<3(2S,3S),4S>-4-Benzyl-3-<3-(2,4-difluorophenyl)-3,4-epoxy-2-methyl-1-oxobutyl>-2-oxazolidinone

• 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: <3(2S,3S),4S>-4-Benzyl-3-<3-(2,4-difluorophenyl)-3,4-epoxy-2-methyl-1-oxobutyl>-2-oxazolidinone
• 英文别名: (4S)-4-benzyl-3-[(2S)-2-[(2S)-2-(2,4-difluorophenyl)oxiran-2-yl]propanoyl]-1,3-oxazolidin-2-one
• 化学式: C₂₁H₁₉F₂NO₄
• 分子量: 387.383
• InChiKey: SJRVUCOOQMMMJY-QTPGKHNVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  <3(2S,3S),4S>-4-Benzyl-3-<3-(2,4-difluorophenyl)-3,4-epoxy-2-methyl-1-oxobutyl>-2-oxazolidinone 在 lithium hydroxide 、 双氧水 作用下， 生成 (2S,3S)-3-(2,4-Difluorophenyl)-3,4-epoxy-2-methylbutanoic acid
  参考文献：
  名称：

  Aldol Condensation of Evans Chiral Enolates with Acetophenones. Its Application to the Stereoselective Synthesis of Homochiral Antifungal Agents

  摘要：

  The results of the aldol condensation of Evans chiral imide enolates with a series of acetophenones are reported. Activated acetophenones, such as 2,4-difluoroacetophenone, alpha-chloroacetophenone, and alpha-chloro- and alpha-bromo-2,4-difluoroacetophenone, reacted with the lithium enolate of 5 with good levels of enolate facial diastereoselectivity toward the (2R)-isomers (> 10:1) but with low anti:syn selectivity (ca. 3:2). Sodium and potassium enolates of 5 were also tested. The nature of the solvent influenced the degree of diastereofacial biases. Less activated ketones, such as acetophenone, reacted only to a ca. 50% extent without facial or anti:syn stereoselectivities. Chairlike pericyclic transition states are believed to govern the reaction. When alpha-bromoacetophenones were used, longer reaction times and higher temperatures resulted in the selective formation of the S-2 epoxide (syn-(2R,3R), 11) with good levels of selectivity. Equilibration studies performed in THF with the corresponding metal aldolates generated in situ by deprotonation of the aldol adducts indicated that an aldol/retroaldol process was first established followed by a slower formation of the epoxide. Stereoselection is thought to originate by a faster oxirane formation of the syn bromohydrins as compared to the anti due to steric interactions between the alpha-group and the leaving bromide. Optimum retroaldol-epoxide formation rates were obtained using the sodium enolate in ether at -78 degrees C. Under these conditions the S-1:S-2:A(1)A(2) ratio of epoxides was 6:83:10:0.3 and the major isomer was isolated by recrystallization in 79% yield. An improved synthesis of amino alcohol 3, an advanced intermediate in the preparation of orally active antifungal agents, using a tandem of this new ketone-aldol technology and a Curtius rearrangement, is reported. The new sequence proceeds with an overall yield of 53% and does not require chromatographic purifications.

  DOI：

  10.1021/jo00115a014
• 作为产物：
  描述：

  2-溴-2',4'-二氟苯乙酮 、 (S)-4-苄基-3-丙酰基-2-噁唑烷酮 在 sodium hexamethyldisilazane 作用下， 以 乙醚 为溶剂， 生成 <3(2S,3R),4S>-4-Benzyl-3-<3-(2,4-difluorophenyl)-3,4-epoxy-2-methyl-1-oxobutyl>-2-oxazolidinone 、 <3(2R,3R),4S>-4-Benzyl-3-<3-(2,4-difluorophenyl)-3,4-epoxy-2-methyl-1-oxobutyl>-2-oxazolidinone 、 <3(2S,3S),4S>-4-Benzyl-3-<3-(2,4-difluorophenyl)-3,4-epoxy-2-methyl-1-oxobutyl>-2-oxazolidinone 、 <3(2R,3S),4S>-4-Benzyl-3-<3-(2,4-difluorophenyl)-3,4-epoxy-2-methyl-1-oxobutyl>-2-oxazolidinone
  参考文献：
  名称：

  Aldol Condensation of Evans Chiral Enolates with Acetophenones. Its Application to the Stereoselective Synthesis of Homochiral Antifungal Agents

  摘要：

  The results of the aldol condensation of Evans chiral imide enolates with a series of acetophenones are reported. Activated acetophenones, such as 2,4-difluoroacetophenone, alpha-chloroacetophenone, and alpha-chloro- and alpha-bromo-2,4-difluoroacetophenone, reacted with the lithium enolate of 5 with good levels of enolate facial diastereoselectivity toward the (2R)-isomers (> 10:1) but with low anti:syn selectivity (ca. 3:2). Sodium and potassium enolates of 5 were also tested. The nature of the solvent influenced the degree of diastereofacial biases. Less activated ketones, such as acetophenone, reacted only to a ca. 50% extent without facial or anti:syn stereoselectivities. Chairlike pericyclic transition states are believed to govern the reaction. When alpha-bromoacetophenones were used, longer reaction times and higher temperatures resulted in the selective formation of the S-2 epoxide (syn-(2R,3R), 11) with good levels of selectivity. Equilibration studies performed in THF with the corresponding metal aldolates generated in situ by deprotonation of the aldol adducts indicated that an aldol/retroaldol process was first established followed by a slower formation of the epoxide. Stereoselection is thought to originate by a faster oxirane formation of the syn bromohydrins as compared to the anti due to steric interactions between the alpha-group and the leaving bromide. Optimum retroaldol-epoxide formation rates were obtained using the sodium enolate in ether at -78 degrees C. Under these conditions the S-1:S-2:A(1)A(2) ratio of epoxides was 6:83:10:0.3 and the major isomer was isolated by recrystallization in 79% yield. An improved synthesis of amino alcohol 3, an advanced intermediate in the preparation of orally active antifungal agents, using a tandem of this new ketone-aldol technology and a Curtius rearrangement, is reported. The new sequence proceeds with an overall yield of 53% and does not require chromatographic purifications.

  DOI：

  10.1021/jo00115a014

文献信息

• Aldol Condensation of Evans Chiral Enolates with Acetophenones. Its Application to the Stereoselective Synthesis of Homochiral Antifungal Agents
  作者：Javier Bartroli、Enric Turmo、Jordi Belloc、Javier Forn

  DOI：10.1021/jo00115a014

  日期：1995.5

  The results of the aldol condensation of Evans chiral imide enolates with a series of acetophenones are reported. Activated acetophenones, such as 2,4-difluoroacetophenone, alpha-chloroacetophenone, and alpha-chloro- and alpha-bromo-2,4-difluoroacetophenone, reacted with the lithium enolate of 5 with good levels of enolate facial diastereoselectivity toward the (2R)-isomers (> 10:1) but with low anti:syn selectivity (ca. 3:2). Sodium and potassium enolates of 5 were also tested. The nature of the solvent influenced the degree of diastereofacial biases. Less activated ketones, such as acetophenone, reacted only to a ca. 50% extent without facial or anti:syn stereoselectivities. Chairlike pericyclic transition states are believed to govern the reaction. When alpha-bromoacetophenones were used, longer reaction times and higher temperatures resulted in the selective formation of the S-2 epoxide (syn-(2R,3R), 11) with good levels of selectivity. Equilibration studies performed in THF with the corresponding metal aldolates generated in situ by deprotonation of the aldol adducts indicated that an aldol/retroaldol process was first established followed by a slower formation of the epoxide. Stereoselection is thought to originate by a faster oxirane formation of the syn bromohydrins as compared to the anti due to steric interactions between the alpha-group and the leaving bromide. Optimum retroaldol-epoxide formation rates were obtained using the sodium enolate in ether at -78 degrees C. Under these conditions the S-1:S-2:A(1)A(2) ratio of epoxides was 6:83:10:0.3 and the major isomer was isolated by recrystallization in 79% yield. An improved synthesis of amino alcohol 3, an advanced intermediate in the preparation of orally active antifungal agents, using a tandem of this new ketone-aldol technology and a Curtius rearrangement, is reported. The new sequence proceeds with an overall yield of 53% and does not require chromatographic purifications.