(2S)-2-[(methoxymethoxy)methyl]pyrrolidine | 130563-28-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (2S)-2-[(methoxymethoxy)methyl]pyrrolidine
• 英文别名: (S)-2-<<(methoxymethyl)oxy>methyl>pyrrolidine；(S)-2-methoxymethoxymethyl-pyrrolidine；(2S)-2-(methoxymethoxymethyl)pyrrolidine
• CAS: 130563-28-9
• 化学式: C₇H₁₅NO₂
• 分子量: 145.202
• InChiKey: DUIITDAJVYZQBP-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S)-2-[(methoxymethoxy)methyl]pyrrolidine 在 lithium bromide 作用下， 以 乙腈 为溶剂， 反应 25.17h， 生成 3-Butyl-2-((S)-2-methoxymethoxymethyl-pyrrolidin-1-ylmethyl)-cyclopentanone
  参考文献：
  名称：

  Asymmetric synthesis of 3-substituted 2-exo-methylenealkanones by addition-elimination reaction using a chiral leaving group and organometallic nucleophiles

  摘要：

  A novel diastereodifferentiating addition-elimination reaction of (S)-2-[[2-(methoxymethyl)-1-pyrrolidinyl]methyl]-2-alken-1-ones with organometallic reagents such as organocuprates and organozincates afforded optically active 3-substituted 2-methylenealkanones with high enantiomeric purity. The enantiomeric excess (ee) of the products in this asymmetric induction reaction involving 1,5-transfer of stereogenicity was highly dependent on the structure of the enone substrates and the type of organometallic reagents, chiral auxiliaries, and added Lewis acids: (i) the use of lithium diorganocuprates (R2CuLi) led to the highest ee's, (ii) in the reaction with R2CuLi the ee decreased in the following order by varying their structure of the main framework of the enones, cycloheptenones (96-97% ee) > cyclohexenones (95% ee) > cyclopentenones (82-85% ee) > acyclic enones (55-70% ee), (iii) the addition of LiBr as the external Lewis acid in the reaction with R2CuLi did not affect the ee, whereas that of ZnBr2 or MgBr2 decreased the ee by 5% or considerably more, respectively, and (iv) the existence of the methoxy oxygen atom in the chiral auxiliary was essential to achieve high ee's. The origin of the observed high and low ee's was rationalized by considering plausible transition state models.

  DOI：

  10.1021/jo00044a026
• 作为产物：
  描述：

  L-脯氨酸 在 dimethyl sulfide borane 、 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 16.0h， 生成 (2S)-2-[(methoxymethoxy)methyl]pyrrolidine
  参考文献：
  名称：

  概念驱动的脯氨醇化学选择性 O/N 衍生化：获取有机催化剂的直线方法

  摘要：

  已报道了对反应条件对高度利用的方案的敏感性的研究，其中可以控制脯氨醇的单 Boc 官能化以专门合成N -Boc、O -Boc 或恶唑烷酮衍生物。机理研究表明，基本步骤可能由以下因素控制：（a）识别不同酸性位点（NH和OH）所需的碱，以形成与亲电子试剂反应的共轭碱，以及（b）缀合物碱性位点的亲核性。在此，报道了通过使用合适的碱对脯氨醇的亲核位点进行成功的化学选择性功能化。这是通过利用 NH 和 OH 的相对酸度差异以及相应共轭碱基 N -和 O -的反向亲核性来实现的。该方案也已用于合成几种O-功能化脯氨醇衍生的有机催化剂，其中很少有新报道。

  DOI：

  10.1021/acs.joc.3c00992

文献信息

• Further Application of an N-Ar Axially Chiral Mimetic-Type Ligand: Asymmetric Grignard Cross-Coupling Reaction
  作者：Kazuhiro Kondo、Toyohiko Aoyama、Hideo Horibe、Kumiko Kazuta、Minori Kotoku、Hiroaki Okuno、Yasuoki Murakami

  DOI：10.1055/s-2003-41485

  日期：——

  A novel chiral ligand mimicking N-Ar axial chirality, (S)-N-[2-(diphenylphosphanyl)naphthalen-1-yl]-2-(piperidinyl­meth­yl)piperidine, was found to exhibit good enantioselectivity (up to 80% ee) in the asymmetric cross-coupling reaction of 1-phenyl­ethylmagnesium chloride with β-bromostyrene derivatives. Additionall­y, this type ligand is appealing, because it allows the synthesis of a wide variety of analogues.

  一种新型手性配体，模拟N-Ar轴向手性，(S)-N-[2-(二苯膦基)萘-1-基]-2-(哌啶基甲基)哌啶，在1-苯乙基氯化镁与β-溴苯乙烯衍生物的不对称交叉偶联反应中显示出良好的对映选择性（高达80% ee）。此外，这种类型的配体具有吸引力，因为它允许合成多种多样的类似物。
• Asymmetric Kumada–Corriu cross-coupling reaction with Pd2(dba)3 and an N–Ar axially chiral mimetic-type ligand catalyst
  作者：Hideo Horibe、Yoshimasa Fukuda、Kazuhiro Kondo、Hiroaki Okuno、Yasuoki Murakami、Toyohiko Aoyama

  DOI：10.1016/j.tet.2004.09.010

  日期：2004.11

  aryl bromide groups, the chemoselective asymmetric cross-coupling reaction of the vinyl bromide group is observed. This N–Ar axially chiral mimetic-type ligand allows easy synthesis of a wide variety of analogues, and starting from the initial ligand, the enantioselectivity of coupling products is improved by modifying the structure in the ligand.

  一种由Pd 2（dba）3 ·CHCl 3和N–Ar轴向手性模拟型配体（S）-N- [2-（二苯基膦基）萘-1-基] -2-（哌啶基甲基）哌啶组成的催化剂，为1-苯基乙基氯化镁与E的不对称Kumada-Corriu交叉偶联反应提供了良好的对映选择性-β-溴苯乙烯衍生物，用它很难实现高对映选择性。此外，在同时带有乙烯基和芳基溴化物基团的苯乙烯衍生物的情况下，观察到乙烯基溴化物基团的化学选择性不对称的交叉偶联反应。这种N–Ar轴向手性模拟型配体可轻松合成多种类似物，并且从初始配体开始，通过修饰配体中的结构可改善偶联产物的对映选择性。
• Investigation of the asymmetric Birch reduction–alkylation of a chiral 5-arylbenzamide containing a carbamate group
  作者：Agustin Casimiro-Garcia、Arthur G. Schultz

  DOI：10.1016/j.tetlet.2006.02.093

  日期：2006.4

  The synthesis and asymmetric Birch reduction–alkylation of chiral benzamide 17 are described. Birch reductive alkylation of benzamide 17 was optimized to give the corresponding cyclohexa-1,4-diene products in 66–78% isolated yield and with high diastereoselectivity (dr: >98:2). The effects of performing the reduction in the presence and in the absence of tert-butyl alcohol are discussed.

  描述了手性苯甲酰胺17的合成和不对称的桦木还原-烷基化。优化了苯甲酰胺17的桦木还原烷基化反应，以66-78％的分离产率和高非对映选择性（dr：> 98：2）得到了相应的环己-1,4-二烯产物。讨论了在存在和不存在叔丁醇的情况下进行还原的效果。
• Asymmetric Synthesis of -Substituted N-Methylsulfonamides
  作者：Dieter Enders、Christian R. Thomas、Nicola Vignola、Gerhard Raabe

  DOI：10.1002/1522-2675(200211)85:11<3657::aid-hlca3657>3.0.co;2-a

  日期：2002.11

  A novel amine auxiliary for the asymmetric synthesis of a-substituted N-methylsulfonamides is described. The reaction of 4-([1,1'-biphenyl]-4-yl)-2,2-dimethyl-1,3-dioxan-5-amine (16) with various aliphatic sulfonyl chlorides afforded the corresponding sulfonamides, which were lithiated and subsequently reacted with electrophiles to give the corresponding products in high yields and good-to-excellent asymmetric inductions (de 83-95%). Racemization-free cleavage of the auxiliary led to the a-alkylated N-methylsulfonamides in acceptable yields and high enantiomer purities (ee 91 to greater than or equal to 98).
• KAWANAMI, YASUHIRO;KATSUKI, TSUTOMU;YAMAGUCHI, BULL. CHEM. SOC. JAP., 60,(1987) N 11, 4190-4192
  作者：KAWANAMI, YASUHIRO、KATSUKI, TSUTOMU、YAMAGUCHI

  DOI：——

  日期：——