tert-butyl (S)-2-methyl-2-phenylpyrrolidine-1-carboxylate | 1364782-73-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: tert-butyl (S)-2-methyl-2-phenylpyrrolidine-1-carboxylate
• 英文别名: (S)-2-methyl-2-phenylpyrrolidine-1-carboxylic acid tert-butyl ester；tert-butyl (2S)-2-methyl-2-phenylpyrrolidine-1-carboxylate
• CAS: 1364782-73-9
• 化学式: C₁₆H₂₃NO₂
• 分子量: 261.364
• InChiKey: BHKCKEBYRZVJLX-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  (R)-tert-butyl 3-hydroxypropyl(1-phenylethyl)carbamate 在 草酰氯 、 Co(3,5-Di^tBu-Ibu-Phyrin) 、 caesium carbonate 、 二甲基亚砜 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 25.17h， 生成 tert-butyl (R)-2-methyl-2-phenylpyrrolidine-1-carboxylate 、 tert-butyl (S)-2-methyl-2-phenylpyrrolidine-1-carboxylate
  参考文献：
  名称：

  通过金属自由基 C-H 烷基化构建五元环结构的对映选择性自由基环化

  摘要：

  自由基环化代表了构建环状结构的强大策略。传统的自由基环化以自由基加成为关键步骤，需要使用不饱和底物。在金属自由基催化概念的指导下，通过开发基于Co(II)的系统，展示了一种可以使用饱和CH底物的不同自由基环化模式，该系统用于催化活化脂肪族重氮化合物，以实现各种C(sp3)的对映选择性自由基烷基化)-H键。它可以有效构建手性吡咯烷和其他有价值的五元环状化合物。这种自由基环化的替代策略提供了一种新的逆合成范例，通过 CH 和 C=O 元素的结合形成 CC 键，从容易获得的开链醛制备五元环状分子。

  DOI：

  10.1021/jacs.8b01662

文献信息

• An Experimental and in Situ IR Spectroscopic Study of the Lithiation–Substitution of <i>N</i>-Boc-2-phenylpyrrolidine and -piperidine: Controlling the Formation of Quaternary Stereocenters
  作者：Nadeem S. Sheikh、Daniele Leonori、Graeme Barker、James D. Firth、Kevin R. Campos、Anthony J. H. M. Meijer、Peter O’Brien、Iain Coldham

  DOI：10.1021/ja211398b

  日期：2012.3.21

  enantioselective synthesis of 2-substituted 2-phenylpyrrolidines and -piperidines, an important class of pharmaceutically relevant compounds that contain a quaternary stereocenter, has been developed. The approach involves lithiation-substitution of enantioenriched N-Boc-2-phenylpyrrolidine or -piperidine (prepared by asymmetric Negishi arylation or catalytic asymmetric reduction, respectively). The combined use

  已经开发了 2-取代的 2-苯基吡咯烷和 β-哌啶的一般和对映选择性合成，这是一类重要的含有季立体中心的药学相关化合物。该方法涉及对映体富集的 N-Boc-2-苯基吡咯烷或 -哌啶（分别通过不对称 Negishi 芳基化或催化不对称还原制备）的锂化取代。合成实验和原位红外光谱监测的结合使用可以确定最佳锂化条件：n-BuLi 在 THF 中在 -50°C 下保持 5-30 分钟。使用原位红外光谱监测锂化表明，叔丁氧羰基 (Boc) 基团在 2-锂化吡咯烷中的旋转比在 2-锂化哌啶中慢；N-Boc-2-苯基吡咯烷在-78°C 的锂化取代率低可归因于这种缓慢旋转。对于 N-Boc-2-苯基吡咯烷和 -哌啶，使用密度泛函理论计算和变温 (1) H NMR 光谱确定 Boc 基团的旋转障碍。对于吡咯烷，发现 Boc 基团旋转的半衰期 (t(1/2)) 在 -78°C 下为 ~10 小时，在 -50°C
• Synthetic Applications and Inversion Dynamics of Configurationally Stable 2-Lithio-2-arylpyrrolidines and -piperidines
  作者：Timothy K. Beng、Jin Sun Woo、Robert E. Gawley

  DOI：10.1021/ja306276w

  日期：2012.9.12

  In diethyl ether, N-Boc-2-lithio-2-arylpiperidines have been found to be configurationally stable at -80 degrees C, whereas N-Boc-2-lithio-2-arylpyrrolidines are configurationally stable at -60 degrees C. Several tertiary benzylic carbanions derived from enantioenriched 2-aryl heterocycles have been successfully alkylated or acylated with little to no loss of enantiopurity. The scope of the reactions has been explored. The enantiomerization dynamics of N-Boc-2-lithio-2-phenylpyrrolidine and N-Boc-2-lithio-2-phenylpiperidine have been studied in the presence of different solvents and achiral ligands.
• SYNTHESIS OF ACYCLIC AND CYCLIC AMINES USING IRON-CATALYZED NITRENE GROUP TRANSFER
  申请人：President and Fellows of Harvard College

  公开号：US20170072390A1

  公开（公告）日：2017-03-16

  The present invention provides novel synthetic methods for making acyclic secondary amines by reacting an azide with a compound bearing one or more C—H groups, catalyzed by a Fe II -dipyrromethene complex. The acyclic secondary amines are thought to be formed through an intermolecular nitrene transfer. Also provided herein are methods of synthesizing protected (e.g., Boc- or Fmoc-protected) cyclic secondary amines (e.g., 5-, 6-, and 7-membered cyclic secondary amines) by reacting an azide that bears one or more C—H groups, catalyzed by a Fe II -dipyrromethene complex. The protected cyclic secondary amines are thought to be formed through an intramolecular nitrene transfer and may be subsequently deprotected to yield cyclic secondary amines.