(2R,1'R)-N-tert-butoxy-N-1'-(1''-naphthyl)ethyl 2-benzylpropanamide | 1177266-25-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (2R,1'R)-N-tert-butoxy-N-1'-(1''-naphthyl)ethyl 2-benzylpropanamide
• 英文别名: (2R)-2-methyl-N-[(2-methylpropan-2-yl)oxy]-N-[(1R)-1-naphthalen-1-ylethyl]-3-phenylpropanamide
• CAS: 1177266-25-9
• 化学式: C₂₆H₃₁NO₂
• 分子量: 389.538
• InChiKey: VMTFTQLDGSGEHE-WOJBJXKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 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：

  (2R,1'R)-N-tert-butoxy-N-1'-(1''-naphthyl)ethyl 2-benzylpropanamide 、 甲基锂 以 乙醚 为溶剂， 以74%的产率得到(R)-3-methyl-4-phenylbutan-2-one
  参考文献：
  名称：

  The Chiral Auxiliary N-1-(1′-Naphthyl)ethyl-O-tert-butylhydroxylamine: A Chiral Weinreb Amide Equivalent

  摘要：

  The chiral auxiliary N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxylamine is readily prepared from N-hydroxyphthalimide in four steps, with resolution giving access to both enantiomers in >98% ee, on a multigram (>25 g) scale. Conversion to a range of N-acyl derivatives, followed by highly diastereoselective alkylation (>= 94% de) gives the corresponding chiral, 2-substituted derivatives as single diastereoisomers (>98% de) after chromatography. Reductive cleavage with LlAlH(4) allows direct access to chiral aldehydes, and treatment with MeLi gives chiral methyl ketones in excellent enantiopurity (>= 94% ee). The auxiliary can be recovered in >98% ee and recycled.

  DOI：

  10.1021/ol901174t
• 作为产物：
  描述：

  (R)-N-tert-butoxy-N-1'-(1''-naphthyl)ethyl 3-phenylpropanamide 、 碘甲烷 在 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 以85%的产率得到(2R,1'R)-N-tert-butoxy-N-1'-(1''-naphthyl)ethyl 2-benzylpropanamide
  参考文献：
  名称：

  The Chiral Auxiliary N-1-(1′-Naphthyl)ethyl-O-tert-butylhydroxylamine: A Chiral Weinreb Amide Equivalent

  摘要：

  The chiral auxiliary N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxylamine is readily prepared from N-hydroxyphthalimide in four steps, with resolution giving access to both enantiomers in >98% ee, on a multigram (>25 g) scale. Conversion to a range of N-acyl derivatives, followed by highly diastereoselective alkylation (>= 94% de) gives the corresponding chiral, 2-substituted derivatives as single diastereoisomers (>98% de) after chromatography. Reductive cleavage with LlAlH(4) allows direct access to chiral aldehydes, and treatment with MeLi gives chiral methyl ketones in excellent enantiopurity (>= 94% ee). The auxiliary can be recovered in >98% ee and recycled.

  DOI：

  10.1021/ol901174t

文献信息

• On the Origins of Diastereoselectivity in the Alkylation of Enolates Derived from <i>N</i>-1-(1′-Naphthyl)ethyl-<i>O</i>-<i>tert</i>-butylhydroxamates: Chiral Weinreb Amide Equivalents
  作者：Stephen G. Davies、Christopher J. Goodwin、David Hepworth、Paul M. Roberts、James E. Thomson

  DOI：10.1021/jo902499s

  日期：2010.2.19

  The stereochemical outcome observed upon alkylation of enolates derived from N-1-(1′-naphthyl)ethyl-O-tert-butylhydroxamates (chiral Weinreb amide equivalents) may be rationalized by a chiral relay mechanism. Deprotonation with KHMDS leads to a nonchelated (Z)-enolate in which the oxygen atoms adopt an anti-periplanar conformation. The configuration of the N-1-(1′-naphthyl)ethyl group dictates the

  的立体化学结果在从衍生的烯醇化物烷基化观察Ñ -1-（1'-萘基）乙基- ø -叔-butylhydroxamates（手性Weinreb酰胺等同物）可以通过手性继电器机构合理化。用KHMDS进行去质子化反应会生成非螯合的（Z）-烯醇酸酯，其中氧原子采用反周平面构象。所述的配置Ñ -1-（1'-萘基）乙基使然的的构象ø -叔丁基团和由相邻的棱锥形的氮原子通过的结构。高度非对映烯醇烷基化然后进行抗既笨重的叔-丁基（空间驱动）和N-孤对（空间电子驱动）。
• The Chiral Auxiliary <i>N</i>-1-(1′-Naphthyl)ethyl-<i>O</i>-<i>tert</i>-butylhydroxylamine: A Chiral Weinreb Amide Equivalent
  作者：Alexander N. Chernega、Stephen G. Davies、Christopher J. Goodwin、David Hepworth、Wataru Kurosawa、Paul M. Roberts、James E. Thomson

  DOI：10.1021/ol901174t

  日期：2009.8.6

  The chiral auxiliary N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxylamine is readily prepared from N-hydroxyphthalimide in four steps, with resolution giving access to both enantiomers in >98% ee, on a multigram (>25 g) scale. Conversion to a range of N-acyl derivatives, followed by highly diastereoselective alkylation (>= 94% de) gives the corresponding chiral, 2-substituted derivatives as single diastereoisomers (>98% de) after chromatography. Reductive cleavage with LlAlH(4) allows direct access to chiral aldehydes, and treatment with MeLi gives chiral methyl ketones in excellent enantiopurity (>= 94% ee). The auxiliary can be recovered in >98% ee and recycled.