(2R,3S,6S)-methyl 6-((R)-bromo(phenyl)methyl)-2,6-dimethyl-4-((4-nitrophenyl)sulfonyl)morpholine-3-carboxylate | 1421070-67-8

• 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: (2R,3S,6S)-methyl 6-((R)-bromo(phenyl)methyl)-2,6-dimethyl-4-((4-nitrophenyl)sulfonyl)morpholine-3-carboxylate
• 英文别名: methyl (2R,3S,6S)-6-[(R)-bromo(phenyl)methyl]-2,6-dimethyl-4-(4-nitrophenyl)sulfonylmorpholine-3-carboxylate
• CAS: 1421070-67-8
• 化学式: C₂₁H₂₃BrN₂O₇S
• 分子量: 527.393
• InChiKey: OYRHJDIGYDLVTI-WBHLOVLFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  127
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (2S,3R)-methyl 3-hydroxy-2-(N-((Z)-2-methyl-3-phenylallyl)-4-nitrophenylsulfonamido)butanoate 在 N-溴代丁二酰亚胺(NBS) 、 D(+)-10-樟脑磺酸 作用下， 以 四氢呋喃 为溶剂， 反应 17.0h， 以39%的产率得到(2R,3S,6R,7S)-methyl 6-bromo-2,6-dimethyl-4-((4-nitrophenyl)sulfonyl)-7-phenyl-1,4-oxazepane-3-carboxylate
  参考文献：
  名称：

  Stereo- and Regioselective Synthesis of Polysubstituted Chiral 1,4-Oxazepanes

  摘要：

  The number of cyclic molecular scaffolds available to medicinal chemists remains limited, and simple structures such as oxazepanes are still made using multistep procedures, including a number of protection/deprotection steps and purifications. We report herein an expedient and efficient synthesis of chiral polysubstituted oxazepanes. The developed method relies on a regio- and stereoselective 7-endo cyclization through haloetherification. Mechanistic studies using a combination of computations and experiments confirmed the expected role of the asymmetry of the chiral bromonium intermediate on the haloetherification regioselectivity. Computations also suggested that the bromonium intermediate is formed with no transition state; hence, the stereoselectivity is controlled primarily by the conformation of the substrate. Applied to a set of 16 substrates, tetra- and pentasubstituted oxazepanes were prepared with good yields and moderate to excellent regio- and stereoselectivities.

  DOI：

  10.1021/jo3021715

文献信息

• Stereo- and Regioselective Synthesis of Polysubstituted Chiral 1,4-Oxazepanes
  作者：Michelle Bezanson、Joshua Pottel、Rana Bilbeisi、Sylvestre Toumieux、Mickaël Cueto、Nicolas Moitessier

  DOI：10.1021/jo3021715

  日期：2013.2.1

  The number of cyclic molecular scaffolds available to medicinal chemists remains limited, and simple structures such as oxazepanes are still made using multistep procedures, including a number of protection/deprotection steps and purifications. We report herein an expedient and efficient synthesis of chiral polysubstituted oxazepanes. The developed method relies on a regio- and stereoselective 7-endo cyclization through haloetherification. Mechanistic studies using a combination of computations and experiments confirmed the expected role of the asymmetry of the chiral bromonium intermediate on the haloetherification regioselectivity. Computations also suggested that the bromonium intermediate is formed with no transition state; hence, the stereoselectivity is controlled primarily by the conformation of the substrate. Applied to a set of 16 substrates, tetra- and pentasubstituted oxazepanes were prepared with good yields and moderate to excellent regio- and stereoselectivities.