(S)-N-((R)-1-(dimethylamino)-3-methyl-1-oxobutan-2-yl)-2-isothiocyanato-3,3-dimethylbutanamide | 1003922-09-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-N-((R)-1-(dimethylamino)-3-methyl-1-oxobutan-2-yl)-2-isothiocyanato-3,3-dimethylbutanamide
• 英文别名: (2S)-N-[(2R)-1-(dimethylamino)-3-methyl-1-oxobutan-2-yl]-2-isothiocyanato-3,3-dimethylbutanamide
• CAS: 1003922-09-5
• 化学式: C₁₄H₂₅N₃O₂S
• 分子量: 299.437
• InChiKey: WXNKJQFSALGREA-GHMZBOCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  93.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1R,2R)-N1,N1-二丙基环己烷-1,2-二胺 、 (S)-N-((R)-1-(dimethylamino)-3-methyl-1-oxobutan-2-yl)-2-isothiocyanato-3,3-dimethylbutanamide 以 二氯甲烷 为溶剂， 反应 2.0h， 以437 mg的产率得到(S)-N-((R)-1-(dimethylamino)-3-methyl-1-oxobutan-2-yl)-2-(3-((1R,2R)-2-(dipropylamino)cyclohexyl)thioureido)-3,3-dimethylbutanamide
  参考文献：
  名称：

  Cooperative Catalysis by Tertiary Amino-Thioureas:  Mechanism and Basis for Enantioselectivity of Ketone Cyanosilylation

  摘要：

  The mechanism of the enantioselective cyanosilylation of ketones catalyzed by tertiary aminothiourea derivatives was investigated using a combination of experimental and theoretical methods. The kinetic analysis is consistent with a cooperative mechanism in which both the thiourea and the tertiary amine of the catalyst are involved productively in the rate-limiting cyanide addition step. Density functional theory calculations were used to distinguish between mechanisms involving thiourea activation of ketone or of cyanide in the enantioselectivity-determining step. The strong correlation obtained between experimental and calculated ee's for a range of substrates and catalysts provides support for the most favorable calculated transition structures involving amine-bound HCN adding to thiourea-bound ketone. The calculations suggest that enantioselectivity arises from direct interactions between the ketone substrate and the amino-acid derived portion of the catalyst. On the basis of this insight, more enantioselective catalysts with broader substrate scope were prepared and evaluated experimentally.

  DOI：

  10.1021/ja0735352
• 作为产物：
  描述：

  硫光气 、 在 碳酸氢钠 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 (S)-N-((R)-1-(dimethylamino)-3-methyl-1-oxobutan-2-yl)-2-isothiocyanato-3,3-dimethylbutanamide
  参考文献：
  名称：

  Cooperative Catalysis by Tertiary Amino-Thioureas:  Mechanism and Basis for Enantioselectivity of Ketone Cyanosilylation

  摘要：

  The mechanism of the enantioselective cyanosilylation of ketones catalyzed by tertiary aminothiourea derivatives was investigated using a combination of experimental and theoretical methods. The kinetic analysis is consistent with a cooperative mechanism in which both the thiourea and the tertiary amine of the catalyst are involved productively in the rate-limiting cyanide addition step. Density functional theory calculations were used to distinguish between mechanisms involving thiourea activation of ketone or of cyanide in the enantioselectivity-determining step. The strong correlation obtained between experimental and calculated ee's for a range of substrates and catalysts provides support for the most favorable calculated transition structures involving amine-bound HCN adding to thiourea-bound ketone. The calculations suggest that enantioselectivity arises from direct interactions between the ketone substrate and the amino-acid derived portion of the catalyst. On the basis of this insight, more enantioselective catalysts with broader substrate scope were prepared and evaluated experimentally.

  DOI：

  10.1021/ja0735352

文献信息

• Chiral thiourea compounds and process for enantioselective reduction of ketones
  申请人：Li Derun

  公开号：US20090253919A1

  公开（公告）日：2009-10-08

  Chiral thioureas are effective catalysts for the borane reduction of prochiral ketones to optically active alcohols. A prochiral ketone may be reduced to an optically active alcohol in the presence of a substantially sub-stoichiometric amount of chiral thiourea. The asymmetric thiourea compound of the present invention may be produced according to a production method described herein.

  手性硫脲是对丙酮进行硼氢化还原生成光学活性醇的有效催化剂。在存在明显亚化学计量量手性硫脲的情况下，可以将一个丙酮还原为光学活性醇。本发明的不对称硫脲化合物可以根据本文描述的生产方法制备。
• Enantioselective, Organocatalytic Reduction of Ketones using Bifunctional Thiourea-Amine Catalysts
  作者：De Run Li、Anyu He、J. R. Falck

  DOI：10.1021/ol100365c

  日期：2010.4.16

  Prochiral ketones are reduced to enantioenriched, secondary alcohols using catecholborane and a family of air-stable, bifunctional thiourea amine organocatalysts. Asymmetric induction is proposed to arise from the in situ complexation between the borane and chiral thiourea amine organocatalyst resulting in a stereochemically biased boronate amine complex. The hydride in the complex is endowed with enhanced nucleophilicity while the thiourea concomitantly embraces and activates the carbonyl.
• US8334405B2
  申请人：——

  公开号：US8334405B2

  公开（公告）日：2012-12-18
• Cooperative Catalysis by Tertiary Amino-Thioureas:  Mechanism and Basis for Enantioselectivity of Ketone Cyanosilylation
  作者：Stephan J. Zuend、Eric N. Jacobsen

  DOI：10.1021/ja0735352

  日期：2007.12.1

  The mechanism of the enantioselective cyanosilylation of ketones catalyzed by tertiary aminothiourea derivatives was investigated using a combination of experimental and theoretical methods. The kinetic analysis is consistent with a cooperative mechanism in which both the thiourea and the tertiary amine of the catalyst are involved productively in the rate-limiting cyanide addition step. Density functional theory calculations were used to distinguish between mechanisms involving thiourea activation of ketone or of cyanide in the enantioselectivity-determining step. The strong correlation obtained between experimental and calculated ee's for a range of substrates and catalysts provides support for the most favorable calculated transition structures involving amine-bound HCN adding to thiourea-bound ketone. The calculations suggest that enantioselectivity arises from direct interactions between the ketone substrate and the amino-acid derived portion of the catalyst. On the basis of this insight, more enantioselective catalysts with broader substrate scope were prepared and evaluated experimentally.