2-[hydroxy(2-methoxyphenyl)methyl]acrylic acid ethyl ester

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-[hydroxy(2-methoxyphenyl)methyl]acrylic acid ethyl ester
• 英文别名: ethyl 2-((hydroxy)(2-methoxyphenyl)methyl)acrylate；Ethyl 2-(Hydroxy(2-Methoxyphenyl)Methyl)Acrylate；ethyl 2-[hydroxy-(2-methoxyphenyl)methyl]prop-2-enoate
• 化学式: C₁₃H₁₆O₄
• 分子量: 236.268
• InChiKey: QOZCPFVDPFSTDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[hydroxy(2-methoxyphenyl)methyl]acrylic acid ethyl ester 在 三乙胺 作用下， 以 乙醚 为溶剂， 反应 0.33h， 生成 ethyl (Z)-2-[(dimethoxyphosphoryl)methyl]-3-(2-methoxyphenyl)-2-propenoate
  参考文献：
  名称：

  Asymmetric synthesis of 2-alkyl-3-phosphonopropanoic acid derivatives via Rh-catalyzed asymmetric hydrogenation

  摘要：

  The commercially available ferrocene-based diphosphine ligand (S-c,S-Fc)-TaniaPhos was found to be highly effective in the Rh-catalyzed asymmetric hydrogenation of 3-aryl-2-(phosphonomethyl)propenates. Excellent enantioselectivity (90-98% ee) and high catalytic activity (S/C up to 1000) have been achieved, which represents the best results reported so far. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2011.12.002
• 作为产物：
  描述：

  邻甲氧基苯甲醛 、 丙烯酸乙酯 在 奎宁环-3-醇 、 ytterbium(III) triflate 作用下， 以 formamide 为溶剂， 反应 12.0h， 以90%的产率得到2-[hydroxy(2-methoxyphenyl)methyl]acrylic acid ethyl ester
  参考文献：
  名称：

  在极性溶剂（水和甲酰胺）中Baylis-Hillman反应的速率加速。暗示了氢键的主要作用，而不是疏水作用。

  摘要：

  当反应在水中进行时，已观察到环己烯酮和苯甲醛之间的Baylis-Hillman反应大大加速。测试了几种不同的胺催化剂，并且与在不存在溶剂的情况下进行的反应一样，就速率而言，发现3-羟基喹核苷是最佳催化剂。该反应已经扩展到包括醛的其他醛亲电试剂。尝试将这项工作扩展至丙烯酸酯仅获得了部分成功，因为在碱催化和水促进的条件下，丙烯酸甲酯和丙烯酸乙酯迅速水解。然而，丙烯酸叔丁酯足够稳定以与相对反应性的亲电试剂偶联。有关使用极性溶剂的进一步研究表明，甲酰胺还提供了显着的加速作用，并且使用5当量的甲酰胺（最适量）比在水中进行的反应速率更快。使用甲酰胺，在Yb（OTf）（3）（5 mol％）的存在下实现了进一步的加速。新条件的范围用一系列迈克尔受体和苯甲醛以及一系列亲电试剂和丙烯酸乙酯进行了测试。讨论了速率加速的起源。

  DOI：

  10.1021/jo016073y

文献信息

• Rate Acceleration of the Baylis−Hillman Reaction in Polar Solvents (Water and Formamide). Dominant Role of Hydrogen Bonding, Not Hydrophobic Effects, Is Implicated
  作者：Varinder K. Aggarwal、David K. Dean、Andrea Mereu、Richard Williams

  DOI：10.1021/jo016073y

  日期：2002.1.1

  A substantial acceleration of the Baylis-Hillman reaction between cyclohexenone and benzaldehyde has been observed when the reaction is conducted in water. Several different amine catalysts were tested, and as with reactions conducted in the absence of solvent, 3-hydroxyquinuclidine was found to be the optimum catalyst in terms of rate. The reaction has been extended to other aldehyde electrophiles

  当反应在水中进行时，已观察到环己烯酮和苯甲醛之间的Baylis-Hillman反应大大加速。测试了几种不同的胺催化剂，并且与在不存在溶剂的情况下进行的反应一样，就速率而言，发现3-羟基喹核苷是最佳催化剂。该反应已经扩展到包括醛的其他醛亲电试剂。尝试将这项工作扩展至丙烯酸酯仅获得了部分成功，因为在碱催化和水促进的条件下，丙烯酸甲酯和丙烯酸乙酯迅速水解。然而，丙烯酸叔丁酯足够稳定以与相对反应性的亲电试剂偶联。有关使用极性溶剂的进一步研究表明，甲酰胺还提供了显着的加速作用，并且使用5当量的甲酰胺（最适量）比在水中进行的反应速率更快。使用甲酰胺，在Yb（OTf）（3）（5 mol％）的存在下实现了进一步的加速。新条件的范围用一系列迈克尔受体和苯甲醛以及一系列亲电试剂和丙烯酸乙酯进行了测试。讨论了速率加速的起源。
• Enantioselective Rh-Catalyzed Hydrogenation of 3-Aryl-2-phosphonomethylpropenoates by a New Class of Chiral Ferrocenyl Diphosphine Ligands
  作者：Dao-Yong Wang、Xiang-Ping Hu、Chuan-Jin Hou、Jun Deng、Sai-Bo Yu、Zheng-Chao Duan、Jia-Di Huang、Zhuo Zheng

  DOI：10.1021/ol9012469

  日期：2009.8.6

  A new class of chiral ferrocenyl diphosphine ligands with an imidazole ring, (Rc,SFc)-ImiFerroPhos, has been prepared from acylferrocenes through a five-step transformation and successfully applied in the Rh-catalyzed asymmetric hydrogenation of various 3-aryl-substituted 2-phosphonomethylpropenoates, in which a series of chiral 3-phosphono-2-arylmethylpropanoic acid derivatives were achieved in ee

  新型的具有咪唑环的手性二茂铁基二膦配体（R c，S Fc）-ImiFerroPhos通过五步转化由酰基二茂铁制备，并成功地用于Rh催化的各种3-芳基-不对称加氢反应取代的2-膦酰基甲基丙酸酯，其中一系列手性3-膦酰基-2-芳基甲基丙酸衍生物的ee值高达98％。
• Electrophilic Warhead-Based Design of Compounds Preventing NLRP3 Inflammasome-Dependent Pyroptosis
  作者：Mattia Cocco、Davide Garella、Antonella Di Stilo、Emily Borretto、Livio Stevanato、Marta Giorgis、Elisabetta Marini、Roberto Fantozzi、Gianluca Miglio、Massimo Bertinaria

  DOI：10.1021/jm501072b

  日期：2014.12.26

  Pyroptosis is a caspase-1-dependent pro-inflammatory form of programmed cell death implicated in the pathogenesis of autoinflammatory diseases as well as in disorders characterized by excessive cell death and inflammation. Activation of NLRP3 inflammasome is a key event in the pyroptotic cascade. In this study, we describe the synthesis and chemical tuning of alpha,beta-unsaturated electrophilic warheads toward the development of antipyroptotic compounds. Their pharmacological evaluation and structure-activity relationships are also described. Compound 9 was selected as a model of this series, and it proved to be a reactive Michael acceptor, irreversibly trapping thiol nucleophiles, which prevented both ATP- and nigericin-triggered pyroptosis of human THP-1 cells in a time- and concentration-dependent manner. Moreover, 9 and other structurally related compounds, inhibited caspase-1 and NLRP3 ATPase activities. Our findings can contribute to the development of covalent, multitarget antipyroptotic compounds targeting molecular components of the NLRP3 inflammasome regulatory pathway.
• Asymmetric synthesis of 2-alkyl-3-phosphonopropanoic acid derivatives via Rh-catalyzed asymmetric hydrogenation
  作者：Li-Bin Luo、Dao-Yong Wang、Xiao-Mao Zhou、Zhuo Zheng、Xiang-Ping Hu

  DOI：10.1016/j.tetasy.2011.12.002

  日期：2011.12

  The commercially available ferrocene-based diphosphine ligand (S-c,S-Fc)-TaniaPhos was found to be highly effective in the Rh-catalyzed asymmetric hydrogenation of 3-aryl-2-(phosphonomethyl)propenates. Excellent enantioselectivity (90-98% ee) and high catalytic activity (S/C up to 1000) have been achieved, which represents the best results reported so far. (C) 2011 Elsevier Ltd. All rights reserved.
• Bifunctional Lewis Base Catalyzed Asymmetric <i>N</i>-Allylic Alkylation of 2-Hydroxypyridines
  作者：Fei-Ruo Zhang、Fanshu Cao、Kui Liu、Yi-Ping He、Gen Luo、Zhi-Shi Ye

  DOI：10.1021/acs.orglett.2c03207

  日期：2022.12.2

  A chiral Lewis base catalyzed enantioselective N-allylic alkylation of 2-hydroxypyridines and MBH carbonates is documented, affording a convenient access to N-alkylated 2-pyridones with up to 99% ee and 99% yield. Experimental and computational studies have revealed that the strong hydrogen bond interaction between the chiral Lewis base catalyst and 2-hydroxypyridines plays a crucial role in this reaction

  记录了手性路易斯碱催化的 2-羟基吡啶和 MBH 碳酸酯的对映选择性N-烯丙基烷基化，提供了一种方便地获得N-烷基化 2-吡啶酮的途径，其 ee 高达 99%，产率高达 99%。实验和计算研究表明，手性路易斯碱催化剂与 2-羟基吡啶之间的强氢键相互作用对该反应的反应性、化学选择性和对映选择性起着至关重要的作用。