1-bromo-2-methoxy-6-phenylnaphthalene | 1262388-36-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-bromo-2-methoxy-6-phenylnaphthalene
• 英文别名: 1-bromo-2-methoxy-6-phenylnaphtalene
• CAS: 1262388-36-2
• 化学式: C₁₇H₁₃BrO
• 分子量: 313.194
• InChiKey: OPYAJWAXXUHLPI-UHFFFAOYSA-N

物化性质

• 沸点：
  428.6±30.0 °C(Predicted)
• 密度：
  1.367±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  19
• 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：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-bromo-2-methoxy-6-phenylnaphthalene 在 palladium diacetate 、 三溴化硼 、 potassium carbonate 、 三苯基膦 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 为溶剂， -78.0~150.0 ℃ 、1.5 MPa 条件下， 反应 1.25h， 生成 6-phenyl-1-(pyrimidin-5-yl)-2-naphthol
  参考文献：
  名称：

  New Drug-Like Hydroxyphenylnaphthol Steroidomimetics As Potent and Selective 17β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors for the Treatment of Estrogen-Dependent Diseases

  摘要：

  Inhibition of 17 beta-hydroxysteroid dehydrogenase type 1 (17 beta-HSD1) is a novel and attractive approach to reduce the local levels of the active estrogen 17 beta-estradiol in patients with estrogen-dependent diseases like breast cancer or endometriosis. With the aim of optimizing the biological profile of 17 beta-HSD1 inhibitors from the hydroxyphenylnaphthol class, structural optimizations were performed at the 1-position of the naphthalene by introduction of different heteroaromatic rings as well as substituted phenyl groups. In the latter class of compounds, which were synthesized applying Suzuki-cross coupling, the 3-methane-sulfonamide 15 turned out to be a highly potent 17 beta-HSD1 inhibitor (IC50 = 15 nM in a cell-free assay). It was also very active in the cellular assay (T47D cells, IC50 = 71 nM) and selective toward 17 beta-HSD2 and the estrogen receptors alpha and beta. It showed a good membrane permeation and metabolic stability and was orally available in the rat.

  DOI：

  10.1021/jm1009082
• 作为产物：
  描述：

  6-phenyl-2-naphthol 在 N-溴代丁二酰亚胺(NBS) 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 12.0h， 生成 1-bromo-2-methoxy-6-phenylnaphthalene
  参考文献：
  名称：

  钯催化的2-芳基环己烯-2-烯酮阻转异构体的对映选择性合成：用于轴向合成手性联芳基化合物的平台分子

  摘要：

  据报道，钯催化从2-碘-3-甲基环己-2-烯酮和芳基硼酸不对称合成基于烯酮的阻转异构体。BoPhoz型膦-氨基膦配体表现出优于其他配体的对映选择性。这些基于环己烯酮的阻转异构体是用于进一步完善的有用化合物。证明了具有不同邻取代基的联芳基阻转异构体的发散合成。

  DOI：

  10.1002/anie.201701467

文献信息

• Construction of Axially Chiral Arylborons via Atroposelective Miyaura Borylation
  作者：Kai Yang、Yanfei Mao、Jie Xu、Hao Wang、Yong He、Wangyang Li、Qiuling Song

  DOI：10.1021/jacs.1c04345

  日期：2021.7.14

  well-developed centrally chiral boron chemistry, C–B axially chiral chemistry remains elusive and challenging. Herein we report the first atroposelective Miyaura borylation of bromoarenes with unsymmetrical diboron reagents for the direct catalytic synthesis of optically active atropisomeric arylborons. This reaction features broad substrate scope and produces axially chiral arylborons with high yields

  与发达的中心手性硼化学相比，C-B 轴向手性化学仍然难以捉摸和具有挑战性。在此，我们报告了第一次使用不对称二硼试剂对溴芳烃进行阻转选择性 Miyaura 硼酸化，用于直接催化合成旋光阻转异构芳基硼。该反应具有广泛的底物范围，可产生高产率和良好对映选择性的轴向手性芳基硼。
• Catalytic Asymmetric Construction of Axially and Centrally Chiral Heterobiaryls by Minisci Reaction
  作者：Dong Liang、Jia-Rong Chen、Li-Ping Tan、Zi-Wei He、Wen-Jing Xiao

  DOI：10.1021/jacs.2c01116

  日期：2022.4.6

  efficient synthesis of axially chiral heterobiaryl molecules, especially ones having multiple heteroatoms and other types of chiral elements, through radical routes remains extremely limited. We herein disclose the first catalytic asymmetric, metal-free construction of axially and centrally chiral heterobiaryls by Minisci reaction of 5-arylpyrimidines and α-amino acid-derived redox-active esters. This is

  轴向手性联芳基和杂联芳基构成阻转异构体中最具代表性的亚类，普遍存在于天然产物、生物活性化合物、特权手性配体/催化剂和光学纯材料中。尽管它们的构建有许多离子协议，但基于自由基的变体代表了另一种非常理想和有趣的策略，但远没有得到发展。此外，通过自由基途径有效合成轴向手性杂二芳基分子，尤其是具有多个杂原子和其他类型手性元素的分子仍然非常有限。我们在此披露了第一个通过 5-芳基嘧啶和 α-氨基酸衍生的氧化还原活性酯的 Minisci 反应构建的轴向和中心手性杂二芳基催化不对称、无金属结构。这是通过将 4CzIPN 用作有机光氧化还原催化剂与手性磷酸催化剂结合使用来实现的。该反应获得了多种有趣的 5-芳基嘧啶，其特征在于结合了一个轴向手性杂二芳基和一个中心手性 α-支化胺，具有通常优异的区域选择性、非对映选择性和对映选择性（高达 82% 的产率；>19:1 dr； >99% ee)。这一发现还为通过
• Atroposelective Synthesis of Axially Chiral Styrenes Connecting an Axially Chiral Naphthyl-indole Moiety Using Chiral Phosphoric Acid Catalysis
  作者：Alemayehu Gashaw Woldegiorgis、Haorui Gu、Xufeng Lin

  DOI：10.1021/acs.orglett.3c00425

  日期：2023.3.31

  The organocatalytic asymmetric reactions of C2-unsubstituted racemic naphthyl-indoles with orthoalkynylnaphthols were employed to synthesize axially chiral styrenes connected to an axially chiral naphthyl-indole unit. Utilizing chiral phosphoric acid as the catalyst, these axially chiral styrenes were prepared in good yields (up to 96%) and excellent stereoselectivity (up to >99.9% ee, >20:1 dr, and

  C2-未取代的外消旋萘基吲哚与邻炔基萘酚的有机催化不对称反应用于合成连接到轴向手性萘基吲哚单元的轴向手性苯乙烯。利用手性磷酸作为催化剂，这些轴向手性苯乙烯以良好的产率（高达 96%）和出色的立体选择性（高达 >99.9% ee、>20:1 dr 和 >99:1 E / Z ）在温和的条件。此外，以高产率和出色的立体控制实现了进一步的合成转化。
• New Drug-Like Hydroxyphenylnaphthol Steroidomimetics As Potent and Selective 17β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors for the Treatment of Estrogen-Dependent Diseases
  作者：Sandrine Marchais-Oberwinkler、Marie Wetzel、Erika Ziegler、Patricia Kruchten、Ruth Werth、Claudia Henn、Rolf W. Hartmann、Martin Frotscher

  DOI：10.1021/jm1009082

  日期：2011.1.27

  Inhibition of 17 beta-hydroxysteroid dehydrogenase type 1 (17 beta-HSD1) is a novel and attractive approach to reduce the local levels of the active estrogen 17 beta-estradiol in patients with estrogen-dependent diseases like breast cancer or endometriosis. With the aim of optimizing the biological profile of 17 beta-HSD1 inhibitors from the hydroxyphenylnaphthol class, structural optimizations were performed at the 1-position of the naphthalene by introduction of different heteroaromatic rings as well as substituted phenyl groups. In the latter class of compounds, which were synthesized applying Suzuki-cross coupling, the 3-methane-sulfonamide 15 turned out to be a highly potent 17 beta-HSD1 inhibitor (IC50 = 15 nM in a cell-free assay). It was also very active in the cellular assay (T47D cells, IC50 = 71 nM) and selective toward 17 beta-HSD2 and the estrogen receptors alpha and beta. It showed a good membrane permeation and metabolic stability and was orally available in the rat.
• Palladium-Catalyzed Enantioselective Synthesis of 2-Aryl Cyclohex-2-enone Atropisomers: Platform Molecules for the Divergent Synthesis of Axially Chiral Biaryl Compounds
  作者：Chongqing Pan、Zixi Zhu、Mingkai Zhang、Zhenhua Gu

  DOI：10.1002/anie.201701467

  日期：2017.4.18

  The palladium‐catalyzed asymmetric synthesis of enone‐based atropisomers from 2‐iodo‐3‐methylcyclohex‐2‐enones and aryl boronic acid is reported. BoPhoz‐type phosphine–aminophosphine ligands showed superior enantioselectivity over other ligands. These cyclohexenone‐based atropisomers are useful compounds for further elaboration. The divergent synthesis of biaryl atropisomers with different ortho substituents

  据报道，钯催化从2-碘-3-甲基环己-2-烯酮和芳基硼酸不对称合成基于烯酮的阻转异构体。BoPhoz型膦-氨基膦配体表现出优于其他配体的对映选择性。这些基于环己烯酮的阻转异构体是用于进一步完善的有用化合物。证明了具有不同邻取代基的联芳基阻转异构体的发散合成。