(6S)-[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy]-3-phenyl-6H-1,2-oxazine | 205764-47-2

• 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: (6S)-[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy]-3-phenyl-6H-1,2-oxazine
• 英文别名: (6S)-6-[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl]oxy-3-phenyl-6H-oxazine
• CAS: 205764-47-2
• 化学式: C₂₀H₂₇NO₂
• 分子量: 313.44
• InChiKey: PLNDFWNAYAUPBX-VUBSUSDNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  30.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (6S)-[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy]-3-phenyl-6H-1,2-oxazine 在 ruthenium trichloride 、 sodium periodate 作用下， 以 水 、 乙酸乙酯 、 乙腈 为溶剂， 生成
  参考文献：
  名称：

  通过 1,2-恶嗪的还原环收缩立体选择性制备二羟基化吡咯烷

  摘要：

  通过使用 BH 3 ·THF 立体选择性还原 C=N 键，将受保护的二羟基化 1,2-恶嗪衍生物如 RAC-4 转化为四氢-1,2-恶嗪 RAC-7。在钯炭存在下，化合物7A在氢化时经历还原环收缩，从而以良好的产率提供RAC-5。使用 (-)-薄荷醇作为手性助剂制备对映体纯 1,2-恶嗪衍生物 13 和 14。它们的非对映选择性二羟基化和 BH 3 ·THF 还原以良好的总产率提供对映纯的四氢-2 H-1,2-恶嗪衍生物 17 和 18。对映异构体 (6 R)-18 和 (6 S)-18 以中等收率转化为两种对映异构体羟基化吡咯烷衍生物 5。

  DOI：

  10.1055/s-2007-983802
• 作为产物：
  描述：

  L-薄荷醇 、 6-乙氧基-3-苯基-6H-1,2-恶嗪 在 三氟化硼乙醚 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以28%的产率得到(6S)-[(1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy]-3-phenyl-6H-1,2-oxazine
  参考文献：
  名称：

  Synthesis of Enantioenriched 2-Substituted 4-Phenylbutylamines by Hydrogenolysis of Optically Pure 6-Alkoxy-5,6-dihydro-4H-1,2-oxazines

  摘要：

  Lewis acid promoted exchange of the 6-ethoxy group of 6H-1,2-oxazines 1-3 with (-)-menthol furnished the optically active heterocycles 4-6. Diastereomers 4a and 4b, which could be separated efficiently by chromatography, were excellent substrates for highly diastereoselective conjugate additions of phenyllithium and n-butyllithium, thus providing the enantiopure trans-substituted 1,2-oxazines 7a, 7b, 8a, and 8b in good yields. Exhaustive hydrogenolysis of 7a afforded the primary amine 9 with an enantiomeric excess of 80%, whereas hydrogenolysis of 8a and 8b gave the corresponding amines (R)-11 and (S)-11, respectively, with an ee of more than 90%. (C) Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.

  DOI：

  10.1002/1099-0690(200208)2002:16<2838::aid-ejoc2838>3.0.co;2-o

文献信息

• 1,2-Oxazines as Building Blocks for Stereoselective Synthesis: Preparation of Oxygen-Substituted 1,2-Oxazines, either by Alcohol Addition or by Epoxidation, and Subsequent Hydrogenation Leading to 1,2-Amino Alcohols and Pyrrolidines
  作者：Reinhold Zimmer、Monika Buchholz、Markus Collas、Jörg Angermann、Kai Homann、Hans-Ulrich Reissig

  DOI：10.1002/ejoc.201000425

  日期：2010.7

  corresponding epoxides 25 and 32 in reasonable to excellent yields. It was demonstrated that the resulting oxygen-substituted 1,2-oxazines were suitable precursors for the preparation of cyclic or acyclic primary and secondary amines in racemic or enantiopure form. Hydrogenation of the 3-phenyl-substituted 1,2-oxazines 3 and 25a and of (6S)- and (6R)-32 preferentially furnished the 1,2-amino alcohols

  立体定义的氧取代 1,2-恶嗪通过三种不同的途径制备。烯醇醚如 1 与原位生成的 α-亚硝基烯烃的环加成得到杂环 3 和 4。醇在酸催化下加成到 6H-1,2-恶嗪 5 导致加合物 6 和取代产物 7 的混合物具有中等化学选择性。6H-1,2-恶嗪5的环氧化更有效地进行并且以合理到极好的产率提供相应的环氧化物25和32。结果表明，所得氧取代的 1,2-恶嗪是制备外消旋或对映纯形式的环状或非环状伯胺和仲胺的合适前体。3-苯基取代的1,2-恶嗪3和25a以及(6S)-和(6R)-32的氢化优先提供1,2-氨基醇15、rac-29 和 (2S)- 和 (2R)-29。另一方面，3-乙氧基羰基取代的1,2-恶嗪4、6d和20的还原导致以中等产率形成N-保护的脯氨酸酯21-24。还发现 5-甲基-6H-1,2-恶嗪 10 是炔丙醚 11 的良好前体，它允许 Pauson-Khand 反应产生三环化合物
• A Stereoselective Access to Dihydroxylated Pyrrolidines by Reductive Ring Contraction of 1,2-Oxazines
  作者：Hans-Ulrich Reissig、Reinhold Zimmer、Kai Homann、Florian Hiller

  DOI：10.1055/s-2007-983802

  日期：2007.9

  BH 3 ·THF for the stereoselective reduction of the C=N bond. Compound 7A underwent a reductive ring contraction on hydrogenation in the presence of palladium on charcoal to provide RAC- 5 in good yield. Enantiopure 1,2-oxazine derivatives 13 and 14 were prepared using (-)-menthol as chiral auxiliary. Their diastereo-selective dihydroxylation and BH 3 ·THF reduction furnished enantiopure tetrahydro-2

  通过使用 BH 3 ·THF 立体选择性还原 C=N 键，将受保护的二羟基化 1,2-恶嗪衍生物如 RAC-4 转化为四氢-1,2-恶嗪 RAC-7。在钯炭存在下，化合物7A在氢化时经历还原环收缩，从而以良好的产率提供RAC-5。使用 (-)-薄荷醇作为手性助剂制备对映体纯 1,2-恶嗪衍生物 13 和 14。它们的非对映选择性二羟基化和 BH 3 ·THF 还原以良好的总产率提供对映纯的四氢-2 H-1,2-恶嗪衍生物 17 和 18。对映异构体 (6 R)-18 和 (6 S)-18 以中等收率转化为两种对映异构体羟基化吡咯烷衍生物 5。
• Synthesis of Enantioenriched 2-Substituted 4-Phenylbutylamines by Hydrogenolysis of Optically Pure 6-Alkoxy-5,6-dihydro-4H-1,2-oxazines
  作者：Monika Buchholz、Florian Hiller、Hans-Ulrich Reißig

  DOI：10.1002/1099-0690(200208)2002:16<2838::aid-ejoc2838>3.0.co;2-o

  日期：2002.8

  Lewis acid promoted exchange of the 6-ethoxy group of 6H-1,2-oxazines 1-3 with (-)-menthol furnished the optically active heterocycles 4-6. Diastereomers 4a and 4b, which could be separated efficiently by chromatography, were excellent substrates for highly diastereoselective conjugate additions of phenyllithium and n-butyllithium, thus providing the enantiopure trans-substituted 1,2-oxazines 7a, 7b, 8a, and 8b in good yields. Exhaustive hydrogenolysis of 7a afforded the primary amine 9 with an enantiomeric excess of 80%, whereas hydrogenolysis of 8a and 8b gave the corresponding amines (R)-11 and (S)-11, respectively, with an ee of more than 90%. (C) Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.