({(1R,2S,5R)-5-methyl-2-[1-methyl-1-(4-nitrophenyl)ethyl]cyclohexyl}oxy)carbonylhydroxylamine | 217323-86-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: ({(1R,2S,5R)-5-methyl-2-[1-methyl-1-(4-nitrophenyl)ethyl]cyclohexyl}oxy)carbonylhydroxylamine
• 英文别名: [(1R,2S,5R)-5-methyl-2-[2-(4-nitrophenyl)propan-2-yl]cyclohexyl] N-hydroxycarbamate
• CAS: 217323-86-9
• 化学式: C₁₇H₂₄N₂O₅
• 分子量: 336.388
• InChiKey: WOXUKALPQWRCQY-KCPJHIHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1,3-环己二烯 、 ({(1R,2S,5R)-5-methyl-2-[1-methyl-1-(4-nitrophenyl)ethyl]cyclohexyl}oxy)carbonylhydroxylamine 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 生成 [(1R,2S,5R)-5-methyl-2-[2-(4-nitrophenyl)propan-2-yl]cyclohexyl] (1S,4R)-2-oxa-3-azabicyclo[2.2.2]oct-5-ene-3-carboxylate 、 [(1R,2S,5R)-5-methyl-2-[2-(4-nitrophenyl)propan-2-yl]cyclohexyl] (1R,4S)-2-oxa-3-azabicyclo[2.2.2]oct-5-ene-3-carboxylate
  参考文献：
  名称：

  Total Synthesis of (−)-Epibatidine Using an Asymmetric Diels−Alder Reaction with a Chiral N-Acylnitroso Dienophile

  摘要：

  An asymmetric total synthesis of(-)-epibatidine (1), isolated from the skin of the Ecuadorian poison frog, Epipedobates tricolor, of the family Dendrobatidae, has been achieved by virtue of the development of asymmetric hetero Diels-Alder (D-A) cycloaddition with an N-acylnitroso dienophile bearing the optically active 8-arylmenthol as a chiral source. Thus, in situ oxidation of the hydroxamic acid ent-laf incorporating the (1S,2R,5S)-8-(2-naphthyl)menthyl auxiliary was performed using the Swern conditions to produce the acylnitroso dienophile, which reacted at once with 2-chloro-5-(1,5-cyclohexadienyl)pyridine (7) to provide the (1S,4R)-meta-aza cycloadduct 24 as a major diastereoisomer. The observed facial diastereoselectivity is consistent with a transition-state model with the naphthyl group in "stacked" position and with the acylnitroso group in the s-cis conformation, wherein pi attractive interaction between the naphthyl and nitrosocarbonyl groups may contribute to facial control. Compound 24 underwent hydrogenation followed by removal of the chiral auxiliary with LiH2NBH3 and reductive cleavage of the N-O bond with Mo(CO)(6) to give the amino alcohol derivative 29, which was converted to (-)-epibatidine via bromination followed by cyclization.

  DOI：

  10.1021/jo9813078
• 作为产物：
  描述：

  长叶薄荷酮 在 吡啶 、 copper(I) bromide 、 4-二甲氨基吡啶 、 氢氧化钾 、 硝酸铵 、 N,O-双三甲硅基羟胺 、 sodium 、 异丙醇 、 三氟乙酸酐 作用下， 以 甲醇 、 氯仿 、 水 为溶剂， 反应 32.5h， 生成 ({(1R,2S,5R)-5-methyl-2-[1-methyl-1-(4-nitrophenyl)ethyl]cyclohexyl}oxy)carbonylhydroxylamine
  参考文献：
  名称：

  Total Synthesis of (−)-Epibatidine Using an Asymmetric Diels−Alder Reaction with a Chiral N-Acylnitroso Dienophile

  摘要：

  An asymmetric total synthesis of(-)-epibatidine (1), isolated from the skin of the Ecuadorian poison frog, Epipedobates tricolor, of the family Dendrobatidae, has been achieved by virtue of the development of asymmetric hetero Diels-Alder (D-A) cycloaddition with an N-acylnitroso dienophile bearing the optically active 8-arylmenthol as a chiral source. Thus, in situ oxidation of the hydroxamic acid ent-laf incorporating the (1S,2R,5S)-8-(2-naphthyl)menthyl auxiliary was performed using the Swern conditions to produce the acylnitroso dienophile, which reacted at once with 2-chloro-5-(1,5-cyclohexadienyl)pyridine (7) to provide the (1S,4R)-meta-aza cycloadduct 24 as a major diastereoisomer. The observed facial diastereoselectivity is consistent with a transition-state model with the naphthyl group in "stacked" position and with the acylnitroso group in the s-cis conformation, wherein pi attractive interaction between the naphthyl and nitrosocarbonyl groups may contribute to facial control. Compound 24 underwent hydrogenation followed by removal of the chiral auxiliary with LiH2NBH3 and reductive cleavage of the N-O bond with Mo(CO)(6) to give the amino alcohol derivative 29, which was converted to (-)-epibatidine via bromination followed by cyclization.

  DOI：

  10.1021/jo9813078

文献信息

• Total Synthesis of (−)-Epibatidine Using an Asymmetric Diels−Alder Reaction with a Chiral <i>N</i>-Acylnitroso Dienophile
  作者：Sakae Aoyagi、Ryuta Tanaka、Masaichi Naruse、Chihiro Kibayashi

  DOI：10.1021/jo9813078

  日期：1998.11.1

  An asymmetric total synthesis of(-)-epibatidine (1), isolated from the skin of the Ecuadorian poison frog, Epipedobates tricolor, of the family Dendrobatidae, has been achieved by virtue of the development of asymmetric hetero Diels-Alder (D-A) cycloaddition with an N-acylnitroso dienophile bearing the optically active 8-arylmenthol as a chiral source. Thus, in situ oxidation of the hydroxamic acid ent-laf incorporating the (1S,2R,5S)-8-(2-naphthyl)menthyl auxiliary was performed using the Swern conditions to produce the acylnitroso dienophile, which reacted at once with 2-chloro-5-(1,5-cyclohexadienyl)pyridine (7) to provide the (1S,4R)-meta-aza cycloadduct 24 as a major diastereoisomer. The observed facial diastereoselectivity is consistent with a transition-state model with the naphthyl group in "stacked" position and with the acylnitroso group in the s-cis conformation, wherein pi attractive interaction between the naphthyl and nitrosocarbonyl groups may contribute to facial control. Compound 24 underwent hydrogenation followed by removal of the chiral auxiliary with LiH2NBH3 and reductive cleavage of the N-O bond with Mo(CO)(6) to give the amino alcohol derivative 29, which was converted to (-)-epibatidine via bromination followed by cyclization.