(R)-2,2-pentamethylene-4-(p-tolylsulfinyl)methyl-2,5-dihydroixazole | 146860-26-6

• 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: (R)-2,2-pentamethylene-4-(p-tolylsulfinyl)methyl-2,5-dihydroixazole
• 英文别名: (R)-2,2-pentamethylene-4-(p-tolylsulfinyl)methyl-2,5-dihydrooxazol；(+)-(R_S)-3-{[(4-methylphenyl)sulfinyl]methyl}-1-oxa-4-azaspiro[4.5]dec-3-ene；(R_S)-(+)-{[(4-methylphenyl)sulfinyl]methyl}-1-oxa-4-azaspiro[4.5]dec-3-ene；3-[[(R)-(4-methylphenyl)sulfinyl]methyl]-1-oxa-4-azaspiro[4.5]dec-3-ene
• CAS: 146860-26-6
• 化学式: C₁₆H₂₁NO₂S
• 分子量: 291.414
• InChiKey: GAGNJJMJRVNSCC-HXUWFJFHSA-N

物化性质

• 沸点：
  476.7±45.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  57.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)-2,2-pentamethylene-4-(p-tolylsulfinyl)methyl-2,5-dihydroixazole 在 W-2 Raney Ni 正丁基锂 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 (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：

  Sulfoxide-mediated diastereoselective Michael additions. New enantioselective synthesis of C-4 substituted 2-pyroaminoadipic acids

  摘要：

  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.

  DOI：

  10.1016/s0040-4039(99)01047-3
• 作为产物：
  描述：

  4-methyl-2,2-pentamethylene-2,5-dihydrooxazole 、 (-)-(S_S)-menthyl p-toluenesulfinate 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以86%的产率得到(R)-2,2-pentamethylene-4-(p-tolylsulfinyl)methyl-2,5-dihydroixazole
  参考文献：
  名称：

  Stereoselective cyanosilylation of α-sulfinylketimines or its covalently stabilized enamine tautomers. Synthesis of enantiomerically pure α-sulfinylmethyl-α-amino nitriles

  摘要：

  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.

  DOI：

  10.1016/s0040-4020(02)00234-x

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。
• A new approach to vinyl glycine derivatives from (+)-(RS)-3-[(p-toluenesulfinyl)methyl]-1-oxa-4-azaspiro[4,5]decen-3-ene
  作者：Hassan Acherki、Carlos Alvarez-Ibarra、Gonzalo García-Navazo、Elena Gómez-Sánchez、María L. Quiroga-Feijóo

  DOI：10.1016/j.tetasy.2004.09.010

  日期：2004.11

  The diastereoselective reduction of α-benzyl-α-sulfinylketimine 1a with DIBAL–H/ZnCl2, LiEt3BH, and NaCNBH3/AcOH–TFA has been studied. Under the first conditions, the reaction was completely stereoselective and the sulfinyl group involving the formation of a chelated complex with the metallic ion became the sole chiral controller, regardless of the presence of the α-stereocentre. The title compound

  研究了用DIBAL–H / ZnCl 2，LiEt 3 BH和NaCNBH 3 / AcOH–TFA对α-苄基-α-亚磺酰基酮亚胺1a的非对映选择性还原。在第一种条件下，该反应是完全立体选择性的，并且与α-立体异构体的存在无关，涉及与金属离子形成螯合配合物的亚磺酰基成为唯一的手性控制剂。标题化合物6-I被衍生为环状氨基甲酸酯2，并且该化合物的碱诱导的脱亚磺酰化使得可以合成对映体纯的N，O-保护的N-环己基-1,2-氨基醇3 具有完全的区域控制和立体声控制。
• 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.
• Total diastereoselectivity in the one-pot multistep reaction of (RS)-(+)-{[(4-methylphenyl)sulfinyl]methyl}-1-oxa-4-azaspiro[4.5]dec-3-ene and E-methyl cinnamate. An approach to (2S,4S,5R,6R)-2-(hydroxymethyl)-4,6-diphenyl-1-azabicycle[3.3.1]nonane
  作者：Carlos Alvarez-Ibarra、Juan F. Collados Luján、Maria L. Quiroga-Feijóo、Gonzalo Rodríguez

  DOI：10.1016/j.tetasy.2008.05.030

  日期：2008.6

  The base-mediated reaction of enantiomerically pure alpha-sulfinylketimine (+)-1 with (E)-methyl cinnamate afforded (+)-5a in a one-pot procedure with complete diastereoselectivity. A sole diastereomer of the eight possible ones was isolated which revealed the stereocantrol of the chiral sulfinyl group in the construction of the three new stereogenic centres. The absolute configuration of stereocentres introduced in (+)-5a was assigned on the basis of H-1 NMR data and a single X-ray structure. (C) 2008 Elsevier Ltd. All rights reserved.