(S)-1-(4-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: (S)-1-(4-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
• 英文别名: (1S)-1-(4-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
• 化学式: C₁₇H₁₈ClNO₂
• 分子量: 303.788
• InChiKey: NYOFLAMHIMULAO-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-1-(4-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 、 乙酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 以94%的产率得到N-acetyl-1-(4-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Stereoselective Total Syntheses of Solifenacin and N-Acetyl-1-(4-chloro­phenyl)-6,7-dimethoxytetrahydroisoquinoline

  摘要：

  A highly stereoselective synthesis of 1-aryl-1,2,3,4-tetrahydroisoquinoline drugs such as solefinacin (muscarinic acetylcholine receptor antagonist) and N-acetyl-1-(4-chlorophenyl)-6,7-dimethoxytetrahydroisoquinoline (AMPA receptor antagonist) has been accomplished using (R)-tert-butanesulfinamide as a chiral source. Chiral tetrahydroisoquinolines have been prepared through the aryl Grignard addition to chiral N-sulfinylimines followed by haloamide cyclization.

  DOI：

  10.1055/s-0034-1378515
• 作为产物：
  描述：

  2-(3-(苄氧基)-4-甲氧基苯基)乙胺 在 盐酸 、 1,1’-bi-2-naphthol 、 palladium 10% on activated carbon 、 (R)-3,3′-bis(2,4,6-triisopropylphenyl)-BINOL-phosphoric acid 、 氢气 、 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 氯仿 、 甲苯 、 乙腈 为溶剂， 反应 22.25h， 生成 (S)-1-(4-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Organocatalytic Enantioselective Pictet–Spengler Reactions for the Syntheses of 1-Substituted 1,2,3,4-Tetrahydroisoquinolines

  摘要：

  A series of 1-substituted 1,2,3,4-tetrahydroisoquinolines was prepared from N-(o-nitrophenylsulfenyl)phenylethylamines through BINOL-phosphoric acid [(R)-TRIP]-catalyzed asymmetric Pictet-Spengler reactions. The sulfenamide moiety is crucial for the rate and enantioselectivity of the iminium ion cyclization and the products are readily recrystallized to high enantiomeric purity. Using this methodology we synthesized the natural products (R)-crispine A, (R)-calycotomine and (R)-colchietine, the synthetic drug (R)-almorexant and the (S)-enantiomer of a biologically active (R)-AMPA-antagonist.

  DOI：

  10.1021/jo501099h

文献信息

• [EN] CATALYSTS<br/>[FR] CATALYSEURS
  申请人：GOLDENKEYS HIGH TECH MAT CO LTD

  公开号：WO2020240178A1

  公开（公告）日：2020-12-03

  A compound, e.g. a diamine ligand, represented by the following general formula (1): (Formula (1)) wherein each * represents an asymmetric carbon atom; X represents a group selected from one of an ester (e.g. a t-butyl ester); a thioester; an amide; a heterocyclic moiety (e.g. a five-membered heterocyclic ring) comprising one or more of O, S, Se, and/or P (e.g. a furan, a tetrahydrofuran, a thiophene, an isoxazole, a bromo-furan, or a thiazole); a moiety (e.g. a five-membered heterocyclic ring) comprising a nitrogen atom, wherein the nitrogen atom is protected with a protecting group containing an electron-withdrawing group, preferably the protecting group is selected from one of a carbamate protecting group, an amide protecting group, an aryl sulphonamide protecting group, or an alkyl sulphonamide protecting group; and optionally X may additionally comprise a solid support, e.g. a polymeric or a silica particle; Y represents or is CtT'T'' where 't' is 0 or 1 and when 't' is 1 T' and T'' may individually represent a substituent, e.g. if t is 1, T' and/or T'' may each be hydrogen or deuterium atom, or a halogen atom; for example, Y may represent a carbon atom comprising two further substituents; Z represents a hydrogen atom or a deuterium atom; R1 represents an alkyl group (e.g. a functionalised alkyl group) preferably having between 1 to 100 carbon atoms, for example, between 1 to 30 carbon atoms (e.g. 1 to 20 carbon atoms, or 1 to 10 carbon atoms), a halogenated alkyl group preferably having between 1 to 100 carbon atoms (e.g. CF3), for example, between 1 to 30 carbon atoms (e.g. 1 to 20 carbon atoms, or 1 to 10 carbon atoms), an aryl group preferably having between 5 to 100 carbon atoms, e.g. 6 to 30 carbon atoms and optionally having one or more substituents selected from alkyl groups preferably having 1 to 100 carbon atoms, e.g. 1 to 10 carbon atoms, halogenated alkyl groups preferably having 1 to 100 carbon atoms, e.g. 1 to 10 carbon atoms, and/or halogen atoms; or R1 represents a solid support, e.g. a silica particle or a polymeric particle; R2 and R3 each independently represent a group selected from alkyl groups preferably having between 1 to 100 carbon atoms, for example 1 to 20 carbon atoms (e.g. 1 to 10 carbon atoms), aryl groups (e.g. phenyl groups), and cycloalkyl groups preferably having 3 to 8 carbon atoms, the aryl group or phenyl group optionally having one or more substituents selected from alkyl groups preferably having between 1 to 100 carbon atoms, e.g. between 1 to 20 carbon atoms (e.g. 1 to 10 carbon atoms), alkoxy groups preferably having between 1 to 100 carbon atoms, for example, between 1 to 20 carbon atoms (e.g. 1 to 10 carbon atoms), and halogen atoms, and each hydrogen atom of the cycloalkyl groups being optionally replaced by an alkyl group preferably having between 1 to 100 carbon atoms, e.g. 1 to 20 carbon atoms (e.g. 1 to 10 carbon atoms), or R1 represents a polyethylene glycol (PEG) moiety having the formula C2nH4n+2On+1 wherein n is an integer between 1 and 100; or R2 and R3 form a ring together with carbon atoms to which R2 and R3 are bonded; R4 represents a hydrogen atom or a deuterium atom.

  一个化合物，例如一种二胺配体，由以下一般式（1）表示：（公式（1））其中每个*代表一个不对称碳原子；X代表从酯（例如叔丁基酯）中选择的一个基团；硫酯；酰胺；一个杂环基团（例如一个含有O、S、Se和/或P的五元杂环环）；一个含有氮原子的基团，其中氮原子被含有电子吸引基团的保护基团保护，优选的保护基团从碳酸酯保护基团、酰胺保护基团、芳基磺酰胺保护基团或烷基磺酰胺保护基团中选择；可选地，X还可以包括固体支撑，例如聚合物或二氧化硅颗粒；Y代表或是CtT'T''，其中't'为0或1，当't'为1时，T'和T''可以分别代表一个取代基，例如，如果t为1，T'和/或T''可以分别是氢或氘原子，或卤原子；例如，Y可以代表一个包含两个进一步取代基的碳原子；Z代表氢原子或氘原子；R1代表一个烷基基团（例如，一个官能化烷基基团），优选地具有1到100个碳原子，例如，具有1到30个碳原子（例如，1到20个碳原子，或1到10个碳原子），一种卤代烷基基团，优选地具有1到100个碳原子（例如CF3），例如，具有1到30个碳原子（例如，1到20个碳原子，或1到10个碳原子），一种芳基基团，优选地具有5到100个碳原子，例如6到30个碳原子，并且可选地具有一个或多个取代基，所述取代基从烷基基团中选择，优选地具有1到100个碳原子，例如，1到10个碳原子，卤代烷基基团，优选地具有1到100个碳原子，例如，1到10个碳原子，和/或卤原子；或R1代表固体支撑，例如二氧化硅颗粒或聚合物颗粒；R2和R3各自独立地代表从烷基基团中选择的一个基团，优选地具有1到100个碳原子，例如1到20个碳原子（例如1到10个碳原子），芳基基团（例如苯基基团）和环烷基基团，优选地具有3到8个碳原子，所述芳基基团或苯基基团可选地具有一个或多个取代基，所述取代基从烷基基团中选择，优选地具有1到100个碳原子，例如，1到20个碳原子（例如，1到10个碳原子），烷氧基基团，优选地具有1到100个碳原子，例如，1到20个碳原子（例如，1到10个碳原子），和卤原子，所述环烷基基团的每个氢原子可选地被烷基基团替换，优选地具有1到100个碳原子，例如，1到20个碳原子（例如，1到10个碳原子），或R1代表具有公式C2nH4n+2On+1的聚乙二醇（PEG）基团，其中n是1到100之间的整数；或R2和R3与R2和R3结合的碳原子一起形成一个环；R4代表氢原子或氘原子。
• Enantioselective Synthesis of 1-Aryl-Substituted Tetrahydroisoquinolines Through Ru-Catalyzed Asymmetric Transfer Hydrogenation
  作者：Marc Perez、Zi Wu、Michelangelo Scalone、Tahar Ayad、Virginie Ratovelomanana-Vidal

  DOI：10.1002/ejoc.201500951

  日期：2015.9

  A convenient and general asymmetric transfer hydrogenation of a wide array of 1-aryl-3,4-dihydroisoquinoline derivatives using a [RuIICl(η6-benzene)TsDPEN] complex in combination with a 5:2 HCOOH–Et3N azeotropic mixture as a hydrogen source was developed. Under mild reaction conditions, the described catalytic transformation secured a practical synthetic access to the corresponding valuable chiral

  使用 [RuIICl(η6-苯)TsDPEN] 配合物与 5:2 HCOOH-Et3N 共沸混合物作为氢源，方便且通用地对各种 1-芳基-3,4-二氢异喹啉衍生物进行不对称转移氢化已开发。在温和的反应条件下，所描述的催化转化确保了获得相应有价值的手性 1-芳基四氢异喹啉单元的实际合成途径，该单元具有高原子经济性、广泛的底物范围、高分离产率（高达 97%）和良好的对映选择性（高达99% ee)。发现反应的立体化学结果受催化剂结构和底物上存在的取代基的强烈影响。
• Asymmetric Transfer Hydrogenation of Unhindered and Non-Electron-Rich 1-Aryl Dihydroisoquinolines with High Enantioselectivity
  作者：Jonathan Barrios-Rivera、Yingjian Xu、Martin Wills

  DOI：10.1021/acs.orglett.0c02034

  日期：2020.8.21

  The use of arene/Ru/TsDPEN catalysts bearing a heterocyclic group on the TsDPEN in the asymmetric transfer hydrogenation (ATH) of dihydroisoquinolines (DHIQs) containing meta- or para-substituted aromatic groups at the 1-position results in the formation of products of high enantiomeric excess. Previously, only 1-(ortho-substituted)aryl DHIQs, or with an electron-rich fused ring gave products with

  在1位上含有间位或对位取代的芳族基团的二氢异喹啉（DHIQ）的不对称转移氢化（ATH）中，使用在TsDPEN上带有杂环基的芳烃/ Ru / TsDPEN催化剂会导致生成高对映体过量。以前，只有1-（邻位取代的）芳基DHIQ，或带有富电子的稠合环，才能得到高对映选择性的产物。因此，这种方法解决了亚胺ATH的长期挑战。
• Josiphos-Type Binaphane Ligands for Iridium-Catalyzed Enantioselective Hydrogenation of 1-Aryl-Substituted Dihydroisoquinolines
  作者：Huifang Nie、Yupu Zhu、Xiaomu Hu、Zhao Wei、Lin Yao、Gang Zhou、Pingan Wang、Ru Jiang、Shengyong Zhang

  DOI：10.1021/acs.orglett.9b03251

  日期：2019.11.1

  displayed excellent enantioselectivity and good reactivity in the asymmetric hydrogenation of challenging 1-aryl-substituted dihydroisoquinoline substrates (full conversions, up to >99% ee, 4000 TON). The use of 40% HBr (aqueous solution) as an additive dramatically improved the asymmetric induction of these catalysts. This transformation provided a highly efficient and enantioselective access to chiral

  描述了一系列Josiphos型双苯甲醚配体的简便合成方法和有用的应用。这些手性二膦的铱络合物在具有挑战性的1-芳基取代的二氢异喹啉底物的不对称氢化中显示出出色的对映选择性和良好的反应性（完全转化，高达> 99％ee，4000 TON）。使用40％HBr（水溶液）作为添加剂可显着改善这些催化剂的不对称诱导。该转化提供了对手性1-芳基取代的四氢异喹啉的高效和对映选择性的途径，这在天然产物和生物活性分子中非常重要且常见。
• Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation of 1-Aryl-Substituted Dihydroisoquinolines: Access to Valuable Chiral 1-Aryl-Tetrahydroisoquinoline Scaffolds
  作者：Zi Wu、Marc Perez、Michelangelo Scalone、Tahar Ayad、Virginie Ratovelomanana-Vidal

  DOI：10.1002/anie.201301134

  日期：2013.4.26

  Give me an H! Give me another H! The first general and highly enantioselective Ru‐catalyzed transfer hydrogenation of a wide range of 1‐aryl‐substituted 1,2,3,4‐dihydroisoquinolines is described. This atom‐economic reaction proceeds under mild conditions, allowing rapid access to the corresponding biologically relevant 1‐aryl‐tetrahydroisoquinoline derivatives, in high yields and enantioselectivities

  给我一个H！再给我一个H！描述了第一个普通的和高对映选择性的Ru催化的广泛的1-芳基取代的1,2,3,4-二氢异喹啉的转移加氢反应。这种原子经济反应在温和的条件下进行，可以快速获得相应的生物学相关的1-芳基-四氢异喹啉衍生物，且收率高，对映选择性高达99％。