(4R)-4-ethyl-4-[(2S)-2-(methoxymethyl)pyrrolidine-1-carbonyl]-3-trimethylsilylcyclohexa-2,5-dien-1-one | 194656-44-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (4R)-4-ethyl-4-[(2S)-2-(methoxymethyl)pyrrolidine-1-carbonyl]-3-trimethylsilylcyclohexa-2,5-dien-1-one
• CAS: 194656-44-5
• 化学式: C₁₈H₂₉NO₃Si
• 分子量: 335.519
• InChiKey: BGUWSBOYWNWAGV-KSSFIOAISA-N

物化性质

• 沸点：
  426.3±45.0 °C(Predicted)
• 密度：
  1.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.96
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4R)-4-ethyl-4-[(2S)-2-(methoxymethyl)pyrrolidine-1-carbonyl]-3-trimethylsilylcyclohexa-2,5-dien-1-one 在 palladium on activated charcoal sodium hydroxide 、 锂硼氢 、 N-甲基吲哚酮 、 molecular sieve 、 四丙基高钌酸铵 、 叠氮磷酸二苯酯 、 硼烷 、 氢气 、 双氧水 、 potassium hydride 、 对甲苯磺酸 、 三乙胺 、 间氯过氧苯甲酸 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 苯 为溶剂， -55.0~55.0 ℃ 、434.37 kPa 条件下， 反应 134.5h， 生成 长春布宁
  参考文献：
  名称：

  Desymmetrization of Benzoic Acid in the Context of the Asymmetric Birch Reduction−Alkylation Protocol. Asymmetric Total Syntheses of (−)-Eburnamonine and (−)-Aspidospermidine

  摘要：

  The highly diastereoselective potassium in ammonia reduction-ethylation (EtI) of the chiral 2-(trimethylsilyl)benzamide 1b to give 1,4-cyclohexadiene 3 is the key step in asymmetric syntheses of (-)-eburnamonine (4) and (-)-aspidospermidine (5). Cyclohexadiene 3 was converted to cyclohexanone 7, which provided the trimethylsilyl-substituted butyrolactone 9 utilized for the synthesis of 4 and butyrolactone 13 required for the synthesis of 5. The preparation of 9 depended upon the completely regioselective silicon-directed Baeyer-Villiger oxidation 7-->8; Baeyer-Villiger oxidation of the cyclohexenone 10 also was regioselective to give the desired enol lactone 11 in 92% yield. Remarkable diastereoselectivity was observed for the kinetically controlled cyclization of the acyl imminium ion derived from the vinyl-substituted carboxaldehyde 16b; treatment of 16b with 5 equiv of CF3CO2H in CH2Cl2 at -55 degrees C gave an 18:1 mixture of 17 and its C(3) beta-epimer in 93% yield. The oxidation of alcohol 18 containing sensitive indole and piperidine rings was best carried out with tetrapropylammonium perruthenate/N-methylmorpholine N-oxide to give (-)-eburnamonine (4) in 97% yield. The asymmetric synthesis of (-)-aspidospermidine 5 involved the conversion of butyrolactone 13 to the hydroxylactam 22, the Harley-Mason cyclization of 22 to 23, and reduction of 23 with LiAlH4.

  DOI：

  10.1021/jo9707592
• 作为产物：
  描述：

  ((R)-1-Ethyl-2-trimethylsilanyl-cyclohexa-2,5-dienyl)-((S)-2-methoxymethyl-pyrrolidin-1-yl)-methanone 在 叔丁基过氧化氢 、 重铬酸吡啶 、 Celite 作用下， 以 苯 为溶剂， 反应 12.0h， 以90%的产率得到(4R)-4-ethyl-4-[(2S)-2-(methoxymethyl)pyrrolidine-1-carbonyl]-3-trimethylsilylcyclohexa-2,5-dien-1-one
  参考文献：
  名称：

  Desymmetrization of Benzoic Acid in the Context of the Asymmetric Birch Reduction−Alkylation Protocol. Asymmetric Total Syntheses of (−)-Eburnamonine and (−)-Aspidospermidine

  摘要：

  The highly diastereoselective potassium in ammonia reduction-ethylation (EtI) of the chiral 2-(trimethylsilyl)benzamide 1b to give 1,4-cyclohexadiene 3 is the key step in asymmetric syntheses of (-)-eburnamonine (4) and (-)-aspidospermidine (5). Cyclohexadiene 3 was converted to cyclohexanone 7, which provided the trimethylsilyl-substituted butyrolactone 9 utilized for the synthesis of 4 and butyrolactone 13 required for the synthesis of 5. The preparation of 9 depended upon the completely regioselective silicon-directed Baeyer-Villiger oxidation 7-->8; Baeyer-Villiger oxidation of the cyclohexenone 10 also was regioselective to give the desired enol lactone 11 in 92% yield. Remarkable diastereoselectivity was observed for the kinetically controlled cyclization of the acyl imminium ion derived from the vinyl-substituted carboxaldehyde 16b; treatment of 16b with 5 equiv of CF3CO2H in CH2Cl2 at -55 degrees C gave an 18:1 mixture of 17 and its C(3) beta-epimer in 93% yield. The oxidation of alcohol 18 containing sensitive indole and piperidine rings was best carried out with tetrapropylammonium perruthenate/N-methylmorpholine N-oxide to give (-)-eburnamonine (4) in 97% yield. The asymmetric synthesis of (-)-aspidospermidine 5 involved the conversion of butyrolactone 13 to the hydroxylactam 22, the Harley-Mason cyclization of 22 to 23, and reduction of 23 with LiAlH4.

  DOI：

  10.1021/jo9707592

文献信息

• Asymmetric synthesis of 4,4-disubstituted-2-cyclohexen-1-ones from a chiral 2-(trimethylsilyl)benzamide
  作者：Arthur G. Schultz、Liping Pettus

  DOI：10.1016/s0040-4039(97)01215-x

  日期：1997.8

  Birch reduction-alkylation of the chiral 2-(trimethylsilyl)benzamide 4 provides 1,4-cyclohexadienes 5b-5e with diastereomer ratios of >100:1. The conversions of 5b-5e to the 4,4-disubstituted-2-cyclohexen-1-ones 8b-8e are described. (C) 1997 Elsevier Science Ltd.
• Desymmetrization of Benzoic Acid in the Context of the Asymmetric Birch Reduction−Alkylation Protocol. Asymmetric Total Syntheses of (−)-Eburnamonine and (−)-Aspidospermidine
  作者：Arthur G. Schultz、Liping Pettus

  DOI：10.1021/jo9707592

  日期：1997.10.1

  The highly diastereoselective potassium in ammonia reduction-ethylation (EtI) of the chiral 2-(trimethylsilyl)benzamide 1b to give 1,4-cyclohexadiene 3 is the key step in asymmetric syntheses of (-)-eburnamonine (4) and (-)-aspidospermidine (5). Cyclohexadiene 3 was converted to cyclohexanone 7, which provided the trimethylsilyl-substituted butyrolactone 9 utilized for the synthesis of 4 and butyrolactone 13 required for the synthesis of 5. The preparation of 9 depended upon the completely regioselective silicon-directed Baeyer-Villiger oxidation 7-->8; Baeyer-Villiger oxidation of the cyclohexenone 10 also was regioselective to give the desired enol lactone 11 in 92% yield. Remarkable diastereoselectivity was observed for the kinetically controlled cyclization of the acyl imminium ion derived from the vinyl-substituted carboxaldehyde 16b; treatment of 16b with 5 equiv of CF3CO2H in CH2Cl2 at -55 degrees C gave an 18:1 mixture of 17 and its C(3) beta-epimer in 93% yield. The oxidation of alcohol 18 containing sensitive indole and piperidine rings was best carried out with tetrapropylammonium perruthenate/N-methylmorpholine N-oxide to give (-)-eburnamonine (4) in 97% yield. The asymmetric synthesis of (-)-aspidospermidine 5 involved the conversion of butyrolactone 13 to the hydroxylactam 22, the Harley-Mason cyclization of 22 to 23, and reduction of 23 with LiAlH4.