cis-3-benzyloxy-4-hydroxy-1-isopropylpiperidine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: cis-3-benzyloxy-4-hydroxy-1-isopropylpiperidine
• 英文别名: (3R,4S)-3-phenylmethoxy-1-propan-2-ylpiperidin-4-ol
• 化学式: C₁₅H₂₃NO₂
• 分子量: 249.353
• InChiKey: JDZPMJMXTIBDNG-LSDHHAIUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  32.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  cis-3-benzyloxy-4-hydroxy-1-isopropylpiperidine 、 (1S)-(-)-莰烷酰氯 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 生成
  参考文献：
  名称：

  Synthesis of piperidin-4-ones starting from 2-(2-bromo-1,1-dimethylethyl)azetidines and 2-(2-mesyloxyethyl)azetidines through a ring expansion–oxidation protocol

  摘要：

  cis-2-(2-Bromo-1,1-dimethylethyl)azetidines were transformed into novel 5,5-dimethylpiperidin-4-ones through a ring expansion oxidation protocol upon heating in DMSO in the presence of Ag2CO3 or AgBF4. In addition, several 5,5-nor-dimethyl analogues of the latter piperidin-4-ones were synthesized in a selective way through a similar ring expansion oxidation approach involving treatment of cis-2-(2-mesyloxyethyl)azetidines with K2CO3 in DMSO. Furthermore, both a diastereoselective and an enantioselective reduction of the carbonyl function in piperidin-4-ones were performed through a chemical and an enzymatic approach, respectively. Whereas the NaBH4-induced reduction proceeded with cis-diastereoselectivity, alcohol dehydrogenase-mediated reductions resulted in either an S- or R-enantioselectivity. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2013.01.045
• 作为产物：
  描述：

  (E)-N-[3-(tert-butyldimethylsilyloxy)propylidene]isopropylamine 在 4-二甲氨基吡啶 、 aluminum (III) chloride 、 lithium aluminium tetrahydride 、 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 、 乙腈 为溶剂， 反应 21.0h， 生成 cis-3-benzyloxy-4-hydroxy-1-isopropylpiperidine
  参考文献：
  名称：

  通过2-（2-甲氧基氧乙基）氮杂环丁烷的环转化立体选择性合成顺式-3,4-二取代的哌啶

  摘要：

  首次评估了通过一氯丙烷还原和相应的β-内酰胺甲磺酸化获得的2-（2-甲氧基氧乙基）氮杂环丁烷对不同亲核试剂的反应性，从而立体选择性地制备了多种新的4-乙酰氧基-，4-羟基-，4-溴-和4-甲酰氧基哌啶。在这些反应过程中，短暂的1-azoniabicyclo [2.2.0]己烷易于经历S N 2型开环，以提供最终的氮杂杂环，这可以通过详细的计算分析加以合理化。该方法构成了已知制备3,4-二取代的5,5-二甲基哌啶的方便替代方法，可轻松获得5,5-去甲二甲基类似物，作为药物化学中的重要模板。此外，顺式通过脱氢溴化然后酸水解，将-4-溴-3-（苯氧基或苄氧基）哌啶精制到哌啶-3-酮骨架中。

  DOI：

  10.1021/jo201556t

文献信息

• Synthesis of piperidin-4-ones starting from 2-(2-bromo-1,1-dimethylethyl)azetidines and 2-(2-mesyloxyethyl)azetidines through a ring expansion–oxidation protocol
  作者：Karen Mollet、Matthias D'hooghe、Leen Broeckx、Barbara Danneels、Tom Desmet、Norbert De Kimpe

  DOI：10.1016/j.tet.2013.01.045

  日期：2013.3

  cis-2-(2-Bromo-1,1-dimethylethyl)azetidines were transformed into novel 5,5-dimethylpiperidin-4-ones through a ring expansion oxidation protocol upon heating in DMSO in the presence of Ag2CO3 or AgBF4. In addition, several 5,5-nor-dimethyl analogues of the latter piperidin-4-ones were synthesized in a selective way through a similar ring expansion oxidation approach involving treatment of cis-2-(2-mesyloxyethyl)azetidines with K2CO3 in DMSO. Furthermore, both a diastereoselective and an enantioselective reduction of the carbonyl function in piperidin-4-ones were performed through a chemical and an enzymatic approach, respectively. Whereas the NaBH4-induced reduction proceeded with cis-diastereoselectivity, alcohol dehydrogenase-mediated reductions resulted in either an S- or R-enantioselectivity. (C) 2013 Elsevier Ltd. All rights reserved.
• Stereoselective Synthesis of <i>cis</i>-3,4-Disubstituted Piperidines through Ring Transformation of 2-(2-Mesyloxyethyl)azetidines
  作者：Karen Mollet、Saron Catak、Michel Waroquier、Veronique Van Speybroeck、Matthias D’hooghe、Norbert De Kimpe

  DOI：10.1021/jo201556t

  日期：2011.10.21

  The reactivity of 2-(2-mesyloxyethyl)azetidines, obtained through monochloroalane reduction and mesylation of the corresponding β-lactams, with regard to different nucleophiles was evaluated for the first time, resulting in the stereoselective preparation of a variety of new 4-acetoxy-, 4-hydroxy-, 4-bromo-, and 4-formyloxypiperidines. During these reactions, transient 1-azoniabicyclo[2.2.0]hexanes

  首次评估了通过一氯丙烷还原和相应的β-内酰胺甲磺酸化获得的2-（2-甲氧基氧乙基）氮杂环丁烷对不同亲核试剂的反应性，从而立体选择性地制备了多种新的4-乙酰氧基-，4-羟基-，4-溴-和4-甲酰氧基哌啶。在这些反应过程中，短暂的1-azoniabicyclo [2.2.0]己烷易于经历S N 2型开环，以提供最终的氮杂杂环，这可以通过详细的计算分析加以合理化。该方法构成了已知制备3,4-二取代的5,5-二甲基哌啶的方便替代方法，可轻松获得5,5-去甲二甲基类似物，作为药物化学中的重要模板。此外，顺式通过脱氢溴化然后酸水解，将-4-溴-3-（苯氧基或苄氧基）哌啶精制到哌啶-3-酮骨架中。