<3(2R,3R),4S>-4-Benzyl-3-<4-chloro-3-(2,4-difluorophenyl)-3-hydroxy-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(2R,3R),4S>-4-Benzyl-3-<4-chloro-3-(2,4-difluorophenyl)-3-hydroxy-2-methyl-1-oxobutyl>-2-oxazolidinone
• 英文别名: (4S)-4-benzyl-3-[(2R,3R)-4-chloro-3-(2,4-difluorophenyl)-3-hydroxy-2-methyl-1-oxobutyl]-1,3-oxazolidin-2-one；(4S)-3-[(2R,3R)-4-Chloro-3-(2,4-difluorophenyl)-3-hydroxy-2-methyl-1-oxobutyl]-4-(phenylmethyl)-2-oxazolidinone；(4S)-4-benzyl-3-[(2R,3R)-4-chloro-3-(2,4-difluorophenyl)-3-hydroxy-2-methylbutanoyl]-1,3-oxazolidin-2-one
• 化学式: C₂₁H₂₀ClF₂NO₄
• 分子量: 423.844
• InChiKey: VWEREKJCRSAXPE-UYTHQXMGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-氯-2',4'-二氟苯乙酮 、 (S)-4-苄基-3-丙酰基-2-噁唑烷酮 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 <3(2S,3S),4S>-4-Benzyl-3-<4-chloro-3-(2,4-difluorophenyl)-3-hydroxy-2-methyl-1-oxobutyl>-2-oxazolidinone 、 <3(2R,3S),4S>-4-Benzyl-3-<4-chloro-3-(2,4-difluorophenyl)-3-hydroxy-2-methyl-1-oxobutyl>-2-oxazolidinone 、 <3(2S,3R),4S>-4-Benzyl-3-<4-chloro-3-(2,4-difluorophenyl)-3-hydroxy-2-methyl-1-oxobutyl>-2-oxazolidinone 、 <3(2R,3R),4S>-4-Benzyl-3-<4-chloro-3-(2,4-difluorophenyl)-3-hydroxy-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

• Asymmetric zinc-Reformatsky reaction of Evans chiral imide with acetophenones and its application to the stereoselective synthesis of triazole antifungal agents
  作者：Luo-Ting Yu、Meng-Tsung Ho、Ching-Yao Chang、Teng-Kuei Yang

  DOI：10.1016/j.tetasy.2007.03.015

  日期：2007.5

  Reformatsky-type reaction of Evans chiral imide with various acetophenones was studied. The chiral imido zinc enolate, which was formed through the metal–halogen exchange reaction of chiral α-bromopropionyl-2-oxazolidinones 2 with diethyl zinc under the catalysis of Ni(acac)2, performed the asymmetric zinc-Reformatsky reaction with activated α-haloacetophenones 3 to give the chiral β-hydroxyamide 4 in good

  研究了Evans手性酰亚胺与各种苯乙酮的Ni（acac）2催化ZnEt 2介导的不对称Reformatsky型反应。在Ni（acac）2的催化下，手性α-溴丙酰基-2-恶唑烷二酮2与二乙基锌的金属-卤素交换反应形成的手性亚氨基烯酸锌烯醇盐，通过活化的α-进行不对称的锌-Reformatsky反应。 haloacetophenones 3，得到手性β羟基酰胺4以良好的收率和高比例顺式- （2- [R，3 - [R）异构体（高达> 97％）。这种新的不对称合成技术提供了一种实用的方法，可以合成用于三唑类抗真菌剂（如伏立康唑，拉伏康唑，TAK-187和RO-0094815）的通用手性构件5。
• 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.