(R)-[(2S)-1-benzylpyrrolidin-2-yl](phenyl)methanol | 220058-21-9

• 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: (R)-[(2S)-1-benzylpyrrolidin-2-yl](phenyl)methanol
• 英文别名: (R)-[(2S)-1-benzylpyrrolidin-2-yl]-phenylmethanol
• CAS: 220058-21-9
• 化学式: C₁₈H₂₁NO
• 分子量: 267.371
• InChiKey: HULBHXXRMFVTCL-ZWKOTPCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-[(2S)-1-benzylpyrrolidin-2-yl](phenyl)methanol 在 sodium azide 、 palladium 10% on activated carbon 、 氢气 、 甲基磺酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 55.0 ℃ 、413.7 kPa 条件下， 反应 58.0h， 生成 1-{(R)-[(S)-1-benzylpyrrolidin-2-yl](phenyl)methyl}-3-phenylthiourea
  参考文献：
  名称：

  Synthesis of Versatile Bifunctional Derivatives of Chiral Diamines Obtained through Anchimerically Assisted Nucleophilic Substitution Reactions on Diastereomeric Phenylprolinols

  摘要：

  Diastereomeric [(S)-1-benzylpyrrolidin-2-yl]-(R)-[(phenyl)methanamine] and [(S)-1-benzylpyrrolidin-2-yl]-(S)-[(phenyl)methanamine], were synthesized by selective internal backside nucleophilic substitution of the corresponding activated phenylprolinols. X-Ray diffraction structures of crystalline acetamide derivatives confirmed the anticipated stereochemistry for a S(N)ib reaction mechanism. In order to apply this reaction to the synthesis of bifunctional analogs, a series of fragments such as a thiourea moiety and sulfonamide functions were introduced for the functionalization of the primary amino group in the substrate, obtaining more stable and potentially useful derivatives.

  DOI：

  10.3987/com-12-s(n)82
• 作为产物：
  描述：

  N-benzyl-(S)-proline methyl ester 在 lithium aluminium tetrahydride 、 草酰氯 、 magnesium 、 二甲基亚砜 、 lithium bromide 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 16.33h， 生成 (R)-[(2S)-1-benzylpyrrolidin-2-yl](phenyl)methanol
  参考文献：
  名称：

  Synthesis of Versatile Bifunctional Derivatives of Chiral Diamines Obtained through Anchimerically Assisted Nucleophilic Substitution Reactions on Diastereomeric Phenylprolinols

  摘要：

  Diastereomeric [(S)-1-benzylpyrrolidin-2-yl]-(R)-[(phenyl)methanamine] and [(S)-1-benzylpyrrolidin-2-yl]-(S)-[(phenyl)methanamine], were synthesized by selective internal backside nucleophilic substitution of the corresponding activated phenylprolinols. X-Ray diffraction structures of crystalline acetamide derivatives confirmed the anticipated stereochemistry for a S(N)ib reaction mechanism. In order to apply this reaction to the synthesis of bifunctional analogs, a series of fragments such as a thiourea moiety and sulfonamide functions were introduced for the functionalization of the primary amino group in the substrate, obtaining more stable and potentially useful derivatives.

  DOI：

  10.3987/com-12-s(n)82

文献信息

• Enantioselective Ring Expansion of Prolinols: An Efficient and Short Synthesis of 2-Phenylpiperidin-3-ol Derivatives and 3-Hydroxypipecolic Acids
  作者：Domingo Gomez Pardo、Janine Cossy、Anne Cochi、Benjamin Burger、Cristina Navarro、Yang Zhao、Theodore Cohen

  DOI：10.1055/s-0029-1217568

  日期：2009.8

  A very short route to 2-phenylpiperidin-3-ol derivatives and 3-hydroxypipecolic acids is described. The approach uses two key steps: a one-pot reduction/Grignard addition sequence applied to alkyl proline esters and a ring expansion applied to the corresponding prolinols.

  描述了一种非常简短的方法来合成2-苯基哌啶-3-醇衍生物和3-羟基皮克酸。该方法采用两个关键步骤：针对烷基脯氨酸酯的一锅还原/格氏试剂加成反应序列，以及对相应脯氨醇的环扩展反应。
• Synthesis of Diastereomeric Pyrrolidine Sulfamides via Anchimerically Assisted Nucleophilic Substitution Reactions
  作者：Jorge Vargas-Caporali、Arie van der Lee、Georges Dewynter、Eusebio Juaristi

  DOI：10.2174/1570178615666180110162202

  日期：2018.4.12

  type of diastereomeric amino alcohols to the above-mentioned nucleophile usually leads to the formation of piperidines via ring expansion, either through classical nucleophilic substitution or the Mitsunobu version, only the pyrrolidine derivatives were generated with retention of configuration on the exocyclic stereocenter, owing to the neighboring group participation (internal backside nucleophilic

  在开发方便的合成路线的关键步骤中，Mitsunobu反应用于从（R）-或（S）-[（S）-1-苄基吡咯烷丁-2-基]（）对映选择性制备吡咯烷-磺酰胺配体苯基）甲醇，并使用叔丁基吡咯烷-1--1-基磺酰基氨基甲酸酯作为非常规亲核源。尽管有充分的文献证明，这类非对映体氨基醇暴露于上述亲核试剂通常会导致环扩环形成哌啶，无论是通过经典亲核取代还是Mitsunobu版本，只有吡咯烷衍生物得以保留由于邻近基团的参与（内部背面亲核取代，SNib），在环外立体中心的构型改变。
• Enantioselective synthesis of 2,3-disubstituted piperidines from (S)-methylpyroglutamate
  作者：Olivier Calvez、Angèle Chiaroni、Nicole Langlois

  DOI：10.1016/s0040-4039(98)02190-x

  日期：1998.12

  N-methoxy-N-methylamide derived from (S)-methylpyroglutamate was prepared in good yield and allowed the addition of Grignard reagents. Erythro (2S)-1-benzyl-2-hydroxybenzyl pyrrolidine obtained by this way was converted into (2S,3R)-1-benzyl-3-hydroxy-2-phenylpiperidine and its chloro analog.

  以高收率制备衍生自（S）-甲基焦谷氨酸的N-甲氧基-N-甲基酰胺，并加入格氏试剂。将由此获得的赤型（2S）-1-苄基-2-羟基苄基吡咯烷转化为（2S，3R）-1-苄基-3-羟基-2-苯基哌啶及其氯代类似物。
• Synthesis of a variety of optically active hydroxylated heterocyclic compounds using epoxide hydrolase technology
  作者：Daniel P. Pienaar、Robin K. Mitra、Thomas I. van Deventer、Adriana L. Botes

  DOI：10.1016/j.tetlet.2008.08.097

  日期：2008.11

  Novel epoxide hydrolases in Yarrowia lipolytica have been shown to hydrolyse a variety of functionalised epoxides with good to excellent stereoselectivity and at high volumetric productivities. Individual biotransformation products have been converted into optically active (R)-(tetrahydrofun-2-yl)methanol (6), (S)-N-benzyl-3-hydroxypyrrolidine (7), (S)-3-hydroxytetrahydrothiophene (8), (S)-N-benzyl-3-acetoxypiperidine (10), (S)-3-hydroxytetrahydrofuran (16) and (R)-[(S)-N-benzylpyrrolidin-2-yl](phenyl)-methanol (20). (C) 2008 Elsevier Ltd. All rights reserved.
• Enantioselective addition of dialkylzinc reagents to N-(diphenylphosphinoyl)imines catalyzed by β-aminoalcohols with the prolinol skeleton
  作者：Raquel Almansa、David Guijarro、Miguel Yus

  DOI：10.1016/j.tetasy.2007.11.006

  日期：2007.11

  Several beta-aminoalcohols with the prolinol framework are shown to be very efficient catalysts for the enantioselective addition of dialkylzinc reagents to N-(diphenylphosphinoyl)imines. The use of 0.5 equiv of the catalyst leads to the expected addition products in good yields and with ee up to 94% in a reaction time of only 4 It at room temperature. This ee is the highest value reported so far using 0.5 equiv of an aminoalcohol as a promoter. High enantioselectivities are obtained in the addition of dialkylzincs to both aromatic and aliphatic imines. The amount of the catalyst can be reduced to 0.25 equiv with a slight decrease in the ee. A very interesting effect of the addition rate and temperature on the enantioselectivity was also observed. (c) 2007 Elsevier Ltd. All rights reserved.