(2S,5S)-1-oxo-2,5-diphenyl-1lambda5-phospholan-1-amine | 1285720-82-2

• 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: (2S,5S)-1-oxo-2,5-diphenyl-1lambda5-phospholan-1-amine
• 英文别名: (2S,5S)-1-oxo-2,5-diphenyl-1λ5-phospholan-1-amine
• CAS: 1285720-82-2
• 化学式: C₁₆H₁₈NOP
• 分子量: 271.299
• InChiKey: KCDWOTJFJILANX-HOTGVXAUSA-N

物化性质

• 熔点：
  190-192 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  449.7±55.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  43.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2S,5S)-1-oxo-2,5-diphenyl-1lambda5-phospholan-1-amine 在 四氯化钛 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 8.75h， 生成 (2S,5S)-1-(((S)-2-nitro-1-phenylethyl)amino)-2,5-diphenylphospholane 1-oxide
  参考文献：
  名称：

  N-Phosphinyl Imine Chemistry (I): Design and Synthesis of Novel N-Phosphinyl Imines and their Application to Asymmetric aza-Henry Reaction

  摘要：

  Novel chiral N‐phosphinamide and N‐phosphinyl imines have been designed, synthesized and applied to asymmetric aza‐Henry reaction to give excellent chemical yields (92%– quant.) and diastereoselectivity (91% to >99%de). The reaction showed a great substrate scope in which aromatic/aliphatic aldehyde‐ and ketone‐derived N‐phosphinyl imines can be employed as electrophiles. The chiral N‐phosphinamide can be stored at room temperature for more than 2 months without inert gas protection, and chiral N‐phosphinyl imines were also proven to be highly stable at room temperature for a long period under inert gas protection. The N‐phosphinyl group enabled the product purification to be performed simply by washing crude product with EtOAc and hexane. This reaction joined other eight GAP (Group‐Assistant‐Purification) chemistry processes that were developed in our laboratories. The absolute configuration has been unambiguously determined by converting a β‐nitroamine product into a known N‐Boc sample.

  DOI：

  10.1111/j.1747-0285.2010.01047.x
• 作为产物：
  描述：

  (2S,5S)-(-)-1-chloro-1-oxo-2,5-diphenylphospholane 在 氨 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以98%的产率得到(2S,5S)-1-oxo-2,5-diphenyl-1lambda5-phospholan-1-amine
  参考文献：
  名称：

  N-Phosphinyl Imine Chemistry (I): Design and Synthesis of Novel N-Phosphinyl Imines and their Application to Asymmetric aza-Henry Reaction

  摘要：

  Novel chiral N‐phosphinamide and N‐phosphinyl imines have been designed, synthesized and applied to asymmetric aza‐Henry reaction to give excellent chemical yields (92%– quant.) and diastereoselectivity (91% to >99%de). The reaction showed a great substrate scope in which aromatic/aliphatic aldehyde‐ and ketone‐derived N‐phosphinyl imines can be employed as electrophiles. The chiral N‐phosphinamide can be stored at room temperature for more than 2 months without inert gas protection, and chiral N‐phosphinyl imines were also proven to be highly stable at room temperature for a long period under inert gas protection. The N‐phosphinyl group enabled the product purification to be performed simply by washing crude product with EtOAc and hexane. This reaction joined other eight GAP (Group‐Assistant‐Purification) chemistry processes that were developed in our laboratories. The absolute configuration has been unambiguously determined by converting a β‐nitroamine product into a known N‐Boc sample.

  DOI：

  10.1111/j.1747-0285.2010.01047.x

文献信息

• Chiral Phosphinyl Enamines and Their Asymmetric Reduction through Group-Assisted Purification Chemistry Leading to Enantiopure β-Amino Esters/Amides
  作者：Bo Jiang、Guigen Li、Shuo Qiao、Jianbin Wu、Junming Mo、Preston Spigener、Brian Zhao

  DOI：10.1055/s-0036-1589080

  日期：2017.11

  of new chiral N -phosphinyl β-enamino esters and amides were successfully prepared with excellent Z -stereoselectivity ( Z / E > 99:1 in nearly all cases). Group-assisted purification chemistry proved to be an efficient method for the asymmetric reduction of the resulting β-enamino esters/amides to give enantiopure β-amino esters/amides. The asymmetric reduction can be controlled efficiently by using

  以优异的Z-立体选择性（几乎所有情况下Z/E>99:1）成功制备了一系列新型手性N-膦酰基β-烯氨基酯和酰胺。组辅助纯化化学被证明是不对称还原所得 β-烯氨基酯/酰胺以得到对映体纯 β-氨基酯/酰胺的有效方法。通过使用氰基硼氢化钠和乙酸的组合可以有效地控制不对称还原。
• Synthesis of chiral <i>N</i>-phosphinyl α-imino esters and their application in asymmetric synthesis of α-amino esters by reduction
  作者：Yiwen Xiong、Haibo Mei、Lingmin Wu、Jianlin Han、Yi Pan、Guigen Li

  DOI：10.3762/bjoc.10.57

  日期：——

  A variety of chiral N-phosphinyl α-imino esters have been synthesized for the first time from ketoesters and phosphinylamide, which were then reduced by L-selectride to give the corresponding N-phosphinyl-protected α-amino esters. The reduction proceeded very well with excellent chemical yields (88–98%) as well as high diastereoselectivities (96:4 to 99:1). Some of these products could be obtained without column chromatography and recrystallization. The chiral phosphinyl auxiliary could be easily cleaved under acidic conditions.

  首次合成了一系列手性的N-磷酰基α-亚胺酯，这些酯是通过酮酯和磷酰胺合成的，然后通过L-selectride还原得到相应的N-磷酰基保护的α-氨基酯。还原反应的化学产率很高（88-98%），对映选择性也很高（96:4到99:1）。其中一些产物可以在不经过柱层析和再结晶的情况下获得。手性磷酰辅助基可以在酸性条件下轻松解除。
• Group-assisted purification (GAP) chemistry for the synthesis of Velcade via asymmetric borylation of <i>N</i>-phosphinylimines
  作者：Jian-bo Xie、Jian Luo、Timothy R Winn、David B Cordes、Guigen Li

  DOI：10.3762/bjoc.10.69

  日期：——

  A new approach to the anticancer drug Velcade was developed by performing asymmetric borylation of an imine anchored with a chiral N-phosphinyl auxiliary. Throughout the 7-step synthesis, especially in the imine’s synthesis and in the asymmetric borylation reactions, operations and work-up were conducted in simple and easy ways without any column chromatographic purification, which defines the GAP (group-assisted purification) chemistry concept. It was found that the optically pure isomer (dr > 99:1) can be readily obtained by washing the crude mixture of the asymmetric borylation reaction with hexane; the chiral N-phosphinyl auxiliary can be easily recovered after deprotection is finished. Several other N-phosphinylimines were also investigated for the asymmetric borylation reaction. The absolute configuration of the borylation product was confirmed by single crystal X-ray diffraction analysis.

  通过使用带手性N-膦辅助基的缩醛进行不对称硼化反应，开发了一种新的抗癌药物Velcade的方法。在整个7步合成中，特别是在缩醛的合成和不对称硼化反应中，操作和工作都是简单易行的，没有进行任何柱层析纯化，这定义了GAP（群辅助纯化）化学概念。发现通过用正己烷洗涤不对称硼化反应的混合物可以轻松地得到光学纯异构体（dr>99:1）；在去保护作用完成后，手性N-膦辅助基可以轻松地回收。还研究了几种其他的N-膦缩醛用于不对称硼化反应。通过单晶X射线衍射分析确定了硼化产物的绝对构型。