methyl 4-hydroxy-2-methylene-4-phenylbutanoate | 138832-36-7

• 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: methyl 4-hydroxy-2-methylene-4-phenylbutanoate
• 英文别名: Methyl 4-hydroxy-2-methylidene-4-phenylbutanoate
• CAS: 138832-36-7
• 化学式: C₁₂H₁₄O₃
• 分子量: 206.241
• InChiKey: CNSZHCJOKDGJQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 4-hydroxy-2-methylene-4-phenylbutanoate 在 对甲苯磺酸 作用下， 以 乙二醇二甲醚 为溶剂， 反应 2.0h， 以98%的产率得到3-methylene-4-phenyldihydrofuran-2(3H)-one
  参考文献：
  名称：

  Metal-Mediated Reactions of α-Bromomethyl-Propenoate Esters

  摘要：

  Methyl-2-bromomethylprop-2-enoate reacts with benzaldehyde and with salicylaldehyde via its Sn and Zn complexes under aqueous conditions to form alpha-methylene-gamma-lactones in high yields. In the case of salicylaldehyde X-ray analysis proves conclusively formation of a five- rather than a seven-membered ring. Under the above conditions 2-bromomethyl-3-phenylprop-2-enoate does not afford any cyclic products.

  DOI：

  10.1080/00397919508011363
• 作为产物：
  描述：

  2-(羟甲基)丙烯酸甲酯 在 呋喃 、 indium 、 氢溴酸 、 溶剂黄146 作用下， 以 水 为溶剂， 生成 methyl 4-hydroxy-2-methylene-4-phenylbutanoate
  参考文献：
  名称：

  Diastereoselective synthesis of α-(aminomethyl)-γ-butyrolactones via a catalyst-free aminolactonization

  摘要：

  一种涉及aza-Michael反应、质子转移和内酯化的自催化多米诺反应，以近定量的收率和优秀的对映选择性提供了α-氨基甲基-γ-丁内酯。

  DOI：

  10.1039/c4cc05765a

文献信息

• Organometallic reactions in aqueous media with indium
  作者：C.J. Li、T.H. Chan

  DOI：10.1016/0040-4039(91)85028-4

  日期：1991.11

  Allylation reactions of aldehydes and ketones occurred smoothly with indium metal in aqueous media. Compared to similar reactions with zinc and tin, the reaction with indium proceeds without the need of any promoter. The reaction can be extended to the synthesis of 2-methylene-γ-lactone 6 via the condensation of carbonyl compounds with 2-bromomethylacrylate 4.

  醛和酮的烯丙基化反应与铟金属在水性介质中的反应平稳进行。与与锌和锡的类似反应相比，与铟的反应无需任何促进剂即可进行。该反应可扩展到2-亚甲基γ内酯的合成6通过羰基化合物的缩合与2- bromomethylacrylate 4。
• Isatin Derived Spirocyclic Analogues with α-Methylene-γ-butyrolactone as Anticancer Agents: A Structure–Activity Relationship Study
  作者：Sandeep Rana、Elizabeth C. Blowers、Calvin Tebbe、Jacob I. Contreras、Prakash Radhakrishnan、Smitha Kizhake、Tian Zhou、Rajkumar N. Rajule、Jamie L. Arnst、Adnan R. Munkarah、Ramandeep Rattan、Amarnath Natarajan

  DOI：10.1021/acs.jmedchem.6b00400

  日期：2016.5.26

  Design, synthesis, and evaluation of α-methylene-γ-butyrolactone analogues and their evaluation as anticancer agents is described. SAR identified a spirocyclic analogue 19 that inhibited TNFα-induced NF-κB activity, cancer cell growth and tumor growth in an ovarian cancer model. A second iteration of synthesis and screening identified 29 which inhibited cancer cell growth with low-μM potency. Our data

  描述了α-亚甲基-γ-丁内酯类似物的设计，合成和评估及其作为抗癌剂的评估。SAR鉴定出在卵巢癌模型中可抑制TNFα诱导的NF-κB活性，癌细胞生长和肿瘤生长的螺环类似物19。合成和筛选的第二次迭代确定了29个以低μM效能抑制癌细胞生长的物质。我们的数据表明，从伊斯兰衍生的螺环α-亚甲基-γ-丁内酯是用于优化识别新型抗癌药的合适核心。
• Indium mediated allylation and propargylation reactions of dimethyl acetals and ketals
  作者：Jin Sun Kwon、Ae Nim Pae、Kyung Il Choi、Hun Yeong Koh、Youseung Kim、Yong Seo Cho

  DOI：10.1016/s0040-4039(01)00042-9

  日期：2001.3

  Indium mediated allylation and propargylation reactions of acetals and ketals with various allyl or propargyl bromides in aqueous media successfully provided the corresponding homoallylic or homopropargylic (and allenylic) alcohol, respectively, in moderate to good yields. Highly chemoselective allylation is also described. The ketal and aryl acetal could be selectively allylated over the aliphatic

  缩醛和缩酮与各种烯丙基或炔丙基溴在水介质中的铟介导的烯丙基化和炔丙基化反应分别以中等至良好的收率成功提供了相应的均烯丙基或均炔丙基（和烯丙基）醇。还描述了高度化学选择性的烯丙基化。缩酮和芳基缩醛可以选择性地烯丙基化在脂肪族缩醛上，收率为80-84％。
• Rhodium-Catalyzed Enantioconvergent Isomerization of Homoallylic and Bishomoallylic Secondary Alcohols
  作者：Rui-Zhi Huang、Kai Kiat Lau、Zhaofeng Li、Tang-Lin Liu、Yu Zhao

  DOI：10.1021/jacs.8b07007

  日期：2018.11.7

  (up to 95%, 86% ee) but also a concomitant oxidative kinetic resolution of the alcohol substrates (S > 20). In the case of bishomoallylic alcohols, an intriguing ligand-induced divergent reactivity was observed. A terminal-to-internal alkene isomerization promoted by Rh/L7 followed by redox isomerization using Rh/BINAP system produced chiral ketones bearing a γ-stereocenter with high yield and enantioselectivity

  我们在此提出了一种前所未有的均烯丙基和双烯丙基仲醇的对映选择性异构化，由市售的铑配合物和碱催化。这种催化氧化还原中性过程以高效率和对映选择性有效获取手性酮，而无需使用任何化学计量试剂或产生任何废物。对于高烯丙醇的反应，该系统不仅实现了对带有 β 立体中心的手性酮的立体聚合（高达 95%，86% ee），而且还实现了醇底物的伴随氧化动力学分辨率（S > 20）。在双烯丙醇的情况下，观察到了有趣的配体诱导的发散反应性。由 Rh/L7 促进的末端到内部烯烃异构化，然后使用 Rh/BINAP 系统氧化还原异构化产生了带有 γ-立体中心的手性酮，具有高产率和对映选择性。机理研究为具有关键烷基-Rh 中间体链行走的氧化还原异构化途径提供了强有力的支持。
• Highly Diastereoselective Hydrostannylation of Allyl and Homoallyl Alcohols with Dibutyl(trifluoromethanesulfoxy)stannane
  作者：Katsukiyo Miura、Di Wang、Akira Hosomi

  DOI：10.1021/ja052245n

  日期：2005.7.1

  Dibutyl(trifluoromethanesulfoxy)stannane (Bu2Sn(OTf)H, 1a) was found to be very valuable for highly diastereoselective homolytic hydrostannylation of allyl and homoallyl alcohols. alpha,beta-Disubstituted allyl alcohols and alpha,gamma-disubstituted homoallyl alcohols were converted into gamma- and delta-stannylated alcohols with high 1,2-syn and 1,3-syn diastereoselectivity, respectively. The origin of the stereochemical outcomes can be rationalized by conformational fixation of the intermediary beta-stannylalkyl radical by coordination of the hydroxy group to the Lewis acidic tin center.