(3aR,7aR)-2-((4-(benzyloxy)benzylidene)amino)-1,3-diisopropyloctahydrobenzo[d][1,3,2]diazaphosphole 2-oxide | 1186139-53-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (3aR,7aR)-2-((4-(benzyloxy)benzylidene)amino)-1,3-diisopropyloctahydrobenzo[d][1,3,2]diazaphosphole 2-oxide
• CAS: 1186139-53-6
• 化学式: C₂₆H₃₆N₃O₂P
• 分子量: 453.565
• InChiKey: ZHRSFKVGNTUKCH-CLJLJLNGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.54
• 重原子数：
  32.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  45.14
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  2-溴丙酸甲酯 、 (3aR,7aR)-2-((4-(benzyloxy)benzylidene)amino)-1,3-diisopropyloctahydrobenzo[d][1,3,2]diazaphosphole 2-oxide 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 9.2h， 以70%的产率得到methyl (2S,3S)-1-[(3aR,7aR)-2-oxo-1,3-di(propan-2-yl)-3a,4,5,6,7,7a-hexahydrobenzo[d][1,3,2]diazaphosphol-2-yl]-3-(4-phenylmethoxyphenyl)aziridine-2-carboxylate
  参考文献：
  名称：

  N,N-二异丙基-N-膦酰基亚胺导致氮丙啶-2-羧酸酯的有效不对称合成†

  摘要：

  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。

  DOI：

  10.1039/c3ob40251g

文献信息

• 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 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.
• Chiral N-phosphonyl imine chemistry: Asymmetric synthesis of α,β-diamino esters by reacting phosphonyl imines with glycine enolates
  作者：Teng Ai、Guigen Li

  DOI：10.1016/j.bmcl.2009.03.001

  日期：2009.7

  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.
• Asymmetric Synthesis of α-Amino-1,3-dithianes via Chiral <i>N</i>-Phosphonyl Imine-Based Umpolung Reaction Without Using Chromatography and Recrystallization
  作者：Padmanabha V. Kattamuri、Teng Ai、Suresh Pindi、Yinwei Sun、Peng Gu、Min Shi、Guigen Li

  DOI：10.1021/jo200070d

  日期：2011.4.15

  A series of alpha-amino-1,3-dithianes have been synthesized via the asymmetric Umpolung reaction of 2-lithio-1,3-dithianes with chiral N-phosphonyl imines in good chemical yields (up to 82%) and good to excellent diastereoselectivities (>99:1). The manner by which chiral N-phosphonyl imines are slowly added into the solution of 2-lithio-1,3-dithiane was found to be crucial for achieving excellent diastereoselectivity. The current synthesis was proven to follow the GAP chemistry (group-assistant-purification chemistry) process, which avoids traditional purification techniques of chromatography or recrystallization, i.e., the pure chiral alpha-amino-1,3-dithianes attached with the chiral N-phosphonyl group were readily obtained by washing the solid crude products with hexane or a mixture of hexane ethyl acetate.