(8aR,9S,12R,12aS,12bR)-(+)-8a-[(1S,2R,4R,SS)-(2-hydroxy-7,7-dimethylbicyclo[2.2.1]heptan-1-yl)methylsulfinyl]-2,3-dimethoxy-12b-methyl-5,6,8a,9,12,12a-hexahydro-9,12-methaneisoindolin[2,3-a]isoquinolin-8-one | 446063-55-4

• 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: (8aR,9S,12R,12aS,12bR)-(+)-8a-[(1S,2R,4R,SS)-(2-hydroxy-7,7-dimethylbicyclo[2.2.1]heptan-1-yl)methylsulfinyl]-2,3-dimethoxy-12b-methyl-5,6,8a,9,12,12a-hexahydro-9,12-methaneisoindolin[2,3-a]isoquinolin-8-one
• 英文别名: (8aR,9S,12R,12aS,12bR)-(+)-8a-[(1S,2R,4R,S_R)-(2-hydroxy-7,7-dimethylbicyclo[2.2.1]heptan-1-yl)methylsulfinyl]-2,3-dimethoxy-12b-methyl-5,6,8a,9,12,12a-hexahydro-9,12-methaneisoindolin[2,3-a]isoquinolin-8-one；(1S,2S,3R,14R,15R)-14-[(R)-[(1S,2R,4R)-2-hydroxy-7,7-dimethyl-1-bicyclo[2.2.1]heptanyl]methylsulfinyl]-6,7-dimethoxy-3-methyl-12-azapentacyclo[13.2.1.02,14.03,12.04,9]octadeca-4,6,8,16-tetraen-13-one
• CAS: 446063-55-4
• 化学式: C₃₀H₃₉NO₅S
• 分子量: 525.709
• InChiKey: OVTNGKCLYCADHM-ZIZUDOPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  37
• 可旋转键数：
  5
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  95.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (8aR,9S,12R,12aS,12bR)-(+)-8a-[(1S,2R,4R,SS)-(2-hydroxy-7,7-dimethylbicyclo[2.2.1]heptan-1-yl)methylsulfinyl]-2,3-dimethoxy-12b-methyl-5,6,8a,9,12,12a-hexahydro-9,12-methaneisoindolin[2,3-a]isoquinolin-8-one 在 六甲基磷酰三胺 、 samarium diiodide 、 叔丁醇 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以83%的产率得到(8aS,9S,12R,12aS,12bR)-(+)-2,3-dimethoxy-12b-methyl-5,6,8a,9,12,12a-hexahydro-9,12-methaneisoindolin[2,3-a]isoquinolin-8-one
  参考文献：
  名称：

  基于非对映选择性帕拉姆环化和α-酰胺基烷基化反应的吡咯并[2,1- a ]异喹啉的对映异构体合成

  摘要：

  C-10b取代的吡咯并[2,1- a ]异喹啉的对映异构体合成是从对映体纯的N -phenethylnorborn-5-en-内酯-2,3-二羧酰亚胺3a与2- exo -hydroxy-10-bornylulfinyl作为手性助剂的基团已经开发出来。关键转化来自芳基锂的非对映选择性分子内环化反应和α-酰胺基烷基化反应，降冰片烯部分的亚乙基桥决定了这两种反应的立体化学结果。因此，酰亚胺3a上的有机锂加成-分子内α-酰胺基烷基化序列可立体选择性地提供R构型在C-12b处发生，而相应的碘化酰亚胺3b上的串联Parham环化-分子间α-酰胺基烷基化反应在完全控制立体选择性的情况下发生，从而导致C-12b上的差向异构体。随后还原性除去手性助剂和逆Diels-Alder反应，可得到高产率和光学纯度（> 99％ee）的（10b S）-和（10b R）-吡咯并异喹啉1。

  DOI：

  10.1021/jo049672o
• 作为产物：
  描述：

  (2R,6S)-4-[2-(3,4-dimethoxyphenyl)ethyl]-2-[(1S,2R,4R,S_R)-(2-hydroxy-7,7-dimethylbicyclo[2.2.1]hept-1-yl)methylsulfinyl]-4-aza-tricyclo[5.2.1.0^2,6]dec-8-ene-3,5-dione 以 四氢呋喃 、 二氯甲烷 、 正戊烷 为溶剂， 反应 78.0h， 生成 (8aR,9S,12R,12aS,12bR)-(+)-8a-[(1S,2R,4R,SS)-(2-hydroxy-7,7-dimethylbicyclo[2.2.1]heptan-1-yl)methylsulfinyl]-2,3-dimethoxy-12b-methyl-5,6,8a,9,12,12a-hexahydro-9,12-methaneisoindolin[2,3-a]isoquinolin-8-one
  参考文献：
  名称：

  N-苯乙基酰亚胺衍生的羟基内酰胺的高度非对映选择性分子内α-酰胺烷基化反应。二氢吡咯并[2,1-a]异喹诺酮类的对映选择性合成

  摘要：

  α-羟基内酰胺衍生自有机锂加成到对映异构纯的 N-phenethylnorborn-5-en-endo-2,3-dicarboxyimide 和 2-exo-hydroxy-10-bornylsulfinyl 基团作为手性助剂，进行高效和高度非对映选择性的 N-酰基胺离子环化。随后去除辅助和逆狄尔斯-阿尔德反应导致对映选择性合成 C-10b 取代的 5,6-二氢吡咯并 [2,1-a] 异喹啉。

  DOI：

  10.1055/s-2002-22703

文献信息

• Highly Diastereoselective Intramolecular α-Amidoalkylation Reactions of Hydroxylactams Derived from N-Phenethylimides. Enantioselective Synthesis of Dihydropyrrolo[2,1-a] isoquinolones
  作者：Inés González-Temprano、Nuria Sotomayor、Esther Lete

  DOI：10.1055/s-2002-22703

  日期：——

  α-Hydroxylactams, derived from organolithium addition to an enantiomerically pure N-phenethylnorborn-5-en-endo-2,3-dicarboxyimide with a 2-exo-hydroxy-10-bornylsulfinyl group as chiral auxiliary, undergo efficient and highly diastereoselective N-acyliminium ion cyclization. Subsequent removal of the auxiliary and retro-Diels-Alder reaction lead to the enantioselective synthesis of C-10b substituted

  α-羟基内酰胺衍生自有机锂加成到对映异构纯的 N-phenethylnorborn-5-en-endo-2,3-dicarboxyimide 和 2-exo-hydroxy-10-bornylsulfinyl 基团作为手性助剂，进行高效和高度非对映选择性的 N-酰基胺离子环化。随后去除辅助和逆狄尔斯-阿尔德反应导致对映选择性合成 C-10b 取代的 5,6-二氢吡咯并 [2,1-a] 异喹啉。
• Stereocontrolled conjugate additions to dihydroindolizinone systems. Synthesis of enantiopure polysubstituted tetrahydropyrrolo[2,1-a]isoquinolones
  作者：Cristina Camarero、Inés González-Temprano、Asier Gómez-SanJuan、Sonia Arrasate、Esther Lete、Nuria Sotomayor

  DOI：10.1016/j.tet.2009.05.011

  日期：2009.7

  Conjugate addition reactions of various types of nucleophiles to the gamma-lactam unit of dihydroindolizinone systems have been studied. The addition of cuprates, amines or stabilized carbanions requires the activation of the unsaturated bicyclic lactam with a EWG at C-2, while sulfur-stabilized carbanions are reactive enough to add to the unsubstituted lactam. The stereochemical outcome of the conjugate addition reaction depends on the nature of the substituent at the angular position, and the incoming nucleophile. Thus 1,10b-cis or 1,10b-trans diastereomers could be obtained selectively with dr>95:5. The tandem conjugate addition-alkylation also takes place in good yields. These reactions have been applied to the synthesis of enantiopure tetrahydropyrrolo [2,1-a]isoquinolines. (C) 2009 Elsevier Ltd. All rights reserved.
• Enantiodivergent Synthesis of Pyrrolo[2,1-<i>a</i>]isoquinolines Based on Diastereoselective Parham Cyclization and α-Amidoalkylation Reactions
  作者：Inés González-Temprano、Iñaki Osante、Esther Lete、Nuria Sotomayor

  DOI：10.1021/jo049672o

  日期：2004.5.1

  C-10b-substituted pyrrolo[2,1-a]isoquinolines starting from an enantiomerically pure N-phenethylnorborn-5-en-endo-2,3-dicarboxyimide 3a, with a 2-exo-hydroxy-10-bornylsulfinyl group as a chiral auxiliary, has been developed. The key transformations are derived from diastereoselective intramolecular cyclization of aryllithiums and α-amidoalkylation reactions, with the ethylidene bridge of the norbornene moiety

  C-10b取代的吡咯并[2,1- a ]异喹啉的对映异构体合成是从对映体纯的N -phenethylnorborn-5-en-内酯-2,3-二羧酰亚胺3a与2- exo -hydroxy-10-bornylulfinyl作为手性助剂的基团已经开发出来。关键转化来自芳基锂的非对映选择性分子内环化反应和α-酰胺基烷基化反应，降冰片烯部分的亚乙基桥决定了这两种反应的立体化学结果。因此，酰亚胺3a上的有机锂加成-分子内α-酰胺基烷基化序列可立体选择性地提供R构型在C-12b处发生，而相应的碘化酰亚胺3b上的串联Parham环化-分子间α-酰胺基烷基化反应在完全控制立体选择性的情况下发生，从而导致C-12b上的差向异构体。随后还原性除去手性助剂和逆Diels-Alder反应，可得到高产率和光学纯度（> 99％ee）的（10b S）-和（10b R）-吡咯并异喹啉1。