(7'S,8a'S)-7'-methyltetrahydrospiro[cyclohexane-1,3'-[1,3]oxazolo[3,4-a]pyridin]-5'(1'H)-one | 244104-70-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (7'S,8a'S)-7'-methyltetrahydrospiro[cyclohexane-1,3'-[1,3]oxazolo[3,4-a]pyridin]-5'(1'H)-one
• 英文别名: (+)-(7S,8aS)-7-methyl-3,3-pentamethylene-1,2,3,5,6,7,8,8a-octahydro-2-oxa-5-indolizinone；(7S,8aS)-7-methylspiro[6,7,8,8a-tetrahydro-1H-[1,3]oxazolo[3,4-a]pyridine-3,1'-cyclohexane]-5-one
• CAS: 244104-70-9
• 化学式: C₁₃H₂₁NO₂
• 分子量: 223.315
• InChiKey: DOHHWSMUHNAAHG-QWRGUYRKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (7'S,8a'S)-7'-methyltetrahydrospiro[cyclohexane-1,3'-[1,3]oxazolo[3,4-a]pyridin]-5'(1'H)-one 在 jones reagent 、 溶剂黄146 作用下， 以 水 、 丙酮 为溶剂， 反应 18.0h， 生成 (2S,4S)-4-甲基-6-氧代-2-哌啶羧酸
  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：

  (-)-(Ss,7'R)-7'-methyl-8'-[(4-methylphenyl)sulfinyl]-6',7'-dihydrospiro[cyclohexane-1,3'-[1,3]oxazolo[3,4-a]pyridin]-5'(1'H)-one 在 Raney Nikel W-2 作用下， 以 乙醇 为溶剂， 反应 0.33h， 以91%的产率得到(7'S,8a'S)-7'-methyltetrahydrospiro[cyclohexane-1,3'-[1,3]oxazolo[3,4-a]pyridin]-5'(1'H)-one
  参考文献：
  名称：

  Straightforward synthesis of [(2S,4R)-1-cyclohexyl-4-methylpiperidin-2-yl]methanol and [(2S,4R)-1-cyclohexyl-4-methylpiperidin-2-yl](diphenyl)methanol: novel chiral ligands for the catalytic addition of diethylzinc to benzaldehyde to give rise to an extensive turn in the sense of asymmetric induction

  摘要：

  Enantiopure [(2S,4R)-1-cyclohexyl-4-methylpiperidin-2-yl]methanol 5a and [(25,4R)-1-cyclohexyl-4-methylpiperidin-2-yl]-(diphenyl)methanol 5b, new beta-amino alcohols based on L-pipecolinic acid (homoproline), have been prepared straightforwardly from rac-alaninol and rac-2-amino-1,1-diphenylpropan-1-ol, respectively. The described route constitutes as a model procedure for the preparation of other related C(4) or/and C(3)-substituted 2-piperidinylmethanols.The new chiral ligands have shown a singular behaviour on the stereocontrol of the benchmark reaction of benzaldehyde and diethylzinc compared with other C(4)-unsubstituted analogues prepared by ourselves from L-pipecolinic acid (compounds 5c, 5d, 5e and 5f). The catalytic activity, the sense of asymmetric induction and the degree of the enantioselectivity depend on the appropriate combination of the substituents on the structural scaffold, but also on the metal-alkoxide involved in the catalysis (zinc or lithium alkoxides). The enantioselective addition of diethylzinc to benzaldehyde mediated by ligands 5a and 5c has been studied with OFT methods. The theoretical evaluation was performed in connection with a working hypothesis based on the different loadings of cis- and trans-catalysts in the reaction medium. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2010.07.035

文献信息

• Sulfoxide-mediated diastereoselective Michael additions. New enantioselective synthesis of C-4 substituted 2-pyroaminoadipic acids
  作者：Hassan Acherki、Carlos Alvarez-Ibarra、Alicia Barrasa、Alfonso de Dios

  DOI：10.1016/s0040-4039(99)01047-3

  日期：1999.7

  Diastereoselective reactions of suitably functionalized homochiral beta-iminosulfoxides with Michael accepters provide a new and efficient route for the asymmetric synthesis of C-4 substituted 2-pyroaminoadipates. Extension of the scope of the sulfoxide-mediated aza-enolate conjugate addition (Hua's reaction) has also been explored. (C) 1999 Elsevier Science Ltd. All rights reserved.
• Straightforward synthesis of [(2S,4R)-1-cyclohexyl-4-methylpiperidin-2-yl]methanol and [(2S,4R)-1-cyclohexyl-4-methylpiperidin-2-yl](diphenyl)methanol: novel chiral ligands for the catalytic addition of diethylzinc to benzaldehyde to give rise to an extensive turn in the sense of asymmetric induction
  作者：Carlos Alvarez-Ibarra、Juan F. Collados Luján、María L. Quiroga-Feijóo

  DOI：10.1016/j.tetasy.2010.07.035

  日期：2010.10

  Enantiopure [(2S,4R)-1-cyclohexyl-4-methylpiperidin-2-yl]methanol 5a and [(25,4R)-1-cyclohexyl-4-methylpiperidin-2-yl]-(diphenyl)methanol 5b, new beta-amino alcohols based on L-pipecolinic acid (homoproline), have been prepared straightforwardly from rac-alaninol and rac-2-amino-1,1-diphenylpropan-1-ol, respectively. The described route constitutes as a model procedure for the preparation of other related C(4) or/and C(3)-substituted 2-piperidinylmethanols.The new chiral ligands have shown a singular behaviour on the stereocontrol of the benchmark reaction of benzaldehyde and diethylzinc compared with other C(4)-unsubstituted analogues prepared by ourselves from L-pipecolinic acid (compounds 5c, 5d, 5e and 5f). The catalytic activity, the sense of asymmetric induction and the degree of the enantioselectivity depend on the appropriate combination of the substituents on the structural scaffold, but also on the metal-alkoxide involved in the catalysis (zinc or lithium alkoxides). The enantioselective addition of diethylzinc to benzaldehyde mediated by ligands 5a and 5c has been studied with OFT methods. The theoretical evaluation was performed in connection with a working hypothesis based on the different loadings of cis- and trans-catalysts in the reaction medium. (C) 2010 Elsevier Ltd. All rights reserved.
• 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.