diethyl 2-benzyl-2-(prop-2-yn-1-yl)malonate | 288632-71-3

• 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: diethyl 2-benzyl-2-(prop-2-yn-1-yl)malonate
• 英文别名: Ethyl 2-benzyl-2-carboethoxypent-4-ynoate；diethyl 2-benzyl-2-prop-2-ynylpropanedioate
• CAS: 288632-71-3
• 化学式: C₁₇H₂₀O₄
• 分子量: 288.343
• InChiKey: FOHUZNGOUVNMHF-UHFFFAOYSA-N

物化性质

• 熔点：
  50-51 °C
• 沸点：
  386.0±42.0 °C(Predicted)
• 密度：
  1.102±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  diethyl 2-benzyl-2-(prop-2-yn-1-yl)malonate 在 sodium hydroxide 作用下， 以 乙醚 为溶剂， 以51 %的产率得到2-benzyl-2-(ethoxycarbonyl)pent-4-ynoic acid
  参考文献：
  名称：

  通过电子供体-受体光活化进行炔烃的氟磺酰基芳基化

  摘要：

  公开了通过由日光或蓝色发光二极管驱动的电子供体-受体光活化，以硫酰氯氟化物作为FSO 2自由基前体对炔烃进行自由基氟磺酰基芳基化。在没有任何外部催化剂或添加剂的情况下，在温和的条件下，通过简单的操作制备了一系列有价值的苯并稠合碳环和杂环。该方案的合成潜力进一步证明了出色的可扩展性，以及多样化的后衍生化，包括 SuFEx 反应和其他有用的级联反应。

  DOI：

  10.1021/acs.orglett.4c01024
• 作为产物：
  描述：

  氯化苄 、 alkaline earth salt of/the/ methylsulfuric acid 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 生成 diethyl 2-benzyl-2-(prop-2-yn-1-yl)malonate
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationships of Haloenol Lactones:  Site-Directed and Isozyme-Selective Glutathione S-Transferase Inhibitors

  摘要：

  Overexpression of glutathione S-transferase (GST), particularly the GST-pi isozyme, has been proposed to be one of the biochemical mechanisms responsible for drug resistance in cancer chemotherapy, and inhibition of overexpressed GST has been suggested as an approach to combat GST-induced drug resistance. 3-Cinnamyl-5(E)-bromomethylidenetetrahydro-2-furanone (1a), a lead compound of site-directed GST-pi inactivator, has been shown to potentiate the cytotoxic effect of cisplatin on tumor cells. As an initial step to develop more potent and more selective haloenol lactone inactivators of GST-pi, we examined the relationship between the chemical structures of haloenol lactone derivatives and their GST inhibitory activity. A total of 16 haloenol lactone derivatives were synthesized to probe the effects of (1) halogen electronegativity, (2) electron density of aromatic rings, (3) molecular size and rigidity, (4) lipophilicity, and (5) aromaticity on the potency of GST-pi inactivation. The inhibitory potency of each compound was determined by time-dependent inhibition tests, and recombinant human GST-pi was used to determine their inhibitory activity. Our structure-activity relationship studies demonstrated that (1) reactivity of the halide leaving group plays a weak role in GST inactivation by the haloenol lactones, (2) aromatic electron density may have some influence on the potency of GST inactivation, (3) high rigidity likely disfavors enzyme inhibition, (4) lipophilicity is inversely proportional to enzyme inactivation, and (5) an unsaturated system may be important for enzyme inhibition. This work facilitated understanding of the interaction of GST-pi with haloenol lactone derivatives as site-directed and isozyme-selective inactivators, possibly potentiating cancer chemotherapy.

  DOI：

  10.1021/jm0499615

文献信息

• A Gallium-Catalyzed Cycloisomerization/Friedel−Crafts Tandem
  作者：Hui-Jing Li、Régis Guillot、Vincent Gandon

  DOI：10.1021/jo101709n

  日期：2010.12.17

  specificity of gallium has been exploited for the synthesis of valuable polycyclic compounds that would be very difficult to prepare otherwise. For instance, tetrahydroisoquinolines and tetrahydrobenzoazepines have been obtained by selective 6-exo-dig or 7-endo-dig cyclization of N-tethered 1,6-arenynes. DFT calculations were carried out to shed light on the mechanism and provide a rationale for this regiodivergency

  在贵金属（Au，Pt，Ru）和第13组（Ga，In）金属催化下，1,6-芳烃重排以高产率，区域控制的方式生成1,2-二氢萘。当反应在富电子芳烃（苯甲醚，苯酚，吲哚衍生物）存在下进行时，可在环异构化步骤之后添加Friedel-Crafts。事实证明只有GaX 3盐能够催化这两个C键形成事件。镓的这种特异性已被用于合成有价值的多环化合物，否则该化合物将很难制备。例如，四氢异喹啉和四氢苯并a庚因已通过选择性6- exo- dig或7- endo获得-N-连接的1，6-芳烃的-dig环化。进行了DFT计算以阐明其机理，并为这种区域差异提供了理论依据。计算还揭示了系链在碳正离子物种稳定中的基本作用。镓和金催化的级联反应中其他类型底物的差异反应性也被暴露出来，表明这两种方法是互补的。特别地，在镓催化下促进了双分子Friedel-Crafts的添加。
• One-Pot Synthesis of Benzene-Fused Medium-Ring Ketones: Gold Catalysis-Enabled Enolate Umpolung Reactivity
  作者：Zhou Xu、Hongyi Chen、Zhixun Wang、Anguo Ying、Liming Zhang

  DOI：10.1021/jacs.6b02533

  日期：2016.5.4

  disclose here that N-alkenoxypyridinium salts, generated readily upon gold-catalyzed additions of protonated pyridine N-oxide to C-C triple bonds of unactivated terminal alkynes, display versatile enolate umpolung chemistry upon heating and react with tethered arene nucleophiles in an SN2' manner. In a synthetically efficient one-pot, two-step process, this chemistry enables expedient preparation of valuable

  与烯醇化物对应物相比，烯醇化物 umpolung 反应性为构建普遍存在的羰基化合物提供了有价值且可能独特的替代方案。我们在此公开了 N-链烯氧基吡啶鎓盐，在金催化下将质子化吡啶 N-氧化物与未活化末端炔烃的 CC 三键加成后很容易生成，在加热时显示出多功能的烯醇化极性化学，并以 SN2' 方式与系链芳烃亲核试剂反应。在合成高效的一锅两步法中，这种化学反应能够方便地从易于获得的芳基取代的线性炔烃中方便地制备有价值的苯并稠合七元/八元环酮，包括 O-/N-杂环酮基材。反应收率可达87%。
• Highly efficient synthesis of functionalized dihydronaphthalenes, tetrahydronaphthalenes, and tetrahydroisoquinolines by iron-catalyzed intramolecular Friedel–Crafts reaction of aryl-containing propargylic alcohols
  作者：Wen Huang、Longcheng Hong、Pengzhi Zheng、Ruiting Liu、Xigeng Zhou

  DOI：10.1016/j.tet.2009.03.007

  日期：2009.5

  An efficient, convenient, and one-pot procedure for the synthesis of a series of new dihydro- and tetrahydronaphthalenes as well as tetrahydroisoquinolines has been established through Lewis acid-catalyzed intramolecular Friedel–Crafts reaction of aryl-substituted propargylic alcohols.

  通过路易斯酸催化的芳基取代的炔丙醇的分子内Friedel-Crafts反应，已经建立了一种高效，方便且一锅的合成一系列新的二氢和四氢萘以及四氢异喹啉的方法。
• Rhodium(III) Porphyrin-catalyzed Reactions via Activation of Alkynes
  作者：Makoto Hasegawa、Takuya Kurahashi、Seijiro Matsubara

  DOI：10.1246/cl.140810

  日期：2014.12.5

  The cycloisomerization of 1,6-enynes catalyzed by rhodium(III) porphyrin under mild reaction conditions successfully afforded a five-membered ring system. The rhodium porphyrin was found to be a strong π-Lewis acid that could activate alkynes. Thus, rhodium porphyrin-catalyzed intramolecular Friedel–Crafts-type reactions of alkynes with arenes were also accomplished. Furthermore, rhodium porphyrin-catalyzed intermolecular cyclization of alkynes with styrenes afforded the indene derivatives.

  在温和反应条件下，由铑(III)卟啉催化的1,6-烯炔的环异构化成功地生成了五元环结构。研究发现，铑卟啉是一种强的π-路易斯酸，能够活化炔烃。因此，铑卟啉催化的炔烃与芳烃的分子内弗里德尔-克拉夫茨类型反应也成功实现。此外，铑卟啉催化的炔烃与苯乙烯的分子间环化反应生成了茚衍生物。
• Ru(II)- and Pt(II)-Catalyzed Cycloisomerization of ω-Aryl-1-alkynes. Generation of Carbocationic Species from Alkynes and Transition Metal Halides and Its Interception by an Aromatic Ring
  作者：Naoto Chatani、Hiroki Inoue、Tsutomu Ikeda、Shinji Murai

  DOI：10.1021/jo000255v

  日期：2000.8.1

  the cyclization mode is dependent on the length of the tethers. The reaction is limited to substrates containing terminal alkynes. A key step of the reaction is the intramolecular interception by an aromatic ring of the vinylmetal complex 2, which contains a cation center at the beta-position, generated from the electrophilic addition of transition metal halides toward an alkyne. The more electron-rich

  用催化量的过渡金属氯化物如PtCl（2）处理芳基-1-炔烃，例如4-芳基-1-丁炔，5-芳基-1-戊炔和6-芳基-1-己炔和[RuCl（2）（CO）（3）]（2），在80°C的甲苯中进行环异构化，生成二氢萘或二氢苯并环庚烯，其中环化方式取决于系链的长度。该反应限于含有末端炔烃的底物。该反应的关键步骤是乙烯基金属配合物2的芳香环在分子内的拦截，该芳香环在β位置包含一个阳离子中心，这是由过渡金属卤化物向炔烃的亲电加成而产生的。较富电子的芳基体系更具反应性。