(1S,4R,5R)-5-(6-Chloro-pyridin-3-yl)-2-oxa-3-aza-bicyclo[2.2.2]octane-3-carboxylic acid (1S,2R,5S)-5-methyl-2-(1-methyl-1-naphthalen-2-yl-ethyl)-cyclohexyl ester | 211503-90-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (1S,4R,5R)-5-(6-Chloro-pyridin-3-yl)-2-oxa-3-aza-bicyclo[2.2.2]octane-3-carboxylic acid (1S,2R,5S)-5-methyl-2-(1-methyl-1-naphthalen-2-yl-ethyl)-cyclohexyl ester
• 英文别名: [(1S,2R,5S)-5-methyl-2-(2-naphthalen-2-ylpropan-2-yl)cyclohexyl] (1S,4R,5R)-5-(6-chloropyridin-3-yl)-2-oxa-3-azabicyclo[2.2.2]octane-3-carboxylate
• CAS: 211503-90-1
• 化学式: C₃₂H₃₇ClN₂O₃
• 分子量: 533.11
• InChiKey: JRBHMVFVLLRBHO-MRZSSMFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.8
• 重原子数：
  38
• 可旋转键数：
  5
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  51.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1S,4R,5R)-5-(6-Chloro-pyridin-3-yl)-2-oxa-3-aza-bicyclo[2.2.2]octane-3-carboxylic acid (1S,2R,5S)-5-methyl-2-(1-methyl-1-naphthalen-2-yl-ethyl)-cyclohexyl ester 在 四溴化碳 、 lithium amidotrihydroborate 、 molybdenum hexacarbonyl 、 sodium carbonate 、 三苯基膦 、 三氟乙酸 作用下， 以 二氯甲烷 、 氯仿 、 水 、 乙腈 为溶剂， 反应 82.75h， 生成 (±)-三色素蛙素
  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：

  2-氯-5-碘吡啶 在 platinum(IV) oxide 四(三苯基膦)钯 、 草酰氯 、 氢气 、 magnesium 、 二甲基亚砜 、 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， -78.0~25.0 ℃ 、101.33 kPa 条件下， 反应 30.0h， 生成 (1S,4R,5R)-5-(6-Chloro-pyridin-3-yl)-2-oxa-3-aza-bicyclo[2.2.2]octane-3-carboxylic acid (1S,2R,5S)-5-methyl-2-(1-methyl-1-naphthalen-2-yl-ethyl)-cyclohexyl ester
  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.