4-methyl-2,2-pentamethylene-2,5-dihydrooxazole | 146377-35-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑啉类
• 英文名称: 4-methyl-2,2-pentamethylene-2,5-dihydrooxazole
• 英文别名: 4-methyl-2,2-pentamethylene-2,5-dihydrooxazol；3-Methyl-1-oxa-4-azaspiro[4.5]dec-3-ene
• CAS: 146377-35-7
• 化学式: C₉H₁₅NO
• 分子量: 153.224
• InChiKey: HUIITPPXOJQSCJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  21.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-methyl-2,2-pentamethylene-2,5-dihydrooxazole 在 正丁基锂 、 二异丙胺 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 2.0h， 生成 (-)-(Ss,7'S)-7'-methyl-8'-[(4-methylphenyl)sulfinyl]-6',7'-dihydrospiro[cyclohexane-1,3'-[1,3]oxazolo[3,4-a]pyridin]-5'(1'H)-one
  参考文献：
  名称：

  Diastereoselective synthesis of 4-substituted 5-(p-tolylsulfinyl)-5,6-dehydropiperidin-2-ones. A new approach to methyl l-(2S,4S)-4-methyl-6-oxopipecolate

  摘要：

  The sulfoxide-mediated diastereoselective Michael reaction of homochiral alpha-sulfinylketimines 1a-d and beta-substituted ene esters 2a-d (Hua's reaction) was explored. Straight forward cyclization of the open-chain adducts take place under the reaction conditions to provide the 4-substituted 5-(p-tolylsulfinyl)-5,6-dehydropiperidin-2-ones 3 and 7-12, whose stereochemistry is formed in the prior step. Furthermore. the role of the metal ion of the aza-enolate reagents and the steric demands of the O-alkyl ester group have been examined. It seems that the anti-diastereoselectivity depends on metal chelation by the oxygen of the ester as well as the oxygen of the sulfinyl group and the nitrogen in the aza-enolate ((Z)-configuration). In addition, the synthesis of methyl L-(2S,4S)-4-methyl-6-oxopipecolate has been achieved from the suitably functionalized 2-sulfinylketimine 1a (five steps; overall yield: 53-65%). (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(01)00553-5
• 作为产物：
  描述：

  7-甲基-1-氮杂-4-氧杂螺[4.5]癸烷 在 18-冠醚-6 、 次氯酸叔丁酯 、 碳酸氢钠 作用下， 以 乙醚 为溶剂， 反应 15.0h， 生成 4-methyl-2,2-pentamethylene-2,5-dihydrooxazole
  参考文献：
  名称：

  2，2-二取代的2，5-二氢-4-甲基恶唑的合成。

  摘要：

  由2-氨基丙醇分三步合成2，2-二取代的2，5-二氢-4-甲基恶唑（1）。可以将3-Oxazolines 1转化为各种α-亚磺酰基酮亚胺，例如（S S）-{（4-甲基苯基）亚磺酰基甲基} -2,2-二乙基-2,5-二氢恶唑（5），并用Dibal- H得到3-羟基-2-氨基丙基亚砜7。

  DOI：

  10.1016/0040-4039(93)88036-i

文献信息

• Asymmetric synthesis of β-amino-γ-hydroxysulfoxides
  作者：Noureddine Khiar、Inmaculada Fernández、Felipe Alcudia、Duy H. Hua

  DOI：10.1016/s0040-4039(00)61657-x

  日期：1993.1

  Optically pure [4-(3′-oxazoline)]methyl methyl- and p-tolylsulfoxides (5R, 5S, 6R and 6S) were prepared from the enolate of the 3-oxazoline 4 and the corresponding o.p. diacetone-D-glucofuranosyl methanesulfinate and menthyl p-toluenesulfinate. The highly diastereoselective reduction of these substrates was successfully achieved using DIBAL/ZnCl2 at −78°C. In this way, four o.p. N-cyclohexyl-β-ami

  由3-恶唑啉4的烯醇化物和相应的对二丙酮-D-葡糖呋喃糖基甲亚磺酸盐和对甲苯磺酸制备光学纯的[4-（3'-恶唑啉）]甲基甲基和对-甲苯磺酸亚砜（5R，5S，6R和6S）。对甲苯磺酸薄荷酯。使用-78°C的DIBAL / ZnCl 2成功实现了这些底物的非对映选择性的高度还原。以此方式，获得了四种op N-环己基-β-氨基-γ-羟基亚砜，它们是各种生物活性分子的不对称合成中的手性关键中间体。
• Stereoselective cyanosilylation of α-sulfinylketimines or its covalently stabilized enamine tautomers. Synthesis of enantiomerically pure α-sulfinylmethyl-α-amino nitriles
  作者：Hassan Acherki、Carlos Alvarez-Ibarra、Alfonso-de-Dios、Maria L Quiroga

  DOI：10.1016/s0040-4020(02)00234-x

  日期：2002.4

  alpha-Sulfinylketimmes and beta-sulfinylenamines undergo reaction with delivery cyanide reagents such as TMSCN or TBDMSCN in the presence of either stoichiometric excesses of ZnCl2 or ZnBr2, or catalytic amount of Yb(TfO)(3). The use of ZnCl2 in alcohol solvents provides the best diastercoselectivity. It is mediated by a chelated transition state, the p-tolyl group driving the anti attack of the reagent. By using Yb(TfO)(3) poor diastereoselectivities but good yields are obtained. It seems that an iminium derivative originated by metal coordination with either the nitrogen or oxygen atom in the substrate is responsible for the observed results. Interestingly, beta-sulfinylenamines provide analogous a-amino nitriles in the same reaction conditions. It allowed the cyanosilylation of the covalently stabilized enamines arising from unstable beta-sulfinyl aldehydes. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Synthesis of 2,2-disubstituted 2,5-dihydro-4-methyloxazoles.
  作者：Duy H. Hua、Noureddine Khiar、Fengqi Zhang、Laurent Lambs

  DOI：10.1016/0040-4039(93)88036-i

  日期：1992.12

  2,2-Disubstituted 2,5-dihydro-4-methyloxazoles (1) were synthesized from 2-aminopropanol in three steps. 3-Oxazolines 1 can be converted into various α-sulfinyl ketimines such as (SS)-(4-methylphenyl)sulfinylmethyl}-2,2-diethyl-2,5-dihydrooxazole (5) which was stereoselectively reduced with Dibal-H to give 3-hydroxy-2-aminopropyl sulfoxide 7.

  由2-氨基丙醇分三步合成2，2-二取代的2，5-二氢-4-甲基恶唑（1）。可以将3-Oxazolines 1转化为各种α-亚磺酰基酮亚胺，例如（S S）-（4-甲基苯基）亚磺酰基甲基} -2,2-二乙基-2,5-二氢恶唑（5），并用Dibal- H得到3-羟基-2-氨基丙基亚砜7。
• Diastereoselective synthesis of 4-substituted 5-(p-tolylsulfinyl)-5,6-dehydropiperidin-2-ones. A new approach to methyl l-(2S,4S)-4-methyl-6-oxopipecolate
  作者：Hassan Acherki、Carlos Alvarez-Ibarra、Alfonso de Dios、Marta Gutiérrez、Marı́a L. Quiroga

  DOI：10.1016/s0957-4166(01)00553-5

  日期：2001.12

  The sulfoxide-mediated diastereoselective Michael reaction of homochiral alpha-sulfinylketimines 1a-d and beta-substituted ene esters 2a-d (Hua's reaction) was explored. Straight forward cyclization of the open-chain adducts take place under the reaction conditions to provide the 4-substituted 5-(p-tolylsulfinyl)-5,6-dehydropiperidin-2-ones 3 and 7-12, whose stereochemistry is formed in the prior step. Furthermore. the role of the metal ion of the aza-enolate reagents and the steric demands of the O-alkyl ester group have been examined. It seems that the anti-diastereoselectivity depends on metal chelation by the oxygen of the ester as well as the oxygen of the sulfinyl group and the nitrogen in the aza-enolate ((Z)-configuration). In addition, the synthesis of methyl L-(2S,4S)-4-methyl-6-oxopipecolate has been achieved from the suitably functionalized 2-sulfinylketimine 1a (five steps; overall yield: 53-65%). (C) 2002 Elsevier Science Ltd. All rights reserved.