(R)-1,3-diethyl 2-(2-nitro-1-phenylethyl)malonate

• 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: (R)-1,3-diethyl 2-(2-nitro-1-phenylethyl)malonate
• 英文别名: diethyl 2-(2-nitro-1-phenylethyl)malonate；(R)-ethyl 2-carboethoxy-4-nitro-3-phenylbutyrate；(R)-diethyl 2-(2-nitro-1-phenylethyl)malonate；diethyl (R)-2-(2-nitro-1-phenylethyl)malonate；ethyl 2-carboethoxy-4-nitro-3-phenylbutyrate；ethyl(R)-2-ethoxycarbonyl-4-nitro-3-phenylbutanoate；diethyl 2-[(1R)-2-nitro-1-phenylethyl]propanedioate
• 化学式: C₁₅H₁₉NO₆
• 分子量: 309.319
• InChiKey: VQKSJEVJSPWVIE-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  98.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-1,3-diethyl 2-(2-nitro-1-phenylethyl)malonate 在 氢气 、 sodium hydride 、 potassium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 异丙醇 、 甲苯 为溶剂， 80.0 ℃ 、3.04 MPa 条件下， 反应 15.5h， 生成 ethyl [(4R)-2-oxo-4-phenylpyrrolidin-1-yl]acetate
  参考文献：
  名称：

  Enantioselective synthesis of γ-aminobutyric acid derivatives by Ni(II)-catalyzed reaction of diethyl malonate with nitroalkenes

  摘要：

  A new synthetic approach to (3R)-4-amino-3-methylbutyric acid and [(4R)-2-oxo-4-phenylpyrrolidin-1-yl]acetamide [(R)-phenotropil] has been developed. Asymmetric center with a required configuration has been generated via enantioselective addition of diethyl malonate to 1-nitropropene and beta-nitrostyrene, catalyzed by Ni(II) complexes with (R,R)- and (S,S)-N,N'-dibenzylcyclohexane-1,2-diamine.

  DOI：

  10.1134/s1070428013050047
• 作为产物：
  描述：

  苯甲醛 在 C₁₂₁H₁₃₆N₈O₈⁽⁴⁺⁾*4Br^(1-) 、 三乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 1.5h， 生成 (R)-1,3-diethyl 2-(2-nitro-1-phenylethyl)malonate
  参考文献：
  名称：

  基于金鸡纳生物碱的手性催化剂可作为高效多功能有机催化剂，用于将丙二酸酯不对称共轭加成到硝基烯烃中†

  摘要：

  制备了新的用作有机催化剂的季戊四醇四溴化物基手性季铵盐（7a和7b），并将其用作在温和的反应条件下（例如较低的碱和重金属的浓度）各种硝基烯烃和Michael供体（丙二酸酯）之间的对映选择性Michael加成反应的有机催化剂。催化剂和室温，化学收率非常好（高达97％）和ee的化学收率（高达99％）。

  DOI：

  10.1039/c5ob01351h

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。
• Supported and Unsupported Chiral Squaramides as Organocatalysts for Stereoselective Michael Additions: Synthesis of Enantiopure Chromenes and Spirochromanes
  作者：José M. Andrés、Jorge Losada、Alicia Maestro、Patricia Rodríguez-Ferrer、Rafael Pedrosa

  DOI：10.1021/acs.joc.7b01177

  日期：2017.8.18

  Novel supported chiral bifunctional squaramides have been easily prepared starting from diamines derived from natural amino acids and commercially available aminoalkyl polystyrene resins. These squaramides behave as excellent stereoselective recoverable organocatalysts in different Michael additions, in neat conditions at room temperature. The reaction on 2-(2-nitrovinyl) phenol as electrophile lead

  从衍生自天然氨基酸的二胺和可商购的氨基烷基聚苯乙烯树脂开始，已经容易地制备了新型的负载性手性双官能方酸酰胺。在室温下的纯净条件下，这些麦角酰胺在不同的迈克尔添加量下均表现为出色的立体选择性可回收有机催化剂。以2-（2-硝基乙烯基）苯酚为亲电试剂，以优异的收率和对映选择性，反应生成易于转化为4 H-色烯和螺并二氢吡喃酮的中间体。
• Bifunctional Hydrogen-Bond Donors That Bear a Quinazoline or Benzothiadiazine Skeleton for Asymmetric Organocatalysis
  作者：Tsubasa Inokuma、Masaya Furukawa、Takuya Uno、Yusuke Suzuki、Kohzo Yoshida、Yoshiaki Yano、Katsumi Matsuzaki、Yoshiji Takemoto

  DOI：10.1002/chem.201101338

  日期：2011.9.5

  (HB)‐donor catalysts that bear a 2‐aminoquinazolin‐4‐(1H)‐one or a 3‐aminobenzothiadiazine‐1,1‐dioxide skeleton have been developed, and it has been shown that these catalyst motifs act similarly to other HB‐donor catalysts such as thioureas. The highly enantioselective hydrazination of 1,3‐dicarbonyl compounds was realized even at room temperature with up to 96 % ee for 2‐aminoquinazolin‐4‐(1H)‐one‐type

  已开发出带有2-氨基喹唑啉-4-（1 H）-one或3-氨基苯并噻二嗪-1,1-二氧化物骨架的氢键（HB）供体催化剂，并且已证明这些催化剂基序起作用与其他HB-施主催化剂（如硫脲）相似。1,3-二羰基化合物的高度对映选择性肼化反应即使在室温下也能达到2-氨基喹唑啉-4-（1 H）的96％  ee一类催化剂，比相应的尿素和硫脲催化剂更有效。此外，苯并噻二嗪-1,1-二氧化物型催化剂还显示出可以以高对映选择性促进炔酸酯向烯丙酸酯的异构化。为克服产物以与起始炔酸酯的混合物形式获得的问题，我们开发了炔酸酯的串联异构化和环加成反应，以合成高级手性化合物，如双环[2.2.1]庚烯和3-亚烷基吡咯烷，而不会造成重大损失对映选择性。
• Organocatalyzed asymmetric Michael addition by an efficient bifunctional carbohydrate–thiourea hybrid with mechanistic DFT analysis
  作者：Chandra S. Azad、Imran A. Khan、Anudeep K. Narula

  DOI：10.1039/c6ob02158a

  日期：——

  core scaffold were synthesized and examined as catalysts for the asymmetric Michael addition reaction of aryl/alkyl trans-β-nitrostyrenes over cyclohexanone and other Michael donors having active methylene. Excellent enantioselectivities (<95%), diastereoselectivities (<99%), and yields (<99%) were attained under solvent free conditions using 10 mol% of 1d0. The obtained results were explained through

  合成了一系列以D-葡萄糖为核心骨架的硫脲基双功能有机催化剂，并研究了其作为芳基/烷基反式-β-硝基苯乙烯在环己酮和其他具有活性亚甲基的迈克尔供体上的不对称迈克尔加成反应的催化剂。在无溶剂条件下，使用10 mol％的1d 0可获得极好的对映选择性（<95％），非对映选择性（<99％）和产率（<99％）。通过使用B3LYP / 6-311G（d，p）// B3LYP / 6-31G（d）基本集的DFT计算来解释获得的结果。QM / MM计算揭示了在速率确定步骤中环己酮作为溶剂和反应物的作用，赋予了31.91 kcal mol -1 能量形成产品。
• Microwave-Assisted Synthesis of Guanidine Organocatalysts Bearing a Tetrahydroisoquinoline Framework and Their Evaluation in Michael Addition Reactions
  作者：Tricia Naicker、Per I. Arvidsson、Hendrik G. Kruger、Glenn E. M. Maguire、Thavendran Govender

  DOI：10.1002/ejoc.201200303

  日期：2012.6

  simple and practical syntheses of chiral guanidine organocatalysts and their evaluation in the asymmetric Michael addition reaction of malonates and beta-keto esters with nitro-olefins is reported. These organocatalysts are the first of their kind based on a tetrahydroisoquinoline framework. In addition, a microwave-assisted procedure for introducing the guanidine unit onto amino amide derivatives is reported

  报道了手性胍有机催化剂的简单实用合成及其在丙二酸酯和β-酮酯与硝基烯烃的不对称迈克尔加成反应中的评价。这些有机催化剂是同类中第一个基于四氢异喹啉骨架的催化剂。此外，还报道了将胍单元引入氨基酰胺衍生物的微波辅助程序。获得的手性产物具有定量化学效率（高达 99% 的产率）和出色的对映选择性（高达 97% ee）。