methyl (2S,5R,3Z)-5-[N-(tert-butoxycarbonyl)amino]-4-fluoro-2-(2-methylpropyl)-6-phenylhex-3-enoate

• 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: methyl (2S,5R,3Z)-5-[N-(tert-butoxycarbonyl)amino]-4-fluoro-2-(2-methylpropyl)-6-phenylhex-3-enoate
• 英文别名: methyl (Z,2S,5R)-4-fluoro-5-[(2-methylpropan-2-yl)oxycarbonylamino]-2-(2-methylpropyl)-6-phenylhex-3-enoate
• 化学式: C₂₂H₃₂FNO₄
• 分子量: 393.499
• InChiKey: VXUOEPUXZIVZSI-QEGJZFQBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  异丙基氯化镁 、 三甲基硅烷化重氮甲烷 、 (2R)-2-{(3R,1Z)-3-[N-(tert-butoxycarbonyl)amino]-2-fluoro-4-phenylbut-1-enyl}propano-3-lactone 在 copper(I) bromide dimethylsulfide complex 作用下， 以 四氢呋喃 、 乙醚 、 甲醇 、 正己烷 、 苯 为溶剂， 以66%的产率得到methyl (2S,5R,3Z)-5-[N-(tert-butoxycarbonyl)amino]-4-fluoro-2-(2-methylpropyl)-6-phenylhex-3-enoate
  参考文献：
  名称：

  SmI₂-Mediated Reduction of γ,γ-Difluoro-α,β-enoates with Application to the Synthesis of Functionalized (Z)-Fluoroalkene-Type Dipeptide Isosteres

  摘要：

  A samarium diiodide (SmI2)-mediated reduction of gamma,gamma-difluoro-alpha,beta-enoates (15, 29, and 34) was successfully applied to the synthesis of (Z)-fluoroalkene dipeptide isosteres (23, 30, and 35), which have served as potential dipeptide mimetics. Reduction of the gamma,gamma-difluoro-alpha,beta-enoates by SmI2 proceeded via successive two-electron transfers to form dienolate species which upon kinetically controlled trapping with t-BuOH yielded Xaa-Gly-type fluoroalkene isosteres exemplified by 23, 30, and 35. Replacement of the t-BuOH kinetic trapping agent with aldehydes or ketones provided access to a-substituted fluoroalkene isosteres (43 and 45) through aldol reactions of Sm-dienolates with the carbonyl compounds. Of particular note, the use of the SmI2-HCHO reagent system with chiral enoate 34 provided D-Phe-psi[(Z)-CF=CH]-D/L-Ser isosteres (45), which could be converted to enantiomerically pure isosteres (49-52) that bore a variety of side chain functionalities at the a-position. This was achieved by a sequence of manipulations consisting of beta-lactone formation followed by chromatographic separation and ring-opening with soft nucleophiles. Included in the present work is the first utilization of a Rh-catalyzed Reformatsky reaction of chiral imines for the stereoselective preparation of alpha,alpha-difluoro-beta-amino acid derivatives (28 and 33). The appropriate choice of reagents (carbonyl compounds for kinetic trapping or ring-opening nucleophiles and imines for Reformatsky reactions) allows the presented methodology to yield various fluoroalkene isosteres possessing a wide range of side chain functionalities.

  DOI：

  10.1021/jo035709d

文献信息

• SmI₂-Mediated Reduction of γ,γ-Difluoro-α,β-enoates with Application to the Synthesis of Functionalized (<i>Z</i>)-Fluoroalkene-Type Dipeptide Isosteres
  作者：Akira Otaka、Junko Watanabe、Akira Yukimasa、Yoshikazu Sasaki、Hideaki Watanabe、Takayoshi Kinoshita、Shinya Oishi、Hirokazu Tamamura、Nobutaka Fujii

  DOI：10.1021/jo035709d

  日期：2004.3.1

  A samarium diiodide (SmI2)-mediated reduction of gamma,gamma-difluoro-alpha,beta-enoates (15, 29, and 34) was successfully applied to the synthesis of (Z)-fluoroalkene dipeptide isosteres (23, 30, and 35), which have served as potential dipeptide mimetics. Reduction of the gamma,gamma-difluoro-alpha,beta-enoates by SmI2 proceeded via successive two-electron transfers to form dienolate species which upon kinetically controlled trapping with t-BuOH yielded Xaa-Gly-type fluoroalkene isosteres exemplified by 23, 30, and 35. Replacement of the t-BuOH kinetic trapping agent with aldehydes or ketones provided access to a-substituted fluoroalkene isosteres (43 and 45) through aldol reactions of Sm-dienolates with the carbonyl compounds. Of particular note, the use of the SmI2-HCHO reagent system with chiral enoate 34 provided D-Phe-psi[(Z)-CF=CH]-D/L-Ser isosteres (45), which could be converted to enantiomerically pure isosteres (49-52) that bore a variety of side chain functionalities at the a-position. This was achieved by a sequence of manipulations consisting of beta-lactone formation followed by chromatographic separation and ring-opening with soft nucleophiles. Included in the present work is the first utilization of a Rh-catalyzed Reformatsky reaction of chiral imines for the stereoselective preparation of alpha,alpha-difluoro-beta-amino acid derivatives (28 and 33). The appropriate choice of reagents (carbonyl compounds for kinetic trapping or ring-opening nucleophiles and imines for Reformatsky reactions) allows the presented methodology to yield various fluoroalkene isosteres possessing a wide range of side chain functionalities.