(2S)-2-Hydroxy-2-(4-isopropylphenyl)acetic acid methyl ester

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (2S)-2-Hydroxy-2-(4-isopropylphenyl)acetic acid methyl ester
• 英文别名: methyl (2S)-2-hydroxy-2-(4-propan-2-ylphenyl)acetate
• 化学式: C₁₂H₁₆O₃
• 分子量: 208.257
• InChiKey: HDNMOOPTGUTCBA-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4'-异丙基苯乙酮 在 吡啶 、 selenium(IV) oxide 、 C₄₈H₅₀N₂O₂P₂Ru*2C₁₈H₁₅P*4Cl^(1-)*2Ru⁽²⁺⁾ 、 氢气 、 sodium acetate 、 potassium carbonate 、 三苯基膦 作用下， 以 甲醇 、 丙酮 为溶剂， 110.0 ℃ 、4.0 MPa 条件下， 反应 36.0h， 生成 (2S)-2-Hydroxy-2-(4-isopropylphenyl)acetic acid methyl ester
  参考文献：
  名称：

  RuPHOX-Ru催化不对称加氢合成手性α-芳基α-羟基羧酸

  摘要：

  已成功开发了钌烯基膦基-恶唑啉-钌络合物（RuPHOX-Ru）催化的α-芳基酮酸不对称氢化反应，可提供高收率和ee高达97％的相应手性α-芳基α-羟基羧酸。该反应可以在相对较低的催化剂负载量（至多5000 S / C）下以克为单位进行，所得产物可以转化为几种手性结构单元，生物活性化合物和手性药物。

  DOI：

  10.1002/adsc.201700846

文献信息

• Chemoenzymatic Preparation of Enantiomerically Enriched (<i>R</i>)‐(–)‐Mandelic Acid Derivatives: Application in the Synthesis of the Active Agent Pemoline
  作者：Marcin Poterała、Maciej Dranka、Paweł Borowiecki

  DOI：10.1002/ejoc.201700161

  日期：2017.4.26

  resolution of several racemic derivatives of mandelic acid methyl ester catalyzed by lipases from Pseudomonas fluorescens (Amano AK) or Burkholderia cepacia (Amano PS-C II and Amano PS-IM) has been achieved. A gram-scale lipase-mediated kinetic resolution approach has been developed that allows the facile synthesis of the corresponding methyl (R)-(–)-mandelates with excellent enantiomeric excesses (up to

  已经实现了由荧光假单胞菌 (Amano AK) 或洋葱伯克霍尔德菌 (Amano PS-C II 和 Amano PS-IM) 的脂肪酶催化的扁桃酸甲酯的几种外消旋衍生物的对映选择性拆分。已经开发出一种克级脂肪酶介导的动力学拆分方法，可以轻松合成相应的甲基 (R)-(–)-扁桃酸，具有出色的对映体过量（高达 > 99 % ee）和反应对映选择性（E 值高达到 >200）。用于治疗注意力缺陷多动障碍 (ADHD) 和发作性睡病的多巴胺能药物 pemoline 是通过在碱性条件下将制备的 (R)-(-)-扁桃酸甲酯与盐酸胍缩合，以 98% 的 ee 直接合成的。使适应。光学纯形式的所需 (R)-(+)-pemoline (> 从乙醇中重结晶两次后获得 99% ee)。然而，手性 HPLC 证实旋光性匹莫林在甲醇溶液中发生外消旋化。
• Asymmetric Nucleophilic Acylation of Aldehydes via 1,1-Heterodisubstituted Alkenes
  作者：Holger Monenschein、Gerald Dräger、Alexander Jung、Andreas Kirschning

  DOI：10.1002/(sici)1521-3765(19990802)5:8<2270::aid-chem2270>3.0.co;2-l

  日期：1999.8.2

  Aldehydes are asymmetrically acylated by a two step sequence that is initiated by a homologation step to 1,1-heterodisubstituted alkenes followed by asymmetric dihydroxylation. Thus, ketene O,S-acetals are efficiently prepared from aldehydes by a Peterson olefination with lithiated methoxy-phenylthiotrimethylsilyl methane 14 as the C-1 source. Although they are dihydroxylated with the Sharpless catalyst with moderate to good enantioselectivity (62-80% ee), the process is not efficient owing to the low chemical yields of the desired alpha-hydroxy methyl esters (7-37%). Use of the corresponding sulfoxide 24 or sulfon 25 led to an improved chemical yield of alpha-hydroxy methyl ester 19, but the stereoselectivity was diminished. In contrast, intermediate ketene O,O-acetals are prepared by a Horner-Wittig reaction with phosphine oxide 31 and are dihydroxylated both with good chemical and stereochemical yield. The concept is applicable to aromatic, aliphatic, and chiral aldehydes. For example, this short sequence allows exclusive and independent preparation of both diastereomeric heptoses 69a and 69b.
• The Synthesis of Chiral α-Aryl α-Hydroxy Carboxylic Acids via RuPHOX-Ru Catalyzed Asymmetric Hydrogenation
  作者：Huan Guo、Jing Li、Delong Liu、Wanbin Zhang

  DOI：10.1002/adsc.201700846

  日期：2017.10.25

  A ruthenocenyl phosphino‐oxazoline‐ruthenium complex (RuPHOX−Ru) catalyzed asymmetric hydrogenation of α‐aryl keto acids has been successfully developed, affording the corresponding chiral α‐aryl α‐hydroxy carboxylic acids in high yields and with up to 97% ee. The reaction could be performed on a gram scale with a relatively low catalyst loading (up to 5000 S/C) and the resulting products can be transformed

  已成功开发了钌烯基膦基-恶唑啉-钌络合物（RuPHOX-Ru）催化的α-芳基酮酸不对称氢化反应，可提供高收率和ee高达97％的相应手性α-芳基α-羟基羧酸。该反应可以在相对较低的催化剂负载量（至多5000 S / C）下以克为单位进行，所得产物可以转化为几种手性结构单元，生物活性化合物和手性药物。