N-[(3aR,7aR)-2-oxido-1,3-di(propan-2-yl)-3a,4,5,6,7,7a-hexahydrobenzo[d][1,3,2]diazaphosphol-2-ium-2-yl]-1-(4-chlorophenyl)methanimine | 1186139-57-0

• 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: N-[(3aR,7aR)-2-oxido-1,3-di(propan-2-yl)-3a,4,5,6,7,7a-hexahydrobenzo[d][1,3,2]diazaphosphol-2-ium-2-yl]-1-(4-chlorophenyl)methanimine
• CAS: 1186139-57-0
• 化学式: C₁₉H₂₉ClN₃OP
• 分子量: 381.886
• InChiKey: VTVNYVBXOJDPRC-RTBURBONSA-N

物化性质

• 沸点：
  471.5±47.0 °C(predicted)
• 密度：
  1.26±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  41.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  二苯亚甲基甘氨酸乙酯 、 N-[(3aR,7aR)-2-oxido-1,3-di(propan-2-yl)-3a,4,5,6,7,7a-hexahydrobenzo[d][1,3,2]diazaphosphol-2-ium-2-yl]-1-(4-chlorophenyl)methanimine 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 0.67h， 生成 ethyl (2S,3S)-3-(4-chlorophenyl)-3-(((3aR,7aR)-1,3-diisopropyl-2-oxidooctahydrobenzo[d][1,3,2]diazaphosphol-2-yl)amino)-2-((diphenylmethylene)amino)propanoate
  参考文献：
  名称：

  Chiral N-phosphonyl imine chemistry: Asymmetric synthesis of α,β-diamino esters by reacting phosphonyl imines with glycine enolates

  摘要：

  Chiral phosphonyl imines attached with N-isopropyl protection group were found to react with lithium glycine enolates under convenient conditions to give alpha,beta-diamino esters. Thirteen examples have been examined in good to excellent chemical yields (85-97%) diastereoselectivity (up to 99% de). By treating with HBr at room temperature, the chiral auxiliary can be readily removed and recycled. The absolute structure has been unambiguously determined by converting a product to a known sample. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2009.03.001
• 作为产物：
  描述：

  (3aR,7aR)-2-hydroxy-2-imino-1,3-di(propan-2-yl)-3a,4,5,6,7,7a-hexahydrobenzo[d][1,3,2]diazaphosphole 、 4-氯苯甲醛 在 四氯化钛 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.5h， 生成 N-[(3aR,7aR)-2-oxido-1,3-di(propan-2-yl)-3a,4,5,6,7,7a-hexahydrobenzo[d][1,3,2]diazaphosphol-2-ium-2-yl]-1-(4-chlorophenyl)methanimine
  参考文献：
  名称：

  手性N-膦酰基亚胺与氮杂内酯的不对称曼尼希型反应的基团辅助纯化化学反应，导致合成α-季α，β-二氨基酸衍生物†

  摘要：

  在室温下方便的条件下，建立了手性N-膦酰基亚胺和a内酯[恶唑-5（4 H）-ones]之间的不对称曼尼希型反应。在不使用任何碱，添加剂或催化剂的情况下进行反应，以实现高达32个实例的优异的化学收率和非对映选择性。α-季顺-α，β二氨基酸产物简单地通过洗涤纯化，用助溶剂，粗混合物，继组辅助纯化化学/技术，而不涉及传统的色谱法或重结晶法。辅助部件可以很容易地取出并回收再利用。通过X射线结构分析明确分配了绝对构型。

  DOI：

  10.1021/acs.joc.7b02556

文献信息

• N,N-Diisopropyl-N-phosphonyl imines lead to efficient asymmetric synthesis of aziridine-2-carboxylic esters
  作者：Padmanabha V. Kattamuri、Yiwen Xiong、Yi Pan、Guigen Li

  DOI：10.1039/c3ob40251g

  日期：——

  Highly diastereoselective asymmetric synthesis of chiral aziridine-2-carboxylic esters is reported for 20 examples with good yields (51–87%) and excellent diastereoselectivities (>99 : 1 dr for most cases). The modified N-phosphonyl imines have proven to be superior to previous imine auxiliaries for the aza Darzens reaction by using a secondary isopropyl group to replace the primary benzyl group for

  据报道，手性氮丙啶-2-羧酸酯的高度非对映选择性不对称合成有 20 个实例，具有良好的产率（51-87%）和出色的非对映选择性（大多数情况下 >99:1 dr）。通过使用仲异丙基取代N , N的伯苄基，已证明改性N - 膦酰基亚胺在 aza Darzens 反应中优于以前的亚胺助剂。-二氨基保护。同时，发现在 4 Å 分子筛存在的情况下，在该温度下将预冷的亚胺溶液在 -78 °C 下缓慢加入到预先形成的 β-溴化烯醇锂混合物中的特殊操作对产率至关重要和非对映选择性。本方法可以提供对 β-羟基α-氨基酸和其他重要氨基构建块的简单和通用的访问。
• Group-assisted Purification (GAP) Chemistry/Technology in Synthesizing the Chiral Intermediate of Rivastigmine and Its <i>α</i>-Alkyl Benzylamine Analogues
  作者：Bing Yang、Chun-Yan Zhang、Jing Xu、Da-Jun Zheng、Xiao-Ying Wang、Hong Dai、Yu-Jun Shi、Hai-Liang Zhu

  DOI：10.1246/cl.190288

  日期：2019.9.5

  Introduction of (S)-configuration is the key step in the synthesis of the anti-dementia drug Rivastigmine. Twenty-one alkylation products were obtained through simple washing with hexane/ethyl acet...

  (S)-构型的引入是合成抗痴呆药物卡巴拉汀的关键步骤。用正己烷/乙酸乙酯简单洗涤得到21种烷基化产物...
• Asymmetric aza-Morita–Baylis–Hillman reactions of chiral N-phosphonyl imines with acrylates via GAP chemistry/technology
  作者：Bing Yang、Xiaozhou Ji、Yunsheng Xue、Haowei Zhang、Minxing Shen、Bo Jiang、Guigen Li

  DOI：10.1039/c6ob00847j

  日期：——

  Chiral N-phosphonyl imines have been proven to be efficient electrophilic acceptors for asymmetric aza-Morita–Baylis–Hillman (aza-MBH) reactions with acrylates under convenient conditions. Thirty examples of β-amino acrylates were generated in high yields (up to 99.4%) and diastereoselectivity (up to >99 : 1 dr) in an atom-economical fashion. The synthesis was proved to follow the GAP (group-assisted

  已证明手性N-膦酰基亚胺是在方便条件下与丙烯酸酯进行不对称氮杂-Morita-Baylis-Hillman（aza-MBH）反应的有效亲电子受体。以原子经济的方式，以高收率（高达99.4％）和非对映选择性（高达> 99：1 dr）生成了30个β-氨基丙烯酸酯实例。已证明该合成遵循GAP（基团辅助纯化）化学方法，即，无需使用色谱法或色谱法，只需用己烷/乙酸乙酯（v / v，10/1）洗涤粗产物即可简单地获得纯产物。重结晶。还进行了DFT计算，以支持考虑非对映选择性高的不对称诱导模型。
• The GAP chemistry for chiral N-phosphonyl imine-based Strecker reaction
  作者：Parminder Kaur、Walter Wever、Suresh Pindi、Raizada Milles、Peng Gu、Min Shi、Guigen Li

  DOI：10.1039/c1gc15029d

  日期：——

  Chiral N-phosphonyl imines were found to be efficient electrophiles for reaction with diethylaluminium cyanide, a non-volatile and inexpensive cyanide source. The reaction produced chiral Strecker adducts, α-aminonitriles, in excellent chemical yields (94–98%) and diastereoselectivities (95 : 5 to >99%). This synthesis was confirmed to follow the GAP chemistry (group-assistant-purification chemistry) process, which can avoid traditional chromatography and recrystallization purifications, i.e., the pure chiral α-aminonitriles bearing a chiral N-phosphonyl group can be simply obtained by washing the solid crude products with hexane. The chiral N-phosphonyl auxiliary can be easily cleaved under mildly acidic conditions and quantitatively recycled by a one-time extraction with n-butanol.

  研究发现，手性 N-膦酰亚胺是与氰化二乙基铝（一种非挥发性的廉价氰化物来源）反应的高效亲电体。反应生成了手性 Strecker 加合物--α-氨基硝酰胺，化学收率（94-98%）和非对映选择性（95:5->99%）都非常好。经证实，该合成采用了 GAP 化学（基团辅助纯化化学）工艺，可避免传统的色谱法和重结晶纯化，即只需用正己烷洗涤固体粗产物，即可获得带有手性 N-膦酰基的纯手性 α-氨基硝酸酯。手性 N-膦酰基助剂可在弱酸性条件下轻松裂解，并通过正丁醇一次性萃取定量回收。
• Asymmetric Carbamoyl Anion Additions to Chiral <i>N</i>-Phosphonyl Imines via the GAP Chemistry Process and Stereoselectivity Enrichments
  作者：Cole W. Seifert、Suresh Pindi、Guigen Li

  DOI：10.1021/jo5024443

  日期：2015.1.2

  Carbamoyl anions were found to smoothly react with chiral N-phosphonyl imines in toluene at -78 degrees C to r.t. using LiHMDS as the base. Group-assisted purification (GAP) has been utilized to give the pure amides without using column chromatography or recrystallization. The asymmetric reaction resulted in chiral N-phosphonyl amino amides with good to excellent yields (71-99%) and good crude diastereoselectivities (dr 84:16-95:5). In this GAP procedure, the crude solids are washed with diethyl ether to afford the pure products, as revealed by H-1 NMR analysis; GAP washing consistently increases the diastereopurity of the products, resulting in excellent diastereoselectivities, often with final dr > 99:1. Interestingly, the diastereoenriched products can be obtained either in the ether solution or as the suspended solid, depending on the substrate.