methyl (S)-2-carbomethoxy-2-methyl-4-nitro-3-phenylbutyrate | 620960-37-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl (S)-2-carbomethoxy-2-methyl-4-nitro-3-phenylbutyrate
• 英文别名: (S)-methyl 2-carbomethyloxy-2-methyl-4-nitro-3-phenylbutyrate；dimethyl (R)-2-methyl-2-(1-phenyl-2-nitroethyl)malonate；dimethyl 2-methyl-2-(2-nitro-1-phenylethyl)malonate；dimethyl 2-methyl-2-[(1S)-2-nitro-1-phenylethyl]propanedioate
• CAS: 620960-37-4
• 化学式: C₁₄H₁₇NO₆
• 分子量: 295.292
• InChiKey: OYOXTHBZLIBQBW-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  98.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  反式硝基苯乙烯 、 甲基丙二酸二甲酯 在 2-CH₂NHC(=NMe)NHCH₂-2' 、 substituted (Ra)-1,1'-binaphthyl 作用下， 以 乙醚 为溶剂， 反应 12.0h， 以82%的产率得到methyl (S)-2-carbomethoxy-2-methyl-4-nitro-3-phenylbutyrate
  参考文献：
  名称：

  轴向手性胍作为对映选择性碱催化剂，用于 1,3-二羰基化合物与共轭硝基烯烃的 1,4-加成反应

  摘要：

  提出了一种设计手性胍分子的新策略，其特点是引入了轴向手性联萘骨架。由此开发的轴向手性胍催化剂促进了 1,3-二羰基化合物与多种共轭硝基烯烃的高度对映选择性 1,4-加成反应，并显示出极高的催化活性。

  DOI：

  10.1021/ja057848d

文献信息

• The Amino Thiourea-Catalyzed Asymmetric Nucleophilic Reactions
  作者：Yoshiji Takemoto、Hideto Miyabe

  DOI：10.2533/chimia.2007.269

  日期：——

  Bifunctional amino thiourea-catalyzed asymmetric additions of several nucleophiles into electron-deficient unsaturated compounds such as nitroolefins, ?,?-unsaturated imides, imines, and azodicarboxylates are described. We discovered that bifunctional thioureas bearing a tertiary amino group significantly accelerated several nucleophilic addition reactions of active methylene compounds to electron-deficient double bonds. In these reactions, a strong hydrogen-bonding ability of the thiourea moiety as well as an appropriate Brønsted basicity of the tertiary amine is crucial for high enantioselectivity. This dual activation of both nucleophiles and electrophiles by the bifunctional thiourea expanded the applicability of the thiourea-catalyzed enantioselective reaction. In addition, these organocatalyzed asymmetric reactions were successfully applied to the concise asymmetric synthesis of natural products and medicinal candidates such as epibatidine, baclofen, and CP-99,994.

  双功能氨基硫脲催化的不对称加成反应将几种亲核试剂加入到电子不足的不饱和化合物中，如硝基烯烃、α，β-不饱和亚酰胺、亚胺和叠氮二羧酸酯。我们发现，含有三级胺基的双功能硫脲显著加速了活性亚甲基化合物与电子不足双键的几种亲核加成反应。在这些反应中，硫脲基团的强氢键能力以及三级胺的适当Brønsted碱性对高对映选择性至关重要。双功能硫脲对亲核试剂和电子亲电试剂的双重活化扩展了硫脲催化的不对称反应的适用范围。此外，这些有机催化的不对称反应成功应用于天然产物和药用候选化合物的简洁不对称合成，如蛙毒碱、氯硝西泮和CP-99,994。
• Bifunctional Thioureas with α-Trifluoromethyl or Methyl Groups: Comparison of Catalytic Performance in Michael Additions
  作者：Eddy I. Jiménez、Wilmer E. Vallejo Narváez、Carlos A. Román-Chavarría、Josue Vazquez-Chavez、Tomás Rocha-Rinza、Marcos Hernández-Rodríguez

  DOI：10.1021/acs.joc.6b01063

  日期：2016.9.2

  Thioureas are an important scaffold in organocatalysis because of their ability to form hydrogen bonds that activate substrates and fix them in a defined position, which allows a given reaction to occur. Structures that enhance the acidity of the thiourea are usually used to increase the hydrogen-bonding properties, such as 3,5-bis(trifluoromethyl)phenyl and boronate ureas. Herein, we report the synthesis

  硫脲是有机催化中的重要支架，因为它们能够形成氢键，从而激活底物并将其固定在确定的位置，从而使给定的反应发生。通常使用增强硫脲酸度的结构来增加氢键合性能，例如3,5-双（三氟甲基）苯基和硼酸酯脲。本文中，我们报道了具有手性部分的双功能硫脲的合成，该手性部分包括三氟甲基或甲基。他们在代表性的迈克尔加成反应中的催化性能用于比较甲基上氟化的电子效应。观察到的关于产量和ee值的差异不能仅归因于不同的空间环境；理论结果表明在相应的过渡态内有明显的相互作用。计算得出的过渡态表明，氟化催化剂具有更强的N–H···O和C–H···F氢键，而非氟化体系则具有C–H···π接触。这些结果表明，各种氢键相互作用对于确定硫脲有机催化的产率和选择性很重要。这些细节可以在催化剂设计中进一步利用。
• Scope and Mechanism of Enantioselective Michael Additions of 1,3-Dicarbonyl Compounds to Nitroalkenes Catalyzed by Nickel(II)−Diamine Complexes
  作者：David A. Evans、Shizue Mito、Daniel Seidel

  DOI：10.1021/ja0735913

  日期：2007.9.1

  Readily prepared Ni(II)-bis[(R,R)-N,N'-dibenzylcyclohexane-1,2-diamine]Br(2) was shown to catalyze the Michael addition of 1,3-dicarbonyl compounds to nitroalkenes at room temperature in good yields with high enantioselectivities. The two diamine ligands in this system each play a distinct role: one serves as a chiral ligand to provide stereoinduction in the addition step while the other functions

  容易制备的 Ni(II)-双[(R,R)-N,N'-二苄基环己烷-1,2-二胺]Br(2) 在室温下可催化 1,3-二羰基化合物与硝基烯烃的迈克尔加成反应温度高，产率高，对映选择性高。该系统中的两个二胺配体各自发挥不同的作用：一个作为手性配体在加成步骤中提供立体诱导，而另一个作为底物烯醇化的基础。还研究了催化剂内的配体改性，以促进脂肪族硝基烯烃、1,3-二酮和 β-酮酸的反应。Ni(II)-双[(R,R)-N,N'-di-p-bromo-benzylcyclohex-1,2-diamine]Br(2) 在这些情况下被发现是一种有效的催化剂。此外，单二胺络合物，Ni(II)-[(R,R)-N,N'-二苄基环己烷-1,2-二胺]Br(2)，在水存在下催化加成反应。所提出的立体化学诱导模型显示与 X 射线结构分析一致。
• Supported bifunctional thioureas as recoverable and reusable catalysts for enantioselective nitro-Michael reactions
  作者：José M Andrés、Miriam Ceballos、Alicia Maestro、Isabel Sanz、Rafael Pedrosa

  DOI：10.3762/bjoc.12.61

  日期：——

  The catalytic activity of different supported bifunctional thioureas on sulfonylpolystyrene resins has been studied in the nitro-Michael addition of different nucleophiles to trans-β-nitrostyrene derivatives. The activity of the catalysts depends on the length of the tether linking the chiral thiourea to the polymer. The best results were obtained with the thiourea derived from (L)-valine and 1,6-hexanediamine. The catalysts can be used in only 2 mol % loading, and reused for at least four cycles in neat conditions. The ball milling promoted additions also worked very well.

  不同支撑的双官能硫脲在磺酰基聚苯乙烯树脂上的催化活性已经在不同亲核试剂对反式-β-硝基苯乙烯衍生物的硝基迈克尔加成中进行了研究。催化剂的活性取决于将手性硫脲与聚合物连接的链长度。最佳结果是使用由(L)-缬氨酸和1,6-己二胺衍生的硫脲得到的。催化剂可以在仅2%的负载下使用，并在纯净条件下至少重复使用四个周期。球磨促进的加成也非常有效。
• Organocatalytic Stereoselective Synthesis of Acyclic γ-Nitrothioesters with All-Carbon Quaternary Stereogenic Centers
  作者：Yukihiro Arakawa、Sven P. Fritz、Helma Wennemers

  DOI：10.1021/jo500403q

  日期：2014.5.2

  stereoselective synthesis of acyclic thioesters bearing adjacent quaternary and tertiary stereogenic centers under mild organocatalytic conditions was developed. α-Substituted monothiomalonates (MTMs) were used as thioester enolate equivalents. They reacted cleanly with nitroolefins in the presence of 1–6 mol % of cinchona alkaloid urea derivatives, and provided access to γ-nitrothioesters with quaternary stereocenters

  提出了在温和的有机催化条件下立体选择性合成带有相邻季铵和叔立体中心的无环硫酯的方法。用α-取代的单硫代丙二酸酯（MTM）作为硫酯烯酸酯等效物。它们在1–6 mol％的金鸡纳生物碱尿素衍生物存在下与硝基烯烃干净地反应，并以高收率和非对映和对映选择性提供了具有季立体中心的γ-硝基硫代酯的通道。机械研究提供了确定立体选择性的参数的见解，并表明非对映选择性可以通过MTM底物的性质来控制。三种官能团（氧酸酯，硫酯，