ethyl 3-amino-3-(2-naphthyl)propenoate

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: ethyl 3-amino-3-(2-naphthyl)propenoate
• 英文别名: ethyl 3-amino-3-(naphthalen-2-yl)acrylate；3-(1-naphthyl)-3-amino ethyl acrylate；Ethyl 3-amino-3-naphthalen-2-ylprop-2-enoate；ethyl 3-amino-3-naphthalen-2-ylprop-2-enoate
• 化学式: C₁₅H₁₅NO₂
• 分子量: 241.29
• InChiKey: MPXDBUBDUAISFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(3-苯基丙-2-炔-1-亚基)戊烷-2,4-二酮 、 ethyl 3-amino-3-(2-naphthyl)propenoate 在 silver tetrafluoroborate 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以71%的产率得到4-(4-acetyl-5-methylfuran-2-yl)-5-(naphthalen-2-yl)-4-phenyl-3,4-dihydro-2H-pyrrol-2-one
  参考文献：
  名称：

  银（I）催化的多米诺烯与烯胺的环化/环丙烷化/环裂解/亲核取代反应：4-（呋喃-2-基）-3,4-二氢-2H-吡咯-2-酮的合成。

  摘要：

  我们报告了4-（呋喃-2-基）-3,4-二氢-2 H-吡咯-2-酮衍生物的合成。通过这种方法，通过银（I）催化的烯酮级联环化/环丙烷化/环裂解/亲核取代反应构建了呋喃环和3,4-二氢-2 H-吡咯-2-酮两个核心结构。与烯胺。已经提出了合理的机制。该方法具有化学选择性高，反应条件温和，操作简单，反应时间短等优点。

  DOI：

  10.1021/acs.joc.0c01711
• 作为产物：
  描述：

  3-萘-3-氧丙酸乙酯 在 乙醇 、 ammonium acetate 作用下， 生成 ethyl 3-amino-3-(2-naphthyl)propenoate
  参考文献：
  名称：

  Transition metal-free [3 + 3] annulation of cyclopropanols with β-enamine esters to assemble nicotinate derivatives

  摘要：

  开发了一种原子经济合成方法，可在无金属和添加剂条件下制备结构重要的烟酸盐。

  DOI：

  10.1039/d3ob01662e

文献信息

• Chiral Lewis Base-Catalyzed, Enantioselective Reduction of Unprotected β-Enamino Esters with Trichlorosilane
  作者：Jianheng Ye、Chao Wang、Lin Chen、Xinjun Wu、Li Zhou、Jian Sun

  DOI：10.1002/adsc.201501061

  日期：2016.3.31

  reduction of N‐unsubstituted β‐enamino esters represents a major challenge for asymmetric catalysis. In this paper, the first organocatalytic system that could be used for the asymmetric hydrosilylation of N‐unsubstituted β‐enamino esters has been developed. Using N‐tert‐butylsulfinyl‐L‐proline‐derived amides and L‐pipecolinic acid‐derived formamides as catalyst, a broad range of β‐aryl‐ and β‐alkyl‐substituted

  N-未取代的β-烯胺酯的催化不对称还原是不对称催化的主要挑战。在本文中，开发了第一个可用于N-未取代的β-烯氨基酯不对称氢化硅烷化的有机催化体系。使用ñ -叔-butylsulfinyl-大号脯氨酸衍生的酰胺和大号-pipecolinic酸衍生甲酰胺作为催化剂，广泛β -芳基-和β-烷基取代的游离β氨基酯可以以高产率制备，并且对映选择性。（R）-3-氨基-3-苯基丙酸乙酯和异丙基（S）-3-氨基-4-（2,3,5-三氟苯基）丁酸酯。所得产品可以通过短合成途径顺利转化为FDA批准的药物达泊西汀和西他列汀。
• Controlling the rates of reductively-activated elimination from the (indol-3-yl)methyl position of indolequinones
  作者：Steven A. Everett、Matthew A. Naylor、Paola Barraja、Elizabeth Swann、Kantilal B. Patel、Michael R. L. Stratford、Anna R. Hudnott、Borivoj Vojnovic、Rosalind J. Locke、Peter Wardman、Christopher J. Moody

  DOI：10.1039/b009652k

  日期：——

  A series of substituted 3-(4-nitrophenyloxy)methylindole-4,7-diones (Q) were synthesised. The effects of substitution patterns on the indole core on rates of elimination of 4-nitrophenol as a model for drug release following fragmentation of a phenolic ether linker were studied. After reduction to either the radical anion (Q˙−) or hydroquinone (QH2) elimination of 4-nitrophenol occurred from the (indol-3-yl)methyl position. The half-lives of Q˙− radicals at [O2] ≈ 5 µmol dm−3, typical of tumour hypoxia, were t½ ≈ 0.3–1.8 ms, the higher values associated with higher reduction potentials. Half-lives for the autoxidation of the QH2 were markedly longer at the same oxygen concentration (t½ ≈ 8–102 min) and longer still in the presence of 4 µmol dm−3 superoxide dismutase (t½ ≈ 8–19 h). Although the indolequinones were able to eliminate 4-nitrophenol with high efficiency only Q˙− radicals of the 3-carbinyl substituted derivatives did so with sufficiently short half-lives (t½ ≈ 41–2 ms) to compete with electron transfer to oxygen and therefore have the potential to target the leaving group to hypoxic tissue. The hydroquinones are not sufficiently oxygen sensitive to prevent the elimination of 4-nitrophenol (t½ ≈ 1.5–3.5 s) even at oxygen concentrations expected in normal tissue. By incorporating electron rich substituents at the indolyl carbinyl position it is possible to control the rate of reductive fragmentation. This may prove an important factor in the design of an indolequinone-based bioreductive drug delivery system.

  合成了一系列取代的3-(4-硝基苯氧基)甲基吲哚-4,7-二酮（Q）。研究了取代模式对吲哚核心在4-硝基苯酚释放速率上的影响，作为药物释放的模型，药物释放是通过酚醚连接链的断裂发生的。在还原为自由基阴离子（Q˙−）或氢醌（QH2）后，4-硝基苯酚从（吲哚-3-基）甲基位置释放。Q˙−自由基在[O2] ≈ 5 µmol dm−3（典型的肿瘤缺氧环境）下的半衰期为t½ ≈ 0.3–1.8毫秒，较高的半衰期值与较高的还原电位相关。在相同的氧浓度下，QH2的自氧化半衰期明显更长（t½ ≈ 8–102分钟），在存在4 µmol dm−3超氧化物歧化酶的情况下更长（t½ ≈ 8–19小时）。尽管吲哚醌能够以高效率释放4-硝基苯酚，但仅有3-羧基取代的Q˙−自由基具有足够短的半衰期（t½ ≈ 41–2毫秒）以与氧的电子转移竞争，因此具有将离去基团靶向缺氧组织的潜力。即使在正常组织中预期的氧浓度下，氢醌的氧敏感性不足以阻止4-硝基苯酚的释放（t½ ≈ 1.5–3.5秒）。通过在吲哚基甲基位置引入富电子取代基，可以控制还原性碎裂的速率。这可能成为设计基于吲哚醌的生物还原药物递送系统的重要因素。
• Isothiourea and Brønsted Acid Cooperative Catalysis: Enantioselective Construction of Dihydropyridinones
  作者：Yu-Chen Zhang、Rui-Long Geng、Jin Song、Liu-Zhu Gong

  DOI：10.1021/acs.orglett.0c00461

  日期：2020.3.20

  Asymmetric annulation of bench-stable α,β-unsaturated aryl esters with enamines was realized via cooperative catalysis of chiral isothiourea and Brønsted acid. This reaction proceeds via a chiral α,β-unsaturated acyl ammonium intermediate and offers a rapid access to functionalized 3,4-dihydropyridin-2-ones in high yields and excellent enantioselectivities.

  通过手性异硫脲和布朗斯台德酸的协同催化，可实现替宁稳定的α，β-不饱和芳基酯与烯胺的不对称环化。该反应通过手性α，β-不饱和酰基铵中间体进行，并以高收率和优异的对映选择性快速获得官能化的3，4-二氢吡啶-2-酮。
• Copper-Catalyzed Tandem Reaction of Enamino Esters with <i>ortho</i> -Halogenated Aromatic Carbonyls: One-Pot Approach to Functionalized Quinolines
  作者：Fei Peng、Jin Liu、Lili Li、Zhiwei Chen

  DOI：10.1002/ejoc.201701472

  日期：2018.2.7

  tandem reaction was developed for the efficient synthesis of functionalized quinolones. The C–C bond formation and C–N coupling reaction of enamino esters and ortho‐halogenated aromatic carbonyl compounds gave products in moderate to good yields. A successful gram‐scale protocol and synthesis of a thieno[3,2‐b]pyridine derivative show further applications of this approach.

  为了有效合成功能化喹诺酮，开发了铜催化串联反应。烯氨基酯与邻卤代芳族羰基化合物的C–C键形成和C–N偶联反应使产物收率适中至良好。成功的克级规程和噻吩并[3,2- b ]吡啶衍生物的合成表明了该方法的进一步应用。
• Synthesis of multi-arylated pyridines via tandem oxidative reaction
  作者：Dongping Cheng、Hongjiao Yang、Chenze Yu、Yuhui Tao、Xiaoliang Xu

  DOI：10.1016/j.tetlet.2022.154243

  日期：2022.12

  An efficient tandem reaction of β-enaminoesters and 1,3-diarylpropenes is disclosed. It undergoes oxidative coupling mediated by DDQ, subsequent intermolecular cyclization and dehydro-aromatization catalyzed by Cu/TBHP in the presence of O2. A series of multi-arylated pyridines is obtained in moderate to excellent yields.

  公开了 β-烯胺酯和 1,3-二芳基丙烯的有效串联反应。它经历由DDQ介导的氧化偶联，随后在O 2存在下由Cu/TBHP催化的分子间环化和脱氢芳构化。以中等到极好的收率获得了一系列多芳基化的吡啶。