methyl 4,6-O-benzylidene-2-O-diazoacetyl-3-O-pivaloyl-α-D-mannopyranoside | 1256137-13-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃二恶英
• 英文名称: methyl 4,6-O-benzylidene-2-O-diazoacetyl-3-O-pivaloyl-α-D-mannopyranoside
• 英文别名: [(2R,4aR,6S,7S,8S,8aR)-7-(2-diazoacetyl)oxy-6-methoxy-2-phenyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-8-yl] 2,2-dimethylpropanoate
• CAS: 1256137-13-9
• 化学式: C₂₁H₂₆N₂O₈
• 分子量: 434.446
• InChiKey: KQPBLEGDRFPHFF-XFMWHNAVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  91.5
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  methyl 4,6-O-benzylidene-2-O-diazoacetyl-3-O-pivaloyl-α-D-mannopyranoside 在 dirhodium tetraacetate 、 重水 、 potassium carbonate 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  碳介导的CH键官能化中的电子效应：实验和理论研究

  摘要：

  AbstractIn this article, we show that short‐distance and long‐range electronic effects are strongly affecting the mechanism and stereoselectivity of Rh(II)‐carbene mediated CH functionalization processes. Based on experimental studies with deuterium‐labelled carbohydrates and DFT calculations, we show that the orientation of the lone pairs of adjacent heteroatoms, as well as the nature of substituents located far from the reaction center, are inducing a shift from the classical concerted mechanism to the less common stepwise process. Furthermore, we reveal that the stereochemical outcome of these transformations is depending on the relative energies of the CH bond activation and Rh(II)‐carbene isomerization barriers. The formation of a single diastereoisomer is thus resulting from Curtin–Hammet‐like kinetics when insertion occurs in poorly activated CH bonds. However, the formation of diastereoisomeric mixtures is resulting from two disconnected and totally stereoselective transformations when the reactivity of the CH bonds towards electrophilic metallocarbenes is increased by short‐distance or long‐range electronic effects.Abbreviations: Rh: rhodium; Bn: benzyl; Bz: benzoyl; Me: methyl; t‐Bu: tert‐butyl; Ph: phenyl; Ac: acetyl; ClAc: chloroacetyl; TBDMS: tert‐butyldimethylsilyl; TMS: trimethylsilyl; D: deuterium; P: protecting group; L: ligand; THF: tetrahydrofuran; DFT: density functional theory; TS: transition state; BO: bond order; NMR: nuclear magnetic resonance; MS: mass spectrometry; NOE: nuclear Overhauser effect.magnified image

  DOI：

  10.1002/adsc.201300984
• 作为产物：
  描述：

  methyl 4,6-O-benzylidene-3-O-pivaloyl-α-D-mannopyranoside 在 吡啶 、 N,N′-双(对甲苯磺酰)肼 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 0.42h， 生成 methyl 4,6-O-benzylidene-2-O-diazoacetyl-3-O-pivaloyl-α-D-mannopyranoside
  参考文献：
  名称：

  碳烯介导的端粒C ？官能化？碳水化合物的氢键：范围和局限性

  摘要：

  在此，我们对调查α-，β-ketopyranosides依靠异头C的官能一种新的合成方法的范围和局限性通过插入金属卡宾来实现碳水化合物的H键。在2位接枝的关键溴乙酸盐是立体选择性糖基化/重氮转移/季铵化序列的基石，这使得在完全控制立体化学的情况下构建季中心成为可能。该序列显示出对碳水化合物化学中常用的保护基的良好耐受性，并以良好的效率产生了季二糖。在具有更受限构象的二糖的情况下，该功能化过程可能会受到目标异头异构体位置旁边的空间需求的阻碍。另外，在糖基化步骤期间形成瞬时原酸酯也可能降低合成序列的整体效率。

  DOI：

  10.1002/chem.201203725

文献信息

• Rh(II) Carbene-Promoted Activation of the Anomeric C−H Bond of Carbohydrates: A Stereospecific Entry toward α- and β-Ketopyranosides
  作者：Mélissa Boultadakis-Arapinis、Pascale Lemoine、Serge Turcaud、Laurent Micouin、Thomas Lecourt

  DOI：10.1021/ja1054065

  日期：2010.11.10

  In this communication we report a new strategy toward ketopyranosides based on a carbene-mediated activation of the anomeric C-H bond of carbohydrates. By forming a new carbon-carbon bond after a glycosylation step, this approach enables the preparation of both alpha- and beta-ketopyranosides from advanced precursors.
• Rh(II) Carbene-Mediated Synthesis of Methyl α- and β-Ketopyranosides: Preparation of Carbene Precursors, Quaternarization of the Anomeric Position, and Ring Opening of γ-Lactones
  作者：Mélissa Boultadakis-Arapinis、Camille Lescot、Laurent Micouin、Thomas Lecourt

  DOI：10.1080/07328303.2011.614983

  日期：2011.9.1

  Methyl alpha- and beta-ketopyranosides were efficiently prepared by carbene-mediated quaternarization of the anomeric position of corresponding aldopyranosides. Preparation of carbene precursors proved to be tedious and required a two-step procedure involving first bromoacetylation, followed by diazo-transfer with N,N'-ditosylhydrazine and DBU. Selective functionalization of the anomeric C-H bond was then achieved under Rh-2(OAc)(4) or Rh-2(acam)(4) catalysis. Finally, ring opening of the resulting gamma-lactones delivered alpha- and beta-ketopyranosides with the anomeric position functionalized by an independent chain.
• Gram-Scale Quaternarization of the Anomeric Position of Carbohydrates: Dramatic Effects of Molecular Sieves on Rhodium(II)-Mediated Decomposi­tion of Diazo Sugars
  作者：Thomas Lecourt、Mélissa Boultadakis-Arapinis、Camille Lescot、Laurent Micouin

  DOI：10.1055/s-0032-1317013

  日期：——

  The optimization of rhodium(II) carbene mediated quaternarization of the anomeric position of carbohydrates is reported. Preparation of ketopyranosides in good and reliable yields requires reverse addition of the substrate to a highly diluted suspension of the catalyst in refluxing 1,2-dichloroethane, as well as addition of a carefully controlled amount of molecular sieves, and vigorous stirring. Following these optimized reaction conditions, functionalization of the anomeric position of carbohydrates can finally be performed on a preparative scale.
• Carbene-Mediated Functionalization of the Anomeric CH Bond of Carbohydrates: Scope and Limitations
  作者：Mélissa Boultadakis-Arapinis、Elise Prost、Vincent Gandon、Pascale Lemoine、Serge Turcaud、Laurent Micouin、Thomas Lecourt

  DOI：10.1002/chem.201203725

  日期：2013.5.3

  Herein we investigate the scope and limitations of a new synthetic approach towards α‐ and β‐ketopyranosides relying on the functionalization of the anomeric CH bond of carbohydrates by insertion of a metal carbene. A key bromoacetate grafted at the 2‐position is the cornerstone of a stereoselective glycosylation/diazotransfer/quaternarization sequence that makes possible the construction of a quaternary

  在此，我们对调查α-，β-ketopyranosides依靠异头C的官能一种新的合成方法的范围和局限性通过插入金属卡宾来实现碳水化合物的H键。在2位接枝的关键溴乙酸盐是立体选择性糖基化/重氮转移/季铵化序列的基石，这使得在完全控制立体化学的情况下构建季中心成为可能。该序列显示出对碳水化合物化学中常用的保护基的良好耐受性，并以良好的效率产生了季二糖。在具有更受限构象的二糖的情况下，该功能化过程可能会受到目标异头异构体位置旁边的空间需求的阻碍。另外，在糖基化步骤期间形成瞬时原酸酯也可能降低合成序列的整体效率。
• Electronic Effects in Carbene-Mediated CH Bond Functionalization: An Experimental and Theoretical Study
  作者：Mélissa Boultadakis-Arapinis、Vincent Gandon、Elise Prost、Laurent Micouin、Thomas Lecourt

  DOI：10.1002/adsc.201300984

  日期：2014.8.11

  AbstractIn this article, we show that short‐distance and long‐range electronic effects are strongly affecting the mechanism and stereoselectivity of Rh(II)‐carbene mediated CH functionalization processes. Based on experimental studies with deuterium‐labelled carbohydrates and DFT calculations, we show that the orientation of the lone pairs of adjacent heteroatoms, as well as the nature of substituents located far from the reaction center, are inducing a shift from the classical concerted mechanism to the less common stepwise process. Furthermore, we reveal that the stereochemical outcome of these transformations is depending on the relative energies of the CH bond activation and Rh(II)‐carbene isomerization barriers. The formation of a single diastereoisomer is thus resulting from Curtin–Hammet‐like kinetics when insertion occurs in poorly activated CH bonds. However, the formation of diastereoisomeric mixtures is resulting from two disconnected and totally stereoselective transformations when the reactivity of the CH bonds towards electrophilic metallocarbenes is increased by short‐distance or long‐range electronic effects.Abbreviations: Rh: rhodium; Bn: benzyl; Bz: benzoyl; Me: methyl; t‐Bu: tert‐butyl; Ph: phenyl; Ac: acetyl; ClAc: chloroacetyl; TBDMS: tert‐butyldimethylsilyl; TMS: trimethylsilyl; D: deuterium; P: protecting group; L: ligand; THF: tetrahydrofuran; DFT: density functional theory; TS: transition state; BO: bond order; NMR: nuclear magnetic resonance; MS: mass spectrometry; NOE: nuclear Overhauser effect.magnified image