trans-5-hydroxymethyl-4-methyl-3-phenyl-4,5-dihydroisoxazole

• 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: trans-5-hydroxymethyl-4-methyl-3-phenyl-4,5-dihydroisoxazole
• 英文别名: [(4S,5S)-4-methyl-3-phenyl-4,5-dihydro-1,2-oxazol-5-yl]methanol
• 化学式: C₁₁H₁₃NO₂
• 分子量: 191.23
• InChiKey: HOYNJZVIJHYDIB-PSASIEDQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  41.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  环己氯化镁 、 trans-5-hydroxymethyl-4-methyl-3-phenyl-4,5-dihydroisoxazole 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 生成 (4,5-)-anti-(5,5')-anti-5--4-methyl-3-phenyl-4,5-dihydroisoxazole 、 (4,5-)-anti-(5,5')-syn-5--4-methyl-3-phenyl-4,5-dihydroisoxazole
  参考文献：
  名称：

  Nucleophilic additions to and reductiosn of 5-formyl-and 5-acyl-2-isoxazolines (4,5-dihydeoisoxazoles): a stereoselective route to β,γ-dihydroxy ketones

  摘要：

  Reductions of readily available 5-acyl-2-isoxazolines with L-Selectride follow the Felkin-Anh model and produce syn-5-hydroxyalkyl-2-isoxazolines with excellent (> 95:5) selectivities. Swern oxidation of 5-hydroxymethyl-2-isoxazolines, followed by direct addition of a Grignard reagent to the intermediate 5-formyl-2-isoxazolines, also follows the Felkin-Anh model and produces anti-5-hydroxyalkyl-2-isoxazolines with modest (80:20) to excellent (> 95:5) selectivity. In contrast, additions of Grignard reagents to 5-acyl-2-isoxazolines follow the chelation model, and give syn or anti products (depending on choice of acyl substituent and Grignard reagent) with good (90:10) to excellent selectivity. These selectivities are almost always far superior to those that can be obtained by direct nitrile oxide cycloaddition to a chiral allylic alcohol or ether. The resulting products are readily reduced to syn- or anti-beta,gamma-dihydroxy ketones. A speculative model to explain this surprising reversal in selectivity between formyl and acyl isoxazolines is proposed.

  DOI：

  10.1039/p19910002613
• 作为产物：
  描述：

  苯甲腈 N-氧化物 在 sodium tetrahydroborate 、 4 A molecular sieve 、 chiral amino indanol derivative 、 magnesium iodide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 生成 trans-5-hydroxymethyl-4-methyl-3-phenyl-4,5-dihydroisoxazole
  参考文献：
  名称：

  腈氧化物环加成反应中的手性路易斯酸催化

  摘要：

  我们描述了使用亚化学计量量的手性路易斯酸对不饱和烯烃进行高度区域选择性和对映选择性氧化腈环加成的例子。吡唑烷酮被证明是环加成中有效的非手性模板，提供的 C-加合物通常具有 >30:1 的选择性和 80-99% ee。为了避免涉及路易斯酸与胺碱配位的潜在问题，我们设计了一种新方法，使用 Amberlyst 21 作为碱从羟亚胺酰氯生成不稳定的腈氧化物。

  DOI：

  10.1021/ja0318636

文献信息

• Microwave Accelerated Cycloaddition Reactions of Nitrile Oxides and Allylic Alcohols
  作者：Ta-Jung Lu、Gwo-Ming Tzeng

  DOI：10.1002/jccs.200000022

  日期：2000.2

  promoting the cycloaddition reactions of allyl alcohols with nitrile oxides using a domestic microwave oven and a focused monomode microwave reactor have demonstrated that not only was the reaction time substantially reduced, but also the reaction yields were significantly improved over the conventional stirred reactions. Microwave irradiation alters the regioselectivity of the cycloaddition reaction which

  使用家用微波炉和聚焦单模微波反应器应用微波促进烯丙醇与氧化腈的环加成反应表明，与传统的搅拌反应器相比，不仅反应时间显着缩短，而且反应收率显着提高反应。微波照射改变了环加成反应的区域选择性，这有利于非氢键导向的环加合物异恶唑啉 4。
• Cycloadditions of Nitrile Oxides to α,β-Unsaturated Aldehydes. Frontier Orbital Interactions and Secondary Orbital Interactions at Work in Determining Regiochemistry
  作者：Lucio Toma、Paolo Quadrelli、Giancarlo Perrini、Remo Gandolfi、Cristiana Di Valentin、Antonino Corsaro、Pierluigi Caramella

  DOI：10.1016/s0040-4020(00)00356-2

  日期：2000.6

  oxides to crotonaldehyde and cinnamaldehyde has been determined and is dictated by frontier orbital interactions and secondary orbital interactions as well. In cycloadditions to α,β-unsaturated compounds the directive effect of the frontier orbital interactions can be diverted by steric drifts and secondary orbital interactions.

  已经确定了腈氧化物与巴豆醛和肉桂醛的环加成物的区域化学，并且也由边界轨道相互作用和次级轨道相互作用决定。在α，β-不饱和化合物的环加成反应中，前沿轨道相互作用的定向效应可通过空间漂移和次级轨道相互作用来转移。
• Asymmetric 1,3-Dipolar Cycloaddition Reactions of Nitrile Oxides Catalyzed by Chiral Binaphthyldiimine-Ni(II) Complexes
  作者：Hiroyuki Suga、Yuki Adachi、Kouhei Fujimoto、Yasuhisa Furihata、Teruko Tsuchida、Akikazu Kakehi、Toshihide Baba

  DOI：10.1021/jo802392c

  日期：2009.2.6

  enantioselectivities and regioselectivities were obtained for the reactions using pyrazolidinone derivatives as the dipolarophiles. For the cycloadditions of 2-(2-alkenoyl)-1-benzyl-5,5-dimethyl-3-pyrazolidinones catalyzed by (R)-BINIM-4(3,5-xylyl)-2QN-Ni(II) complex (30 mol %), the enantioselectivity varied from 75% to 95% ee. The reactions between several nitrile oxides and 2-acryloyl-1-benzyl-5,5-di

  在手性联萘二胺（BINIM）-Ni（II）配合物的存在下，几种腈氧化物与3-（2-烯基）-2-恶唑烷酮和2-（2-烯基）-3-吡唑烷酮衍生物之间进行不对称环加成反应。作为催化剂。使用（R）-BINIM-4（3,5-二甲苯基）-2QN-Ni（II）配合物（30 mol％），区域选择性好（4-Me / 5-Me = 85:15），对映选择性高（96％ee）对于可分离的2,4,6-三甲基苄腈氧化物与3-巴豆酰基-5,5-二甲基-2-恶唑烷酮之间的反应，获得4-Me加合物的4-Me。在MS4Å存在下，由相应的羟基苯甲酰氯生成的取代的和未取代的苯甲腈氧化物和脂族腈氧化物与3-巴豆酰基-5,5-二甲基-2-恶唑烷酮，5,5-二甲基-3- （2-戊烯基）-2-恶唑烷酮，5,5-二甲基-3- [3-（乙氧基羰基）丙烯酰基] -2-恶唑烷酮，1-苄基-2-巴豆酰基-5,5-二甲基-3-吡唑烷酮和（R）-BI
• Regiocontrol of nitrile oxide cycloadditions to allyl alcohols. Synthesis of 4-substituted and 4,4-disubstituted 5-hydroxymethyl-2-isoxazolines
  作者：Shuji Kanemasa、Masaki Nishiuchi、Eiji Wada

  DOI：10.1016/s0040-4039(00)91622-8

  日期：1992.3

  The first regiocontrol of nitrile oxide cycloadditions is described. Reaction of benzonitrile oxide with (E)-2-butenol is highly accelerated by the presence of a magnesium alkoxide, and this reaction proceeds in an exclusively regioselective manner to produce 5-hydroxymethyl-4-methyl-3-phenyl-2-isoxazoline as the sole cycloadduct. Synthetic applications to other substituted allyl alcohols are discussed.
• First Successful Metal Coordination Control in 1,3-Dipolar Cycloadditions. High-Rate Acceleration and Regio- and Stereocontrol of Nitrile Oxide Cycloadditions to the Magnesium Alkoxides of Allylic and Homoallylic Alcohols
  作者：Shuji Kanemasa、Masaki Nishiuchi、Akio Kamimura、Kenzi Hori

  DOI：10.1021/ja00085a012

  日期：1994.3

  The first successful control of stereo- and regioselectivity in 1,3-dipolar cycloadditions by metal coordination is described. The presence of magnesium ions dramatically accelerates nitrile oxide dipolar cycloadditions to allylic alcohols, improving both the regio- and stereoselectivity of the reaction. For example, cycloadditions to terminal allylic alcohols bearing alpha-chirality produce syn-stereoisomers of 2-isoxazolines selectively, and reactions involving the magnesium alkoxides of internal allylic alcohols are exclusively regioselective in favor of 5-hydroxymethyl-2-isoxazolines. Metal alkoxides other than magnesium, such as lithium, zinc, and aluminum alkoxides, are less effective. These reactions involve the formation of activated intermediates in which a nitrile oxide and an allylic alkoxide coordinate to the magnesium ion. Theoretical calculations indicate that the formation of the coordinated intermediates enhances the rate of cycloaddition and also improves the syn-selectivity.