ethyl 5-bromo-5-phenylpentanoate | 874656-04-9

• 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: ethyl 5-bromo-5-phenylpentanoate
• CAS: 874656-04-9
• 化学式: C₁₃H₁₇BrO₂
• 分子量: 285.181
• InChiKey: IVHZVULPZJUUJC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  ethyl 5-bromo-5-phenylpentanoate 在 potassium carbonate 、 potassium iodide 、 三氯氧磷 作用下， 以 甲苯 、 正丁醇 为溶剂， 反应 73.0h， 生成 4-Phenyl-1,2,3,4,6,7,12,12b-octahydro-indolo[2,3-a]quinolizine
  参考文献：
  名称：

  Dopamine/Serotonin Receptor Ligands. 10: SAR Studies on Azecine-type Dopamine Receptor Ligands by Functional Screening at Human Cloned D₁, D_2L, and D₅ Receptors with a Microplate Reader Based Calcium Assay Lead to a Novel Potent D₁/D₅ Selective Antagonist

  摘要：

  On the basis of the benz[d]indolo[2,3-g]azecine derivative I (LE300), structure-activity relations were investigated in order to identify the pharmacophore in this new class of ligands. Various structural modifications were performed and the inhibitory activities at human cloned D-1, D-2L, and D-5 receptors were measured by using a simple fluorescence microplate reader based calcium assay. Subsequently, the affinities of active compounds were estimated by radioligand binding experiments. Deleting one of the aromatic rings as well as replacing it by a phenyl moiety abolishes the inhibitory activities almost completely. Contraction of the 10-membered central ring decreases them significantly. The replacement of indole by thiophene or N-methylpyrrole reduces the inhibitory activity, whereas replacing the indole by benzene increases it. Finally, the hydroxylated dibenz[d,g]azecine derivative 11d (LE404) was found to be more active than the lead I in the functional calcium assay as well as in radioligand displacement experiments.

  DOI：

  10.1021/jm050846j
• 作为产物：
  描述：

  4-苯甲酰基丁酸 在 sodium hydroxide 、 sodium tetrahydroborate 、 氢溴酸 作用下， 反应 17.0h， 生成 ethyl 5-bromo-5-phenylpentanoate
  参考文献：
  名称：

  Dopamine/Serotonin Receptor Ligands. 10: SAR Studies on Azecine-type Dopamine Receptor Ligands by Functional Screening at Human Cloned D₁, D_2L, and D₅ Receptors with a Microplate Reader Based Calcium Assay Lead to a Novel Potent D₁/D₅ Selective Antagonist

  摘要：

  On the basis of the benz[d]indolo[2,3-g]azecine derivative I (LE300), structure-activity relations were investigated in order to identify the pharmacophore in this new class of ligands. Various structural modifications were performed and the inhibitory activities at human cloned D-1, D-2L, and D-5 receptors were measured by using a simple fluorescence microplate reader based calcium assay. Subsequently, the affinities of active compounds were estimated by radioligand binding experiments. Deleting one of the aromatic rings as well as replacing it by a phenyl moiety abolishes the inhibitory activities almost completely. Contraction of the 10-membered central ring decreases them significantly. The replacement of indole by thiophene or N-methylpyrrole reduces the inhibitory activity, whereas replacing the indole by benzene increases it. Finally, the hydroxylated dibenz[d,g]azecine derivative 11d (LE404) was found to be more active than the lead I in the functional calcium assay as well as in radioligand displacement experiments.

  DOI：

  10.1021/jm050846j

文献信息

• Enantioconvergent Cu-Catalyzed Radical C–N Coupling of Racemic Secondary Alkyl Halides to Access α-Chiral Primary Amines
  作者：Yu-Feng Zhang、Xiao-Yang Dong、Jiang-Tao Cheng、Ning-Yuan Yang、Li-Lei Wang、Fu-Li Wang、Cheng Luan、Juan Liu、Zhong-Liang Li、Qiang-Shuai Gu、Xin-Yuan Liu

  DOI：10.1021/jacs.1c07726

  日期：2021.9.22

  α-Chiral alkyl primary amines are virtually universal synthetic precursors for all other α-chiral N-containing compounds ubiquitous in biological, pharmaceutical, and material sciences. The enantioselective amination of common alkyl halides with ammonia is appealing for potential rapid access to α-chiral primary amines, but has hitherto remained rare due to the multifaceted difficulties in using ammonia

  α-手性烷基伯胺实际上是生物、制药和材料科学中普遍存在的所有其他α-手性含氮化合物的通用合成前体。普通烷基卤与氨的对映选择性胺化对于快速获得 α-手性伯胺很有吸引力，但由于使用氨的多方面困难和不发达的 C(sp 3 )-N 偶联，迄今为止仍然很少见。在这里，我们展示了亚砜亚胺作为优异的氨替代物，用于在温和的热条件下通过铜催化与不同的外消旋仲烷基卤化物（> 60 个例子）对映聚合自由基 C-N 偶联。该反应有效地提供了高度对映体富集的N-烷基亚砜亚胺（产率高达 99% 和 >99% ee），具有仲苄基、炔丙基、α-羰基烷基和 α-氰基烷基立体中心。此外，我们已将由此获得的掩蔽 α-手性伯胺转化为各种合成结构单元、配体和具有 α-手性 N-官能团的药物，如氨基甲酸酯、羧酰胺、仲和叔胺和恶唑啉，常见的α-取代模式。这些结果揭示了对映会聚自由基交叉偶联作为一般手性碳-杂原子形成策略的潜力。
• A general asymmetric copper-catalysed Sonogashira C(sp3)–C(sp) coupling
  作者：Xiao-Yang Dong、Yu-Feng Zhang、Can-Liang Ma、Qiang-Shuai Gu、Fu-Li Wang、Zhong-Liang Li、Sheng-Peng Jiang、Xin-Yuan Liu

  DOI：10.1038/s41557-019-0346-2

  日期：2019.12

  versatile reaction for the straightforward formation of C–C bonds, forging the carbon skeletons of broadly useful functionalized molecules. However, asymmetric Sonogashira coupling, particularly for C(sp3)–C(sp) bond formation, has remained largely unexplored. Here we demonstrate a general stereoconvergent Sonogashira C(sp3)–C(sp) cross-coupling of a broad range of terminal alkynes and racemic alkyl halides

  Sonogashira偶联的不断发展使它成为直接建立C–C键的公认且通用的反应，从而锻造了广泛有用的功能化分子的碳骨架。但是，特别是对于C（sp 3）–C（sp）键形成的非对称Sonogashira偶联，在很大程度上仍未得到开发。在这里，我们展示了一个一般的立体会聚Sonogashira C（sp 3）–C（sp）使用手性金鸡纳生物碱基的P，N-配体，通过铜催化的自由基参与的炔基化作用实现了广泛的末端炔烃和外消旋烷基卤化物（> 120实例）的交叉偶联。与工业相关的乙炔和丙炔已成功整合，为可扩展且经济的合成应用奠定了基础。该方法的潜在用途在具有丰富手性C（sp 3）–C（sp / sp 2 / sp 3）特征的立体富集的生物活性或功能分子衍生物，药物化合物和天然产物的简便合成中得到了证明。）债券。这项工作强调了自由基物种对发展对映会聚转化的重要性。
• Copper-Catalyzed Enantioconvergent Radical Suzuki–Miyaura C(sp³)–C(sp²) Cross-Coupling
  作者：Sheng-Peng Jiang、Xiao-Yang Dong、Qiang-Shuai Gu、Liu Ye、Zhong-Liang Li、Xin-Yuan Liu

  DOI：10.1021/jacs.0c09125

  日期：2020.11.18

  A copper-catalyzed enantioconvergent Suzuki-Miyaura C(sp3)-C(sp2) cross-coupling of various racemic alkyl halides with organoboronate esters has been established in high enantioselectivity. Critical to the success is the use of a chiral cinchona alkaloid-derived N,N,P-ligand for not only enhancing the reducing capability of copper catalyst to favor a stereoablative radical pathway over a stereospecific

  各种外消旋卤代烷与有机硼酸酯的铜催化对映收敛 Suzuki-Miyaura C(sp3)-C(sp2) 交叉偶联已经建立，具有高对映选择性。成功的关键是使用手性金鸡纳生物碱衍生的 N,N,P-配体，不仅提高铜催化剂的还原能力，有利于立体定向 SN2 型过程的立体消除自由基途径，而且提供理想的手性环境以实现对高活性自由基物种的具有挑战性的对映控制。该反应在偶联伙伴方面具有广泛的范围，包括芳基-和杂芳基硼酸酯，以及具有良好官能团兼容性的苄基-、杂苄基-和炔丙基溴化物和氯化物。因此，
• Design of Hemilabile N,N,N-Ligands in Copper-Catalyzed Enantioconvergent Radical Cross-Coupling of Benzyl/Propargyl Halides with Alkenylboronate Esters
  作者：Peng-Fei Wang、Jiao Yu、Kai-Xin Guo、Sheng-Peng Jiang、Ji-Jun Chen、Qiang-Shuai Gu、Ji-Ren Liu、Xin Hong、Zhong-Liang Li、Xin-Yuan Liu

  DOI：10.1021/jacs.2c00957

  日期：2022.4.13

  halides with alkenylboronate esters is an appealing tool in the assembly of synthetically valuable enantioenriched alkenes owing to the ready availability, low toxicity, and air/moisture stability of alkenylboronate esters. Here, we report a copper/chiral N,N,N-ligand catalytic system for the enantioconvergent cross-coupling of benzyl/propargyl halides with alkenylboronate esters (>80 examples) with good

  对映收敛基团 C(sp 3 )–C(sp 2) 烷基卤化物与烯基硼酸酯的交叉偶联是合成有价值的对映体富集烯烃的一种有吸引力的工具，因为烯基硼酸酯易于获得、低毒性和空气/水分稳定性。在这里，我们报告了一种铜/手性 N,N,N-配体催化体系，用于苄基/炔丙基卤化物与烯基硼酸酯（>80 个实例）的对映收敛交叉偶联，具有良好的官能团耐受性。成功的关键是通过在一个配位喹啉环的邻位安装空间位阻来合理设计半可溶性N,N,N-配体。因此，新设计的配体不仅可以促进三齿形式的自由基交叉偶联过程，还可以对二齿形式的高反应性烷基自由基进行对映控制。
• A general copper-catalysed enantioconvergent C(sp3)–S cross-coupling via biomimetic radical homolytic substitution
  作者：Yu Tian、Xi-Tao Li、Ji-Ren Liu、Jian Cheng、Ang Gao、Ning-Yuan Yang、Zhuang Li、Kai-Xin Guo、Wei Zhang、Han-Tao Wen、Zhong-Liang Li、Qiang-Shuai Gu、Xin Hong、Xin-Yuan Liu

  DOI：10.1038/s41557-023-01385-w

  日期：2024.3

  Although α-chiral C(sp3)–S bonds are of enormous importance in organic synthesis and related areas, the transition-metal-catalysed enantioselective C(sp3)–S bond construction still represents an underdeveloped domain probably due to the difficult heterolytic metal–sulfur bond cleavage and notorious catalyst-poisoning capability of sulfur nucleophiles. Here we demonstrate the use of chiral tridentate

  尽管α-手性C( sp 3 )–S键在有机合成及相关领域中具有极其重要的意义，但过渡金属催化的对映选择性C( sp 3 )–S键结构仍然代表着一个不发达的领域，这可能是由于困难的异质分解造成的。金属-硫键断裂和硫亲核试剂臭名昭著的催化剂中毒能力。在这里，我们演示了使用手性三齿阴离子配体与 Cu(I) 催化剂相结合，使外消旋仲卤代烷和叔卤代烷与高度可转化的硫亲核试剂发生仿生对映自由基 C( sp 3 )-S 交叉偶联反应。该方案不仅具有广泛的底物范围和高对映选择性，而且还提供了一系列具有不同硫氧化态的有用的α-手性烷基有机硫化合物的通用途径，从而为已知的不对称C( sp 3 )–S键提供了补充方法形成方法。机理结果支持关键的 C( sp 3 )-S 键形成步骤的仿生自由基均裂取代途径。