| 172016-08-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• CAS: 172016-08-9
• 化学式: C₁₆H₂₃NO₂
• 分子量: 261.364
• InChiKey: CHWBUFHQDBPFRL-XPKDYRNWSA-N

物化性质

• 沸点：
  409.5±24.0 °C(Predicted)
• 密度：
  1.102±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.19
• 重原子数：
  19.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  40.54
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  在 重铬酸吡啶 、 sodium azide 、 四溴化碳 、 4 A molecular sieve 、 二异丁基氢化铝 、 三苯基膦 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 (1R,2S)-2-((S)-1-Azido-ethyl)-1-phenyl-cyclopropanecarboxylic acid diethylamide
  参考文献：
  名称：

  Conformational Restriction by Repulsion between Adjacent Substituents on a Cyclopropane Ring:  Design and Enantioselective Synthesis of 1-Phenyl-2-(1-aminoalkyl)-N,N-diethylcyclopropanecarboxamides as Potent NMDA Receptor Antagonists

  摘要：

  Adjacent substituents on a cyclopropane ring mutually exert steric repulsion quite significantly, because they are fixed in eclipsed conformation to each other. Based on this structural feature of the cyclopropane ring, conformationally restricted analogs of milnacipran (1), namely 1-phenyl-2-(1-aminoalkyl)-N,N-diethylcyclopropanecarboxamides (2, 3, ent-2, and ent-3) were designed as potent NMDA receptor antagonists and were synthesized highly enantioselectively. Reaction of (R)epichlorohydrin [(R)-5] and phenylacetonitrile (6) in the presence of NaNH2 in benzene gave a chiral cyclopropane derivative that was isolated as lactone 4 with 96% ee in 67% yield, after alkaline hydrolysis of the cyano group. The nucleophilic addition reaction of Grignard reagents to aldehyde 10, which was readily prepared from 4, proceeded highly selectively from the si-face to afford addition products 11 in high yields. Although hydride reduction of the corresponding ketone 15b, prepared from 11b, with L-Selectride also proceeded highly diastereo selectively, the facial selectivity was reversed to give the re-face addition product 11b. On the other hand, reduction of 15 with DIBAL-H afforded the si-face addition product 12 in high yields. These results suggested that these nucleophilic addition reactions proceeded via either the bisected s-trans or s-cis conformation of the cyclopropylcarbonyl derivatives. From 11 and 12, the target conformationally resticted analogs, 2 and 3, were synthesized, respectively. Starting from (S)-epichlorohydrin [(S)-5], their corresponding enantiomers, ent-a and ent-3, were also synthesized. The structures of the conformationally restricted analogs detected by the X-ray crystallographic analysis suggested that their conformations can be restricted as we hypothesized. Thus, a new method for restricting the conformation of cyclopropane derivatives has been developed.

  DOI：

  10.1021/jo9518056
• 作为产物：
  描述：

  1alpha-Phenyl-2beta-(hydroxymethyl)cyclopropanecarbonitrile 在 盐酸 、 氢氧化钾 、 lithium amide 、 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  （+）-和（-）-米那普仑及其构象受限的类似物的合成

  摘要：

  （R）-表氯醇[（R）-5 ]与苯乙腈（6）在NaNH 2的存在下在苯中的反应生成环丙烷衍生物，其被分离为内酯4 [（1 S，2 R）-2-氧-在氰基进行碱性水解后，96％ee的1-苯基-3-氧杂双环[3,1,0]己烷]的收率为67％。化合物4容易地转化为（+）-米那普仑[（+）- 1 ]，由此证实了（+）- 1的绝对立体化学。（1 S，2 R）-1-苯基-2-[（（S）-1-氨乙基]-环丙烷-N，N-diethylcarboxamindes（2），构象受限的1的类似物，还从4合成高对映体纯度。从（S）-表氯醇[（S）-5 ]开始，还合成了它们相应的对映异构体，即（-）-米那普仑[（-）- 1 ]和ent-2 。

  DOI：

  10.1016/0040-4039(95)02221-x

文献信息

• Highly stereoselective nucleophilic addition to cyclopropyl carbonyls: The facial selectivity in the cyclopropyl ketones is opposite to that in the corresponding aldehyde
  作者：Shizuka Ono、Satoshi Shuto、Akira Matsuda

  DOI：10.1016/0040-4039(95)02133-7

  日期：1996.1

  Nucleophilic addition reaction of Grignard reagents to cyclopropylcarbaldehyde 4 proceeded highly selectively from the si-face to afford 5 in high yield. Although hydride reduction of the corresponding ketone 7 with L-Selectride® also proceeded highly diastereoselectively, the facial selectivity was reversed to give the re-face addition product 5. On the other hand, reduction of 7 with DIBAL-H afforded

  格氏试剂的亲核加成反应来cyclopropylcarbaldehyde 4从进行高度选择性SI面取向，得到5以高收率。虽然相应的酮的氢化物还原7与三仲丁基硼氢化锂®也进行高度非对映选择性，面部选择性被逆转，得到重-面加成产物5。另一方面，用DIBAL-H还原7得到高产率的硅表面加成产物6。结果表明，这些亲核加成反应是通过两等分的s-进行的。反式或小号-顺式环丙烷衍生物的构象。
• The unusual 1,4-chelation-controlled nucleophilic addition to aldehydes with high stereoselectivity. A systematic study of stereoselectivity in the addition reaction of carbon nucleophiles to cis-substituted cyclopropanecarbaldehydes
  作者：Yuji Kazuta、Hiroshi Abe、Tamotsu Yamamoto、Akira Matsuda、Satoshi Shuto

  DOI：10.1016/j.tet.2004.05.063

  日期：2004.7

  The addition reaction of carbon nucleophiles to cis-substituted cyclopropanecarbaldehydes was systematically investigated. Ab initio calculations of model cyclopropanecarbaldehydes suggested that the bisected s-cis and s-trans conformers are the only two minimum energy conformers, which are stabilized due to the pi-donating stereoelectronic effect of the cyclopropane ring. The experimental results of a series of substrates, that is, cyclopropanecarbaldehydes 1-5 bearing a cis-(tert-butyldiphenyisilyloxy)methyl group, a cis-benzyloxymethyl group, a cis-(p-methoxybenzyloxy)methyl group, cis-N,N-diethylcarbamoyl and trans-phenyl groups, and cis-(tert-butyldiphenylsilyloxy)methyl and trans-phenyl groups, respectively, showed that highly anti-selective Grignard additions could be realized. It turned out that it occurred via an unusual 7-membered 1,4-chelation-controlled pathway. Highly stereoselective Grignard addition via the chelation-controlled pathway occurred even in the reaction of the usually non-chelating silyl ether-type substrate 5. The results have great importance because the 1,4-chelation-controlled stereoselective addition reactions can indeed be realized. Under non-chelation conditions, the syn-products were produced with moderate stereoselectivity, which are likely to be formed via the bisected s-cis conformation-like transition state stabilized by the characteristic orbital interaction. These reactions, especially the chelation-controlled reaction, should be useful because of their t stereoselectivity and stereochemical predictability. (C) 2004 Elsevier Ltd. All rights reserved.