3-methylene-1,4-diphenylazetidin-2-one | 66977-67-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环丁烷
• 英文名称: 3-methylene-1,4-diphenylazetidin-2-one
• 英文别名: 3-Methylene-1,4-diphenyl-2-azetidinone；3-methylidene-1,4-diphenylazetidin-2-one
• CAS: 66977-67-1
• 化学式: C₁₆H₁₃NO
• 分子量: 235.285
• InChiKey: SFOPBIJMUBHPBA-UHFFFAOYSA-N

物化性质

• 熔点：
  115 °C
• 沸点：
  362.8±42.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4-硝基苯乙烯 、 3-methylene-1,4-diphenylazetidin-2-one 在 Hoveyda-Grubbs catalyst second generation 作用下， 以 甲苯 为溶剂， 反应 40.0h， 以66%的产率得到(Z)-3-(4-Nitrobenzyliden)-1,4-diphenyl-2-azetidinon
  参考文献：
  名称：

  Stereoselective Synthesis of Ezetimibe via Cross-Metathesis of Homoallylalcohols and α-Methylidene-β-Lactams

  摘要：

  Ru-catalyzed cross-metathesis (CM) reaction between beta-arylated alpha-methylidene-beta-lactams and terminal olefins was developed. The CM reaction is effectively catalyzed with Hoveyda-Grubbs second-generation catalyst affording corresponding alpha-alkylidene-beta-aryl-beta-lactams in good isolated yields (41-83%) with exclusive Z-selectivity. The developed protocol was successfully applied for stereoselective preparation of Ezetimibe, the commercial cholesterol absorption inhibitor.

  DOI：

  10.1021/acs.joc.6b01406
• 作为产物：
  描述：

  [(3S,4R)-2-oxo-1,4-diphenylazetidin-3-yl] methanesulfonate 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 生成 3-methylene-1,4-diphenylazetidin-2-one
  参考文献：
  名称：

  对映体的硝酮环转移路线为3-羟基-2-氮杂环丁酮

  摘要：

  4-芳基或杂芳基3-亚甲基β-内酰胺2a–2c与各种硝酮3a–3c进行了高度立体定向的环加成反应。该方法提供了3-羟基-β-内酰胺的对映体特异性途径。©1997由Elsevier Science Ltd发布。

  DOI：

  10.1016/s0040-4039(97)00394-8
• 作为试剂：
  描述：

  4-甲氧基苯乙烯 在 Hoveyda-Grubbs catalyst second generation 、 3-methylene-1,4-diphenylazetidin-2-one 作用下， 反应 40.0h， 生成 4,4'-二甲氧基芪
  参考文献：
  名称：

  Stereoselective Synthesis of Ezetimibe via Cross-Metathesis of Homoallylalcohols and α-Methylidene-β-Lactams

  摘要：

  Ru-catalyzed cross-metathesis (CM) reaction between beta-arylated alpha-methylidene-beta-lactams and terminal olefins was developed. The CM reaction is effectively catalyzed with Hoveyda-Grubbs second-generation catalyst affording corresponding alpha-alkylidene-beta-aryl-beta-lactams in good isolated yields (41-83%) with exclusive Z-selectivity. The developed protocol was successfully applied for stereoselective preparation of Ezetimibe, the commercial cholesterol absorption inhibitor.

  DOI：

  10.1021/acs.joc.6b01406

文献信息

• Synthesis of β-Lactams via Enantioselective Allylation of Anilines with Morita–Baylis–Hillman Carbonates
  作者：You Zi、Markus Lange、Philipp Schüler、Sven Krieck、Matthias Westerhausen、Ivan Vilotijevic

  DOI：10.1055/s-0039-1691570

  日期：2020.4

  Enantioenriched β-lactams are accessed via enantioselective allylation of anilines with Morita–Baylis–Hillman carbonates followed by a base-promoted cyclization. The resulting 3-methyleneazetidin-2-ones are amenable to diastereoselective functionalization to produce analogues of biologically active β-lactams. The use of nearly equimolar quantities of the starting materials make this method efficient and straightforward.

  通过对苯胺进行对映选择性烯丙基化反应制备富含对映体的β-内酰胺，随后通过碱促进的环化反应得到。所得的3-亚甲基氮杂环丙酮可通过对映选择性官能化反应产生生物活性β-内酰胺类似物。该方法使用接近等摩尔量的起始原料使得该方法高效且简单。
• 一种制备螺环β-内酰胺的方法
  申请人：合肥工业大学

  公开号：CN111333560A

  公开（公告）日：2020-06-26

  本发明公开了一种制备螺环β‑内酰胺的方法，其包括如下步骤：β‑内酰胺与酮酸酯在膦类催化剂条件下发生[2+1]环化反应生成螺环β‑内酰胺。本发明所述方法是一种不涉及金属催化合成螺环β‑内酰胺的途径。该制备螺环β‑内酰胺的方法条件温和、反应迅速，所用原料廉价易得、操作简单，能够快速获得含有不同取代基的螺环β‑内酰胺结构。
• P(NMe₂)₃ mediated cyclopropanation of α-methylene-β-lactams for rapid syntheses of spirocyclopropyl β-lactams
  作者：Si-Qin Luo、Wei Liu、Ban-Feng Ruan、Shi-Lu Fan、Hui-Xia Zhu、Wei Tao、Hua Xiao

  DOI：10.1039/d0ob00826e

  日期：——

  An expedient cyclopropanation of α-methylene-β-lactams with α-ketoesters mediated by P(NMe2)3 has been developed. This reaction enables rapid access to a series of functionalized spirocyclopropyl β-lactams in good yields from bench-stable starting materials under mild conditions. The experimental results indicated that the C3-substituent of the α-methylene-β-lactam not only significantly impacted the

  已经开发了由P（NMe 2）3介导的具有α-酮酸酯的方便的α-亚甲基-β-内酰胺的环丙烷化反应。该反应使得可以在温和条件下从稳定的起始原料以高收率快速获得一系列官能化的螺环丙基β-内酰胺。实验结果表明，α-亚甲基-β-内酰胺的C3取代基不仅显着影响反应效率和立体化学，而且在确定反应的化学选择性方面起着关键作用。
• A Simple and Direct Synthesis of 3-Methylene-1, 4-diarylazetidin-2-ones and (E)-3-Arylidene-1-phenylazetidin-2-ones Using Baylis–Hillman Derivatives
  作者：Manickam Bakthadoss、Jayakumar Srinivasan、Raman Selvakumar

  DOI：10.1071/ch13382

  日期：——

  Herein we describe a direct method, promoted by potassium tert-butoxide (KOtBu), for the synthesis of highly substituted α-methylene β-lactams and α-arylidene β-lactams from the amino ester intermediates derived from the acetates and bromo derivatives of the Baylis–Hillman adducts. A variety of β-lactams was synthesized in a single step with good yields.

  在此，我们介绍了一种在叔丁醇钾（KOtBu）促进下直接合成高取代的 α-亚甲基 β-内酰胺和 α-亚芳基 β-内酰胺的方法，其氨基酯中间体来自 Baylis-Hillman 加合物的乙酸盐和溴衍生物。各种 β-内酰胺都是一步合成的，而且收率很高。
• Synthesis of β-Amino Esters by Regioselective Amination of Allyl Bromides with Aryl and Alkyl Amines
  作者：Chun-Cheng Lin、Adam Shih-Yuan Lee、Hung-Yang Chen、Laxmikant N. Patkar、Shau-Hua Ueng

  DOI：10.1055/s-2005-871934

  日期：——

  One of the two possible regioisomers can be exclusively formed by combining a suitable solvent and a specific amount of triethylamine as a base during the amination of allyl bromide 5. The SN2′ product 7 was produced using dichloromethane as a solvent and triethylamine (7 equiv) as base; SN2 product 6 was predominantly generated in hexane with 0.5 equivalents of triethylamine. Furthermore, a new reaction condition for the efficient cyclization of 7 to yield α-methylene β-lactam 8 using Sn[N(TMS)2]2 as a ­reagent, is disclosed.

  在烯丙基溴 5 的胺化过程中，通过将合适的溶剂和特定量的三乙胺作为碱混合，可以专门形成两种可能的区域异构体之一。使用二氯甲烷作为溶剂和三乙胺（7 当量）生产 SN2' 产物 7。作为基础； SN2产物6主要在己烷和0.5当量三乙胺中产生。此外，还公开了使用 Sn[N(TMS)2]2 作为试剂，有效环化 7 生成 α-亚甲基 β-内酰胺 8 的新反应条件。