tert-butyl 3-[2-[(3S)-3-[3-[tert-butyl(diphenyl)silyl]oxypropyl]-3-ethyl-2-oxopiperidin-1-yl]ethyl]indole-1-carboxylate | 190378-45-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: tert-butyl 3-[2-[(3S)-3-[3-[tert-butyl(diphenyl)silyl]oxypropyl]-3-ethyl-2-oxopiperidin-1-yl]ethyl]indole-1-carboxylate
• CAS: 190378-45-1
• 化学式: C₄₁H₅₄N₂O₄Si
• 分子量: 666.976
• InChiKey: PQWNXNWETTXSDM-RWYGWLOXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.34
• 重原子数：
  48
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  60.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 3-[2-[(3S)-3-[3-[tert-butyl(diphenyl)silyl]oxypropyl]-3-ethyl-2-oxopiperidin-1-yl]ethyl]indole-1-carboxylate 在 palladium on activated charcoal ammonium hydroxide 、 重铬酸吡啶 、 聚合甲醛 、 甲酸 、 亚硝酸特丁酯 、 potassium tert-butylate 、 四丁基氟化铵 、 氢气 、 lithium perchlorate 、 sodium hexamethyldisilazane 、 对甲苯磺酸 、 三氯氧磷 作用下， 以 四氢呋喃 、 溶剂黄146 、 甲苯 为溶剂， 反应 47.67h， 生成 长春胺
  参考文献：
  名称：

  Stereocontrolled Elaboration of Quaternary Carbon Centers through the Asymmetric Michael-Type Alkylation of Chiral Imines/Secondary Enamines:  Enantioselective Synthesis of (+)-Vincamine

  摘要：

  An enantioselective synthesis of (+)-vincamine (1) has been developed. The key strategic element was the stereocontrolled elaboration of a quaternary carbon center (future C-20 center of 1) by using the asymmetric Michael reaction involving chiral imines/secondary enamines under neutral conditions. Thus, addition of enaminolactam (S)-12, derived from ketolactam 7 (itself prepared in four steps from commercially available tryptamine) and (S)-1-phenylethylamine, to methyl acrylate led, after hydrolytic workup, to adduct (R)-6 with a 90% stereoselectivity. The critical removal of the additional keto group of 6 was then examined. After extensive experimentation, we finally established that the most efficient deoxygenation procedure was the Wolff-Kishner reduction of the corresponding keto acid, which proceeded with a 55% yield. The cornerstone [ABD]-tricyclic lactam ester 38 thus obtained was next cyclized under Bischler-Napieralski reaction conditions to afford, after catalytic hydrogenation of the intermediary iminium perchlorate salt, a mixture of the desired, known indoloquinolizidine 5 and its epimer 39, in a ratio of 6:1, respectively. Basic treatment of 5 led to (+)-homoeburnamonine 4, which was finally converted, according to a known procedure, into our goal (+)-vincamine (1). Thus, synthesis of (+)-vincamine (1) has been achieved by a linear sequence of 15 chemical operations, starting from tryptamine, with an overall yield of 1.2%.

  DOI：

  10.1021/jo9622690
• 作为产物：
  描述：

  (3R)-3-ethyl-1-([2-(1H-indol-3-yl)ethyl]-3-{[3-(1,1-dimethylethyl)diphenylsilyl]oxy}propyl)-4-hydroxy-2-piperidinone 在 咪唑 、 偶氮二异丁腈 、 tri-n-butyl hydride 、 sodium hydride 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 6.25h， 生成 tert-butyl 3-[2-[(3S)-3-[3-[tert-butyl(diphenyl)silyl]oxypropyl]-3-ethyl-2-oxopiperidin-1-yl]ethyl]indole-1-carboxylate
  参考文献：
  名称：

  Stereocontrolled Elaboration of Quaternary Carbon Centers through the Asymmetric Michael-Type Alkylation of Chiral Imines/Secondary Enamines:  Enantioselective Synthesis of (+)-Vincamine

  摘要：

  An enantioselective synthesis of (+)-vincamine (1) has been developed. The key strategic element was the stereocontrolled elaboration of a quaternary carbon center (future C-20 center of 1) by using the asymmetric Michael reaction involving chiral imines/secondary enamines under neutral conditions. Thus, addition of enaminolactam (S)-12, derived from ketolactam 7 (itself prepared in four steps from commercially available tryptamine) and (S)-1-phenylethylamine, to methyl acrylate led, after hydrolytic workup, to adduct (R)-6 with a 90% stereoselectivity. The critical removal of the additional keto group of 6 was then examined. After extensive experimentation, we finally established that the most efficient deoxygenation procedure was the Wolff-Kishner reduction of the corresponding keto acid, which proceeded with a 55% yield. The cornerstone [ABD]-tricyclic lactam ester 38 thus obtained was next cyclized under Bischler-Napieralski reaction conditions to afford, after catalytic hydrogenation of the intermediary iminium perchlorate salt, a mixture of the desired, known indoloquinolizidine 5 and its epimer 39, in a ratio of 6:1, respectively. Basic treatment of 5 led to (+)-homoeburnamonine 4, which was finally converted, according to a known procedure, into our goal (+)-vincamine (1). Thus, synthesis of (+)-vincamine (1) has been achieved by a linear sequence of 15 chemical operations, starting from tryptamine, with an overall yield of 1.2%.

  DOI：

  10.1021/jo9622690

文献信息

• Stereocontrolled Elaboration of Quaternary Carbon Centers through the Asymmetric Michael-Type Alkylation of Chiral Imines/Secondary Enamines:  Enantioselective Synthesis of (+)-Vincamine
  作者：Didier Desmaële、Khalid Mekouar、Jean d'Angelo

  DOI：10.1021/jo9622690

  日期：1997.6.13

  An enantioselective synthesis of (+)-vincamine (1) has been developed. The key strategic element was the stereocontrolled elaboration of a quaternary carbon center (future C-20 center of 1) by using the asymmetric Michael reaction involving chiral imines/secondary enamines under neutral conditions. Thus, addition of enaminolactam (S)-12, derived from ketolactam 7 (itself prepared in four steps from commercially available tryptamine) and (S)-1-phenylethylamine, to methyl acrylate led, after hydrolytic workup, to adduct (R)-6 with a 90% stereoselectivity. The critical removal of the additional keto group of 6 was then examined. After extensive experimentation, we finally established that the most efficient deoxygenation procedure was the Wolff-Kishner reduction of the corresponding keto acid, which proceeded with a 55% yield. The cornerstone [ABD]-tricyclic lactam ester 38 thus obtained was next cyclized under Bischler-Napieralski reaction conditions to afford, after catalytic hydrogenation of the intermediary iminium perchlorate salt, a mixture of the desired, known indoloquinolizidine 5 and its epimer 39, in a ratio of 6:1, respectively. Basic treatment of 5 led to (+)-homoeburnamonine 4, which was finally converted, according to a known procedure, into our goal (+)-vincamine (1). Thus, synthesis of (+)-vincamine (1) has been achieved by a linear sequence of 15 chemical operations, starting from tryptamine, with an overall yield of 1.2%.