trans-4-(methoxycarbonyl)-5-(chlorodifluoromethyl)-5-phenyl-2-oxazoline

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: trans-4-(methoxycarbonyl)-5-(chlorodifluoromethyl)-5-phenyl-2-oxazoline
• 英文别名: methyl (4S,5S)-5-[chloro(difluoro)methyl]-5-phenyl-4H-1,3-oxazole-4-carboxylate
• 化学式: C₁₂H₁₀ClF₂NO₃
• 分子量: 289.666
• InChiKey: UJYXSISLOQZMJP-KOLCDFICSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  47.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  trans-4-(methoxycarbonyl)-5-(chlorodifluoromethyl)-5-phenyl-2-oxazoline 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 以91%的产率得到(2R*,3R*)-methyl N-formyl-3-(chlorodifluoromethyl)-3-phenylserinate
  参考文献：
  名称：

  Transition Metal/Base-Catalyzed Aldol Reactions of Isocyanoacetic Acid Derivatives with Prochiral Ketones, a Straightforward Approach to Stereochemically Defined β,β-Disubstituted-β-hydroxy-α-amino Acids.¹ Scope and Limitations

  摘要：

  A systematic study of the transition metal/base-catalyzed aldol reactions of methyl isocyanoacetate with a wide range of prochiral ketones, giving rise to the 4-(methoxycarbonyl)-5,5-disubstituted-2-oxazolines, has been made. The diastereoselectivity of these reactions was found to be influenced by a mix of several factors, including steric characteristic of the substituents, nature of the catalyst, electrostatic, and electron donor-acceptor type interactions. The former factor, a stereochemical discrimination between the substituents at the ketone carbon, was shown to be the most pronounced in controlling of the stereochemical outcome, which could be markedly improved with a proper choice of the catalyst. In particular, for the reactions of methyl isocyanoacetate with polyhaloalkyl aryl(alkyl) ketones, high diastereoselectivity (80-98% de) was achieved, thus allowing for straightforward and generalized access to the corresponding (2R*,3R*)-beta,beta-disubstituted-beta-hydroxy-alpha-amino carboxylic acid.

  DOI：

  10.1021/jo9623402
• 作为产物：
  描述：

  一氯二氟苯乙酮 、 异腈基乙酸甲酯 在 三乙胺 、 copper(l) chloride 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 0.17h， 以92%的产率得到trans-4-(methoxycarbonyl)-5-(chlorodifluoromethyl)-5-phenyl-2-oxazoline
  参考文献：
  名称：

  Transition Metal/Base-Catalyzed Aldol Reactions of Isocyanoacetic Acid Derivatives with Prochiral Ketones, a Straightforward Approach to Stereochemically Defined β,β-Disubstituted-β-hydroxy-α-amino Acids.¹ Scope and Limitations

  摘要：

  A systematic study of the transition metal/base-catalyzed aldol reactions of methyl isocyanoacetate with a wide range of prochiral ketones, giving rise to the 4-(methoxycarbonyl)-5,5-disubstituted-2-oxazolines, has been made. The diastereoselectivity of these reactions was found to be influenced by a mix of several factors, including steric characteristic of the substituents, nature of the catalyst, electrostatic, and electron donor-acceptor type interactions. The former factor, a stereochemical discrimination between the substituents at the ketone carbon, was shown to be the most pronounced in controlling of the stereochemical outcome, which could be markedly improved with a proper choice of the catalyst. In particular, for the reactions of methyl isocyanoacetate with polyhaloalkyl aryl(alkyl) ketones, high diastereoselectivity (80-98% de) was achieved, thus allowing for straightforward and generalized access to the corresponding (2R*,3R*)-beta,beta-disubstituted-beta-hydroxy-alpha-amino carboxylic acid.

  DOI：

  10.1021/jo9623402

文献信息

• Highly diastereoselective aldol reaction of fluoroalkyl aryl ketones with methyl isocyanoacetate catalyzed by silver(I)/triethylamine
  作者：Vadim A. Soloshonok、Tamio Hayashi、Kohki Ishikawa、Nobuya Nagashima

  DOI：10.1016/s0040-4039(00)79964-3

  日期：1994.2

  Transition metal-catalyzed aldol reaction of aryl fluoroalkyl ketones with methyl isocyanoacetate was found to proceed with high diastereoselectivity that is in sharp contrast to the very poor diastereoselectivity in the similar reaction of nonfluorinated ketones. The superiority of AgClO4/NEt3 as a homogeneous catalyst (1 mol %) for these reactions was disclosed.

  发现芳基氟代烷基酮与异氰基乙酸甲酯的过渡金属催化的羟醛反应以高的非对映选择性进行，这与非氟化酮的类似反应中非常差的非对映选择性形成鲜明对比。公开了AgClO 4 / NEt 3作为均相催化剂（1摩尔％）对于这些反应的优越性。