2-((2S,4S,5R)-3,4-Dimethyl-5-phenyl-oxazolidin-2-yl)-N,N-diethyl-benzamide

• 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: 2-((2S,4S,5R)-3,4-Dimethyl-5-phenyl-oxazolidin-2-yl)-N,N-diethyl-benzamide
• 英文别名: 2-[(2S,4S,5R)-3,4-dimethyl-5-phenyl-1,3-oxazolidin-2-yl]-N,N-diethylbenzamide
• 化学式: C₂₂H₂₈N₂O₂
• 分子量: 352.477
• InChiKey: CCHMCSCJKMYTPV-BUKVSMQUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-((2S,4S,5R)-3,4-Dimethyl-5-phenyl-oxazolidin-2-yl)-N,N-diethyl-benzamide 、 碘甲烷 在 四甲基乙二胺 、 仲丁基锂 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以57.7%的产率得到(2'S,4'S,5'R)-N,N-diethyl-2-[3,4-dimethyl-5-phenyl-1,3-oxazolan-2-yl]-6-methylbenzamide
  参考文献：
  名称：

  Conformational preference in aromatic amides bearing chiral ortho substituents: its origin and application to relayed stereocontrol

  摘要：

  具有立体中心的第三芳香酰胺在酰胺基团邻位可能采用两种不同的非对映异构体构象，这两种构象在环境温度下在核磁共振（NMR）时间尺度上缓慢互变，因此可通过NMR检测到。某些类型的立体中心，特别是亚磺酸盐、源自麻黄碱的噁唑啉和源自脯氨酸的咪唑啉，显著影响两种构象的分布。我们提出了一个模型，并通过分子力学计算支持该模型，合理化了根据控制中心的立体和电子特性所获得的构象选择性的方向和大小。对构象的控制可以通过将偏好的构象捕获为旋转异构体，或通过利用它来传递关于控制中心立体化学的信息来实现。

  DOI：

  10.1039/b514557k
• 作为产物：
  描述：

  麻黄碱 、 N,N-diethyl-2-formylbenzamide 以 甲苯 为溶剂， 反应 16.0h， 以34%的产率得到2-((2S,4S,5R)-3,4-Dimethyl-5-phenyl-oxazolidin-2-yl)-N,N-diethyl-benzamide
  参考文献：
  名称：

  使用脯氨酸衍生的咪唑啉和麻黄碱衍生的恶唑烷类化合物动态拆分阻转异构酰胺

  摘要：

  阻转异构的叔2-甲酰基萘酰胺或2-甲酰基苯甲酰胺与一些手性二胺和氨基醇的缩合通过动态拆分过程导致带有手性咪唑烷或恶唑烷的叔酰胺的单一阻转异构体。新杂环的水解与起始醛的动态热力学拆分竞争，并且快速还原可分离出对映异构体富集形式的带有2-羟甲基取代基的阻转异构酰胺。提供了反应在热力学控制下的证据。

  DOI：

  10.1016/j.tet.2004.01.101

文献信息

• Dynamic resolution of atropisomeric amides using proline-derived imidazolines and ephedrine-derived oxazolidines
  作者：Jonathan Clayden、Lai Wah Lai、Madeleine Helliwell

  DOI：10.1016/j.tet.2004.01.101

  日期：2004.5

  some chiral diamines and amino alcohols leads, via a dynamic resolution process, to single atropisomers of tertiary amides bearing chiral imidazolidines or oxazolidines. Hydrolysis of the new heterocycle competes a dynamic thermodynamic resolution of the starting aldehyde, and rapid reduction allows the isolation of atropisomeric amides bearing 2-hydroxymethyl substituents in enantiomerically enriched

  阻转异构的叔2-甲酰基萘酰胺或2-甲酰基苯甲酰胺与一些手性二胺和氨基醇的缩合通过动态拆分过程导致带有手性咪唑烷或恶唑烷的叔酰胺的单一阻转异构体。新杂环的水解与起始醛的动态热力学拆分竞争，并且快速还原可分离出对映异构体富集形式的带有2-羟甲基取代基的阻转异构酰胺。提供了反应在热力学控制下的证据。
• Using amide conformation to ‘project’ the stereochemistry of an (−)-ephedrine-derived oxazolidine: a pair of pseudoenantiomeric chiral amido-phosphine ligands
  作者：Jonathan Clayden、Lai Wah Lai、Madeleine Helliwell

  DOI：10.1016/s0957-4166(01)00110-0

  日期：2001.4

  Protection of a tertiary 2-formylbenzamide as an (-)-ephedrine-derived oxazolidine both Fords the amide's stereogenic Ar-CO axis to adopt one of two possible diastereoisomeric conformations and protects the formyl group from attack during amide ortho-lithiation. By functionalising the amide in the 6-position, reactive sites (such as -CHO, -SR, -PR2 groups) may be introduced which fall under the stereochemical influence, relayed by the amide: of the (-)-ephedrine-derived oxazolidine. This 'projection' of stereochemistry is exemplified by a pair of amido-phosphines. members of the first ever class of non-biaryl atropisomeric ligands, which are made functionally pseudoenantiomeric by the intervention of either one or two amide groups between the (-)-ephedrine-derived oxazolidine and the PPh2 group. The pseudoenantiomeric amido-phosphines promote the palladium-catalysed asymmetric allylation of dimethyl malonate in 82 and -53% e.e., respectively. (C) 2001 Published by Elsevier Science Ltd.
• (−)-Ephedrine as an auxiliary for the asymmetric synthesis of atropisomeric amides by dynamic resolution under thermodynamic control
  作者：Jonathan Clayden、Lai Wah Lai

  DOI：10.1016/s0040-4039(01)00416-6

  日期：2001.4

  N,N-Dialkyl-2-formylbenzamides and N,N-dialkyl-2-formyl-1-naphthamides condense with (-)-ephedrine in refluxing toluene to give oxazolidines both as single diastereoisomers with respect to the new stereogenic centre and as single conformers with respect to the slowly-rotating Ar-CONR2 bond. In the naphthamide series, removal of the ephedrine auxiliary by hydrolysis returns the starting aldehyde (isolated by reduction to the more stable alcohol) in enantiomerically enriched form (up to 94% ee). Overall, the two-step sequence amounts to a dynamic resolution under thermodynamic control. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Conformational preference in aromatic amides bearing chiral ortho substituents: its origin and application to relayed stereocontrol
  作者：Mark S. Betson、Jonathan Clayden、Madeleine Helliwell、Paul Johnson、Lai Wah Lai、Jennifer H. Pink、Christopher C. Stimson、Neoclis Vassiliou、Neil Westlund、Samreen A. Yasin、Latifa H. Youssef

  DOI：10.1039/b514557k

  日期：——

  Tertiary aromatic amides bearing stereogenic centres ortho to the amide group may adopt two diastereoisomeric conformations which interconvert slowly on the NMR timescale at ambient temperature, and are therefore detectable by NMR. Certain classes of stereogenic centre—particularly sulfoxides, ephedrine-derived oxazolidines, and proline-derived imidazolidines—strongly bias the population of the two conformers. We propose a model, supported by molecular mechanics calculations, which rationalises the sense and magnitude of the conformational selectivity attained in terms of the steric and electronic properties of the controlling centre. The control over conformation may be exploited either by trapping the favoured conformer as an atropisomer, or by using it to relay information about the stereochemistry of the controlling centre.

  具有立体中心的第三芳香酰胺在酰胺基团邻位可能采用两种不同的非对映异构体构象，这两种构象在环境温度下在核磁共振（NMR）时间尺度上缓慢互变，因此可通过NMR检测到。某些类型的立体中心，特别是亚磺酸盐、源自麻黄碱的噁唑啉和源自脯氨酸的咪唑啉，显著影响两种构象的分布。我们提出了一个模型，并通过分子力学计算支持该模型，合理化了根据控制中心的立体和电子特性所获得的构象选择性的方向和大小。对构象的控制可以通过将偏好的构象捕获为旋转异构体，或通过利用它来传递关于控制中心立体化学的信息来实现。