metal cyclic structure. DFT calculations revealed that chelation of both zinc and lithium cations in the transition state structure leads to the experimentally observed high syn diastereoselectivity of aldol reactions.