(S)-2-(1-(4-fluorophenyl)-3-oxo-3-phenylpropyl)malononitrile | 1316231-51-2

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物
• 英文名称: (S)-2-(1-(4-fluorophenyl)-3-oxo-3-phenylpropyl)malononitrile
• 英文别名: 2-[(1S)-1-(4-fluorophenyl)-3-oxo-3-phenylpropyl]propanedinitrile
• CAS: 1316231-51-2
• 化学式: C₁₈H₁₃FN₂O
• 分子量: 292.312
• InChiKey: ZCTYZVLWSCGDSY-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  64.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-2-(1-(4-fluorophenyl)-3-oxo-3-phenylpropyl)malononitrile 在 盐酸 、 氯化亚砜 作用下， 以 甲苯 为溶剂， 反应 12.0h， 生成
  参考文献：
  名称：

  Chloramphenicol base chemistry. Part 11: 1 chloramphenicol base-derived thiourea-catalyzed enantioselective Michael addition of malononitrile to α , β -unsaturated ketones

  摘要：

  The first chloramphenicol base-derived thiourea-catalyzed enantioselective Michael addition of malononitrile to alpha,beta-unsaturated ketones is reported. The Michael adducts were obtained in good to excellent yields (up to 98% yield) and enantioselectivities (up to 94% ee). This reaction has a broad substrate scope to various alpha,beta-unsaturated ketones. With this in mind, this methodology was successfully applied to the synthesis of a chiral piperidone, an advanced building block for dihydropyridinone P2X(7) receptor antagonists. (C) 2017 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tetasy.2017.05.015
• 作为产物：
  描述：

  对氟苯甲醛 在 1-[3,5-bis(trifluoromethyl)phenyl]-3-[(1S,2R)-3-[tert-butyl(dimethyl)silyl]oxy-1-(dimethylamino)-1-(4-nitrophenyl)propan-2-yl]thiourea 作用下， 以 甲苯 为溶剂， 反应 168.0h， 生成 (S)-2-(1-(4-fluorophenyl)-3-oxo-3-phenylpropyl)malononitrile
  参考文献：
  名称：

  Chloramphenicol base chemistry. Part 11: 1 chloramphenicol base-derived thiourea-catalyzed enantioselective Michael addition of malononitrile to α , β -unsaturated ketones

  摘要：

  The first chloramphenicol base-derived thiourea-catalyzed enantioselective Michael addition of malononitrile to alpha,beta-unsaturated ketones is reported. The Michael adducts were obtained in good to excellent yields (up to 98% yield) and enantioselectivities (up to 94% ee). This reaction has a broad substrate scope to various alpha,beta-unsaturated ketones. With this in mind, this methodology was successfully applied to the synthesis of a chiral piperidone, an advanced building block for dihydropyridinone P2X(7) receptor antagonists. (C) 2017 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tetasy.2017.05.015

文献信息

• Highly Enantioselective Kinetic Resolution of Michael Adducts through N-Heterocyclic Carbene Catalysis: An Efficient Asymmetric Route to Cyclohexenes
  作者：Xiang-Yu Chen、Sun Li、Qiang Liu、Mukesh Kumar、Anssi Peuronen、Kari Rissanen、Dieter Enders

  DOI：10.1002/chem.201802420

  日期：2018.7.11

  A highly efficient strategy for the kinetic resolution of Michael adducts was realized using a chiral N‐heterocyclic carbene catalyst. The kinetic resolution provides a new convenient route to single diastereomers of cyclohexenes and Michael adducts in good yields with high enantiomeric excesses (up to 99 % ee with a selectivity factor of up to 458). This “two flies with one swat” concept allows the

  使用手性N-杂环卡宾催化剂实现了迈克尔加合物动力学拆分的高效策略。动力学拆分提供了一条新的便捷途径，可以以高收率和高对映异构体过量（高达99％ee，选择性因子高达458）获得环己烯和迈克尔加合物的单一非对映异构体。这种“两只苍蝇一拍打”的概念允许通过一次转换同时合成这两种具有合成价值的化合物类别。
• Squaramide-catalyzed enantioselective Michael addition of malononitrile to chalcones
  作者：Wen Yang、Yang Jia、Da-Ming Du

  DOI：10.1039/c1ob06302b

  日期：——

  A highly enantioselective Michael addition of malononitrile to chalcones catalyzed by a chiral quinine-derived squaramide catalyst has been developed. This organocatalytic reaction at a very low catalyst loading (0.5 mol%) led to chiral γ-cyano carbonyl compounds in good yields with high enantioselectivities (up to 96% ee) under mild reaction conditions.

  对映体的高对映选择性迈克尔加成 丙二腈已经开发了由手性奎宁衍生的方酰胺催化剂催化的查耳酮。在非常低的催化剂负载量（0.5摩尔％）下，这种有机催化反应在温和的反应条件下以高收率和高对映选择性（最高96％ee）产生了手性的γ-氰基羰基化合物。
• Mesoporous SBA-15 with Short Mesochannels Immobilized Natural Quinine for Asymmetric Michael Addition of Chalcones
  作者：Qiu Chen、Cui Xin、Lan-Lan Lou、Kai Yu、Fei Ding、Shuangxi Liu

  DOI：10.1007/s10562-011-0648-5

  日期：2011.9

  approach for asymmetric organocatalysed Michael addition of malononitrile to chalcones. The catalytic activity was greatly enhanced, compared with the conventional analogue. Furthermore, the enantioselectivity could also be significantly improved for all substrates.Graphical AbstractNatural quinine was firstly immobilized on mesoporous SBA-15 with short mesochannels for the heterogeneous asymmetric Michael

  一种负载在短介孔 SBA-15 上的天然奎宁多相催化剂最初是通过一种简单的共缩合方法合成的，用于不对称有机催化迈克尔加成丙二腈到查耳酮。与传统类似物相比，催化活性大大提高。此外，对所有底物的对映选择性也可以显着提高。图文摘要天然奎宁首先固定在具有短介通道的介孔SBA-15上，用于丙二腈与查耳酮的异质不对称迈克尔加成。与传统类似物相比，催化活性和对映选择性都大大提高。
• Organocatalytic Enantioselective Decarboxylative Michael Addition of β-Keto Acids to Dicyanoolefins and Disulfonylolefins
  作者：Yi Wei、Ran Guo、Yanfeng Dang、Jing Nie、Jun-An Ma

  DOI：10.1002/adsc.201600485

  日期：2016.9.1

  A convenient organocatalytic enantioselective decarboxylative Michael addition of β‐keto acids to dicyanoolefins and disulfonylolefins is realized. In the presence of saccharide‐derived chiral amino thioureas, the reaction proceeded smoothly to afford a wide range of the Michael adducts in 62–99% yield with 70–94% ee. Moreover, one of the chiral adducts obtained could be readily converted into the

  实现了将β-酮酸方便地有机催化对映选择性脱羧迈克尔加成到二氰基烯烃和二磺酰基烯烃中。在糖衍生的手性氨基硫脲的存在下，反应顺利进行，以62-99％的收率和70-94％ee的收率提供了多种迈克尔加合物。此外，所获得的手性加合物之一可以容易地在四个步骤中以85％ee转化为单氟化产物，总产率为68％。
• Enantioselective Michael Addition of Malononitrile to Unsaturated Ketones Catalyzed by Rare-Earth Metal Amides RE[N(SiMe₃)₂]₃ with Phenoxy-Functionalized TsDPEN Ligands
  作者：Yingying Ren、Qishun Yu、Chengrong Lu、Bei Zhao

  DOI：10.1021/acs.joc.3c01435

  日期：2023.9.15

  The catalytic enantioselective Michael addition of α,β-unsaturated ketones with malononitrile was well established using rare-earth metal amides RE[N(SiMe3)2]3 (RE = Y, Eu, Sm, Nd, La) with chiral phenoxy-functionalized TsDPEN ligands. The combination of lanthanum amide La[N(SiMe3)2]3 and chiral TsDPEN ligand H3L1 [H3L1 = N-((1R,2R)-2-((3,5-di-tert-butyl-2-hydroxybenzyl)amino)-1,2-diphenylethyl)-4

  使用稀土金属酰胺 RE[N(SiMe 3 ) 2 ] 3 (RE = Y, Eu, Sm, Nd, La) 和手性苯氧基，很好地建立了 α,β-不饱和酮与丙二腈的催化对映选择性迈克尔加成反应。功能化的 TsDPEN 配体。酰胺镧 La[N(SiMe 3 ) 2 ] 3与手性 TsDPEN 配体 H 3 L 1 [H 3 L 1 = N -((1 R ,2 R )-2-((3,5-di-)叔丁基-2-羟基苄基)氨基)-1,2-二苯基乙基)-4-甲基苯磺酰胺]以1:1.5的摩尔比被证明是THF的最佳配合物，它以优异的产率提供了所需的β-羰基二腈-15 °C 12 小时后具有良好至高的对映选择性。