(3R^*,3aS^*,6S^*,7aS^*)-3a-(1,3-Benzodioxol-5-yl)-2,3,3a,6,7,7a-hexahydro-6-methoxy-1-methylindol-3-ol | 74120-54-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: (3R^*,3aS^*,6S^*,7aS^*)-3a-(1,3-Benzodioxol-5-yl)-2,3,3a,6,7,7a-hexahydro-6-methoxy-1-methylindol-3-ol
• 英文别名: (3β,3aα,6α,7aα)-3a,6,7,7a-tetrahydro-6-methoxy-1-methyl-3a-<3,4-(methylenedioxy)phenyl>-3-indolinol；(3S,3aR,6R,7aR)-3a-(1,3-benzodioxol-5-yl)-6-methoxy-1-methyl-3,6,7,7a-tetrahydro-2H-indol-3-ol
• CAS: 74120-54-0
• 化学式: C₁₇H₂₁NO₄
• 分子量: 303.358
• InChiKey: RSVYHZWVTUPSEI-WBQNTZJQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  三甲基乙酰氯 、 (3R^*,3aS^*,6S^*,7aS^*)-3a-(1,3-Benzodioxol-5-yl)-2,3,3a,6,7,7a-hexahydro-6-methoxy-1-methylindol-3-ol 在 吡啶 作用下， 以83%的产率得到(3R^*,3aS^*,6S^*,7aS^*)-3a-(1,3-Benzodioxol-5-yl)-2,3,3a,6,7,7a-hexahydro-6-methoxy-1-methyl-3-(pivaloyloxy)indole
  参考文献：
  名称：

  钌催化的N-（环己-2-烯基）-α-氯代-α-（苯硫基）乙酰胺的原子转移环化。（±）-山梨啶和（±）-Pretazettine的正式全合成

  摘要：

  氢吲哚（18）以前是全合成（±）-甘露定（2）和（±）-Pretazettine（1）的关键中间体，它是通过高度立体控制的方式通过涉及钌催化的α-氯硫化物的原子转移环化。

  DOI：

  10.1039/c39890001767
• 作为产物：
  描述：

  4-溴-1,2-亚甲二氧基苯 在 tris(triphenylphosphine)ruthenium(II) chloride 2,6-二甲基吡啶 、 N-氯代丁二酰亚胺 、 N-溴代丁二酰亚胺(NBS) 、 lithium aluminium tetrahydride 、 碳酸氢钠 、 对甲苯磺酸 、 magnesium 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 间氯过氧苯甲酸 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 二氯甲烷 、 水 、 乙腈 、 苯 为溶剂， 反应 45.75h， 生成 (3R^*,3aS^*,6S^*,7aS^*)-3a-(1,3-Benzodioxol-5-yl)-2,3,3a,6,7,7a-hexahydro-6-methoxy-1-methylindol-3-ol
  参考文献：
  名称：

  Ruthenium-catalyzed chlorine atom transfer cyclizations of N-allylic .alpha.-chloro-.alpha.-thioacetamides. Synthesis of (-)-trachelanthamidine and formal total synthesis of (.+-.)-haemanthidine and (.+-.)-pretazettine

  摘要：

  A new method for the synthesis of five-membered lactams by ruthenium-catalyzed chlorine atom transfer cyclizations of N-allylic alpha-chloro-alpha-thioacetamides and the application of the method to the synthesis of the title alkaloids are described. A benzene solution of N-allyl-N-methyl-alpha-chloro-alpha-(phenylthio)acetamide (6) was heated at 140-degrees-C in the presence of RuCl2(PPh3)3 to give alpha-thio-beta-(chloromethyl)-substituted gamma-lactam 8 as a mixture of cis and trans isomers in a ratio of ca. 3:7. NH congener 11, however, gave no cyclization product. Heating chloro sulfides 18 and 19, prepared from L-prolinol, with RuCl2(PPh3)3 afforded bicyclic lactams 20 and 21, respectively. Treatment of 20 with cesium propanoate gave predominantly cyclopropane derivative 25, whereas S-methyl congener 21 provided esters 24 in good yield. Desulfurization of 24 with Raney nickel followed by reduction with LiAlH4 furnished (-)-trachelanthamidine (28). On the other hand, N-(cyclohex-2-en-1-yl) derivative 30, when heated with RuCl2(PPh3)3, afforded octahydroindol-2-ones 31a,b. The formation of 31a,b indicated that the intramolecular addition of the chloro sulfide of 30 to the olefinic bond proceeded in an anti-mode. By contrast, 2-phenyl-substituted derivative 38 gave syn-addition product 39. The difference between the modes of cyclization of 30 and 38 can be explained by assuming the intermediacy of radical 34. When R = H, the chlorine atom attacks the convex face of the fused bicyclic system of 34 to lead to 31a,b, whereas the steric bulk of the angular phenyl group (R = Ph) is apparently sufficient to direct the chlorine atom to the concave face. Heating chloro sulfide 48, prepared in a highly stereocontrolled manner from cyclohexene 42, with RuCl2(PPh3)3 afforded bicyclic lactam 49. Oxidation of 49 with m-CPBA followed by Pummerer rearrangement/hydrolysis gave keto lactam 51, which was dehydrochlorinated with DBU to give olefin 52. LiAlH4 reduction of 52 and acylation with pivaloyl chloride provided ester 54, a key intermediate in Martin's total synthesis of (+/-)-haemanthidine (41) and (+/-)-pretazettine (40).

  DOI：

  10.1021/jo00061a005

文献信息

• Ruthenium-catalysed atom-transfer cyclisation of N-(cyclohex-2-enyl)-α-chloro-α-(phenylthio)acetamides. A formal total synthesis of (±)-haemanthidine and (±)-pretazettine
  作者：Hiroyuki Ishibashi、Hiroshi Nakatani、Satoshi Iwami、Tatsunori Sato、Nobuyuki Nakamura、Masazumi Ikeda

  DOI：10.1039/c39890001767

  日期：——

  The hydroindole (18), which previously served as a key intemediate in the total synthesis of (±)-haemanthidine (2) and (±)-pretazettine (1), has been prepared in a highly stereocontrolled manner by a reaction sequence involving a ruthenium-catalysed atom-transfer cyclisation of an α-chloro sulphide.

  氢吲哚（18）以前是全合成（±）-甘露定（2）和（±）-Pretazettine（1）的关键中间体，它是通过高度立体控制的方式通过涉及钌催化的α-氯硫化物的原子转移环化。
• Total synthesis of dl-tazettine and 6a-epipretazettine: a formal synthesis of dl-pretazettine. Some observations on the relationship of 6a-epipretazettine and tazettine
  作者：Samuel Danishefsky、Joel Morris、George Mullen、Ronald Gammill

  DOI：10.1021/ja00390a034

  日期：1982.12
• Total synthesis of dl-tazettine
  作者：Samuel Danishefsky、Joel Morris、George Mullen、Ronald Gammill

  DOI：10.1021/ja00528a054

  日期：1980.4
• Ruthenium-catalyzed chlorine atom transfer cyclizations of N-allylic .alpha.-chloro-.alpha.-thioacetamides. Synthesis of (-)-trachelanthamidine and formal total synthesis of (.+-.)-haemanthidine and (.+-.)-pretazettine
  作者：Hiroyuki Ishibashi、Nahoko Uemura、Hiroshi Nakatani、Mika Okazaki、Tatsunori Sato、Nobuyuki Nakamura、Masazumi Ikeda

  DOI：10.1021/jo00061a005

  日期：1993.4

  A new method for the synthesis of five-membered lactams by ruthenium-catalyzed chlorine atom transfer cyclizations of N-allylic alpha-chloro-alpha-thioacetamides and the application of the method to the synthesis of the title alkaloids are described. A benzene solution of N-allyl-N-methyl-alpha-chloro-alpha-(phenylthio)acetamide (6) was heated at 140-degrees-C in the presence of RuCl2(PPh3)3 to give alpha-thio-beta-(chloromethyl)-substituted gamma-lactam 8 as a mixture of cis and trans isomers in a ratio of ca. 3:7. NH congener 11, however, gave no cyclization product. Heating chloro sulfides 18 and 19, prepared from L-prolinol, with RuCl2(PPh3)3 afforded bicyclic lactams 20 and 21, respectively. Treatment of 20 with cesium propanoate gave predominantly cyclopropane derivative 25, whereas S-methyl congener 21 provided esters 24 in good yield. Desulfurization of 24 with Raney nickel followed by reduction with LiAlH4 furnished (-)-trachelanthamidine (28). On the other hand, N-(cyclohex-2-en-1-yl) derivative 30, when heated with RuCl2(PPh3)3, afforded octahydroindol-2-ones 31a,b. The formation of 31a,b indicated that the intramolecular addition of the chloro sulfide of 30 to the olefinic bond proceeded in an anti-mode. By contrast, 2-phenyl-substituted derivative 38 gave syn-addition product 39. The difference between the modes of cyclization of 30 and 38 can be explained by assuming the intermediacy of radical 34. When R = H, the chlorine atom attacks the convex face of the fused bicyclic system of 34 to lead to 31a,b, whereas the steric bulk of the angular phenyl group (R = Ph) is apparently sufficient to direct the chlorine atom to the concave face. Heating chloro sulfide 48, prepared in a highly stereocontrolled manner from cyclohexene 42, with RuCl2(PPh3)3 afforded bicyclic lactam 49. Oxidation of 49 with m-CPBA followed by Pummerer rearrangement/hydrolysis gave keto lactam 51, which was dehydrochlorinated with DBU to give olefin 52. LiAlH4 reduction of 52 and acylation with pivaloyl chloride provided ester 54, a key intermediate in Martin's total synthesis of (+/-)-haemanthidine (41) and (+/-)-pretazettine (40).