ethyl 2-hydroxy-4-phenylbutanoate | 93921-85-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: ethyl 2-hydroxy-4-phenylbutanoate
• 英文别名: ethyl 2-hydroxy-4-phenylbutyrate；ethyl 2-R,S-hydroxy-4-phenylbutyrate；Ethyl 2-hydroxy-4-phenylbutyrate, (+/-)-
• CAS: 93921-85-8
• 化学式: C₁₂H₁₆O₃
• 分子量: 208.257
• InChiKey: ZJYKSSGYDPNKQS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  6
• 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

• 作为反应物：
  描述：

  ethyl 2-hydroxy-4-phenylbutanoate 以 四氢呋喃 、 甲醇 为溶剂， 以65%的产率得到4-phenylbutane-1,2-diol
  参考文献：
  名称：

  Palladium-Catalyzed meta-C–H Olefination of Arene-Tethered Diols Directed by Well-Designed Pyrimidine-Based Group

  摘要：

  The palladium-catalyzed meta-olefination of arene-tethered diols attached to a well-designed pyrimidine moiety is presented. Applications of the protocol are illustrated by the synthesis of various diol-based natural products, such as coumarins, phenylpropanoids, stilbenes, and chalcones. Advantages of this method are demonstrated through the easy removal of the template and a gram-scale olefination reaction. Finally, experimental verification, including H-1 NMR, ESI-MS and IR, and DFT studies are undertaken to elucidate the mechanistic complexity.

  DOI：

  10.1021/acs.orglett.9b00433
• 作为产物：
  描述：

  ethyl 2-diazo-4-phenylbutanoate 在 辛酸铑 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以83%的产率得到ethyl 2-hydroxy-4-phenylbutanoate
  参考文献：
  名称：

  可循环使用的聚合物支撑氧化剂在重氮化合物进料制备中促进的无卤烷基杂原子烷基化和环氧化

  摘要：

  高活性金属卡宾，是通过简单的酮类通过重氮化合物（包括重氮酰胺和膦酸酯）通过重氮化合物（使用可循环利用的试剂流入）生成的，是一种瞬态但通用的亲电子试剂，可用于杂原子烷基化反应和环氧化物的形成。该方法不产生有机废物，唯一的副产品是水，KI和氮气，并且没有分离中间体重氮化合物的伴随危险。

  DOI：

  10.1002/chem.201500118

文献信息

• N–O Tethered Carbenoid Cyclopropanation Facilitates the Synthesis of a Functionalized Cyclopropyl-Fused Pyrrolidine
  作者：Dimpy Kalia、Gökce Merey、Min Guo、Herman O. Sintim

  DOI：10.1021/jo400788a

  日期：2013.6.21

  We report a facile approach to a cyclopropyl-fused pyrrolidine, which contains four stereogenic centers, by employing the N–O tethered carbenoid methodology. The synthesis was facilitated by the development of a direct Mitsunobu reaction of alcohols with N-alkyl-N-hydroxyl amides to give diazo precursors, which upon intramolecular cyclopropanation yielded a library of N–O containing cyclopropyl-fused

  我们报告了一种采用N–O系链类胡萝卜素方法的简便方法，该方法可用于环丙基融合的吡咯烷，其中包含四个立体生成中心。醇与N-烷基-N-羟基酰胺的直接Mitsunobu反应的发展促进了合成，从而产生了重氮前体，在分子内进行环丙烷化后，得到了一个由N–O组成的含环丙基稠合双环中间体的文库。对该文库一个成员的N–O部分进行精细加工导致形成所需的吡咯烷环，这表明该方法可用于制备环丙基稠合的杂环。
• Aryl Radical Activation of C–O Bonds: Copper-Catalyzed Deoxygenative Difluoromethylation of Alcohols
  作者：Aijie Cai、Wenhao Yan、Wei Liu

  DOI：10.1021/jacs.1c04254

  日期：2021.7.7

  direct use of free alcohols without purification of the xanthate esters. Mechanistic studies are consistent with the hypothesis of aryl radicals being formed and initiating the cleavage of the C–O bonds of xanthate esters, to generate alkyl radicals as the key intermediates. This aryl radical activation approach represents a new strategy for the activation of alcohols as cross-coupling partners.

  鉴于其在天然产物和药物中的普遍存在，醇是构建 C-C 键最有吸引力的起始材料之一。我们在此报告了第一个利用芳基的反应性来激活醇衍生的黄原酸酯中的 C-O 键的催化策略，从而发现了第一个催化脱氧二氟甲基化反应。在铜催化条件下，很容易从醇原料合成的各种烷基黄原酸酯被催化生成的芳基活化，并通过烷基中间体转化为烷基二氟甲烷产物。这种可扩展的协议具有广泛的底物范围和官能团耐受性，能够对复杂的药剂进行后期修饰。已开发出一种一锅法，允许直接使用游离醇而无需纯化黄原酸酯。机理研究与芳基自由基形成并引发黄原酸酯的 C-O 键断裂以产生作为关键中间体的烷基自由基的假设一致。这种芳基自由基活化方法代表了一种将醇作为交叉偶联物活化的新策略。
• Molecular Determinants for the Activating/Blocking Actions of the 2<i>H</i>-1,4-Benzoxazine Derivatives, a Class of Potassium Channel Modulators Targeting the Skeletal Muscle K_ATP Channels
  作者：Domenico Tricarico、Antonietta Mele、Giulia Maria Camerino、Antonio Laghezza、Giuseppe Carbonara、Giuseppe Fracchiolla、Paolo Tortorella、Fulvio Loiodice、Diana Conte Camerino

  DOI：10.1124/mol.108.046615

  日期：2008.7

  The 2 H -1,4-benzoxazine derivatives are modulators of the skeletal muscle ATP-sensitive-K+ channels (KATP), activating it in the presence of ATP but inhibiting it in the absence of nucleotide. To investigate the molecular determinants for the activating/blocking actions of these compounds, novel molecules with different alkyl or aryl-alkyl substitutes at position 2 of the 1,4-benzoxazine ring were prepared. The effects of the lengthening of the alkyl chain and of branched substitutes, as well as of the introduction of aliphatic/aromatic rings on the activity of the molecules, were investigated on the skeletal muscle KATP channels of the rat, in excised-patch experiments, in the presence or absence of internal ATP (10-4 M). In the presence of ATP, the 2- n -hexyl analog was the most potent activator (DE50 = 1.08 × 10-10 M), whereas the 2-phenylethyl was not effective. The rank order of efficacy of the openers was 2- n -hexyl ≥2-cyclohexylmethyl >2-isopropyl = 2- n -butyl ≥ 2-phenyl ≥ 2-benzyl = 2-isobutyl analogs. In the absence of ATP, the 2-phenyl analog was the most potent inhibitor (IC50 = 2.5 × 10-11 M); the rank order of efficacy of the blockers was 2-phenyl ≥ 2- n -hexyl > 2- n -butyl > 2-cyclohexylmethyl, whereas the 2-phenylethyl, 2-benzyl, and 2-isobutyl 1,4-benzoxazine analogs were not effective; the 2-isopropyl analog activated the KATP channel even in the absence of nucleotide. Therefore, distinct molecular determinants for the activating or blocking actions for these compounds can be found. For example, the replacement of the linear with the branched alkyl substitutes at the position 2 of the 1,4-benzoxazine nucleus determines the molecular switch from blockers to openers. These compounds were 100-fold more potent and effective as openers than other KCO against the muscle KATP channels.

  2H-1,4-苯并恶嗪衍生物是骨骼肌ATP敏感性K+通道(KATP)的调节剂，在有ATP存在时激活它，而在无核苷酸存在时抑制它。为了研究这些化合物的激活/阻断作用的分子决定因素，制备了在1,4-苯并恶嗪环的2位上具有不同烷基或芳基-烷基取代基的新型分子。在切除-补丁实验中，在有或无内源性ATP(10-4M)存在的情况下，研究了延长烷基链、引入支链取代基以及引入脂肪/芳香环对这些分子在骨骼肌KATP通道上的活性的影响。在有ATP存在的情况下，2-正己基类似物是最有效的激活剂(DE50 = 1.08 × 10-10 M)，而2-苯乙基类似物则无效。开放剂的功效顺序为2-正己基 ≥2-环己基甲基 >2-异丙基 = 2-正丁基 ≥ 2-苯基 ≥ 2-苄基 = 2-异丁基类似物。在没有ATP存在的情况下，2-苯基类似物是最有效的抑制剂(IC50 = 2.5 × 10-11 M);阻断剂的功效顺序为2-苯基 ≥ 2-正己基 > 2-正丁基 > 2-环己基甲基，而2-苯乙基、2-苄基和2-异丁基1,4-苯并恶嗪类似物则无效;即使在无核苷酸存在的情况下，2-异丙基类似物也能激活KATP通道。因此，可以找到这些化合物激活或阻断作用的独特分子决定因素。例如，将1,4-苯并恶嗪核的2位上的线性烷基取代基替换为支链烷基取代基，决定了分子从阻断剂到开放剂的转换。这些化合物作为开放剂，比其他针对骨骼肌KATP通道的KCO具有100倍的更强效力和效果。
• Catalytic Staudinger Reduction at Room Temperature
  作者：Danny C. Lenstra、Joris J. Wolf、Jasmin Mecinović

  DOI：10.1021/acs.joc.9b00831

  日期：2019.5.17

  catalytic Staudinger reduction at room temperature that enables the preparation of a structurally diverse set of amines from azides in excellent yields. The reaction is based on the use of catalytic amounts of triphenylphosphine as a phosphine source and diphenyldisiloxane as a reducing agent. Our catalytic Staudinger reduction exhibits a high chemoselectivity, as exemplified by reduction of azides

  我们报道了在室温下有效的Staudinger催化还原反应，该反应能够以优异的收率从叠氮化物制备结构多样的胺。该反应基于催化量的三苯基膦作为膦源和二苯基二硅氧烷作为还原剂的使用。我们的Staudinger催化还原具有很高的化学选择性，例如叠氮化物相对于其他常见官能团（包括腈，烯烃，炔烃，酯和酮）的还原。
• Umpolung Strategy for Arene C−H Etherification Leading to Functionalized Chromanes Enabled by I(III) <i>N</i> ‐Ligated Hypervalent Iodine Reagents
  作者：Myriam Mikhael、Wentao Guo、Dean J. Tantillo、Sarah E. Wengryniuk

  DOI：10.1002/adsc.202100809

  日期：2021.11.9

  The direct formation of aryl C−O bonds via the intramolecular dehydrogenative coupling of a C−H bond and a pendant alcohol represents a powerful synthetic transformation. Herein, we report a method for intramolecular arene C−H etherification via an umpoled alcohol cyclization mediated by an I(III) N-HVI reagent. This approach provides access to functionalized chromane scaffolds from primary, secondary

  通过C-H键和侧醇的分子内脱氢偶联直接形成芳基C-O键代表了强大的合成转化。在此，我们报告了一种通过 I(III) N- HVI 试剂介导的 umpoled 醇环化进行分子内芳烃 C-H 醚化的方法。这种方法通过级联环化-碘盐形成从伯醇、仲醇和叔醇中获得官能化色满支架，后者为下游衍生化提供了通用的功能处理。计算研究支持通过 I(III) 配体交换初始形成 umpoled O-中间体，然后是竞争性直接和螺环化/1,2-转变途径。

表征谱图