(S)-2-<(benzyloxycarbonyl)amino>-2-<(4-methylphenyl)sulfenyl>-3,3,3-trifluoropropanal

• 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: (S)-2-<(benzyloxycarbonyl)amino>-2-<(4-methylphenyl)sulfenyl>-3,3,3-trifluoropropanal
• 英文别名: benzyl N-[(2S)-1,1,1-trifluoro-2-(4-methylphenyl)sulfanyl-3-oxopropan-2-yl]carbamate
• 化学式: C₁₈H₁₆F₃NO₃S
• 分子量: 383.391
• InChiKey: AQESYUSLGHYKHF-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  80.7
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  benzyl N-[(Z)-3,3,3-trifluoro-1-[(R)-(4-methylphenyl)sulfinyl]prop-1-en-2-yl]carbamate 在 水 、 silica gel 作用下， 以 四氢呋喃 为溶剂， 反应 22.02h， 生成 (S)-2-<(benzyloxycarbonyl)amino>-2-<(4-methylphenyl)sulfenyl>-3,3,3-trifluoropropanal
  参考文献：
  名称：

  Synthesis of N-Cbz-fluoropyruvaldehydeN,S-ketals: construction of highly stereoselective and high yielding synthetic reactions using multivariate modelling and design

  摘要：

  The synthesis of (R)-fluoropyruvaldehyde-N,S-ketals via a tandem self-immolative Pummerer-type rearrangement of enantiopure (R)-alpha-fluoroalkyl-beta-sulfinylenamines has been studied using statistical experimental design and multivariate modelling. By this study a procedure has been established which simultaneously gives excellent enantioselectivity and synthetically useful yields. The improvement of the ee of the trifluoro derivative was from 69% to 82%. The optimised procedure has been scaled up (10 fold) and extended to the corresponding difluoro and chlorodifluoro derivatives, with similarly good results. The chemometric analysis, along with a crossover experiment, strongly supports the hypothesis of a strictly intramolecular process, according to the previously proposed mechanism. (C) 1997 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0957-4166(97)00338-8

文献信息

• (<i>R</i>)-Trifluoro- and Difluoropyruvaldehyde <i>N</i>,<i>S</i>-Ketals:  Chiral Synthetic Equivalents of β-Trifluoro and β-Difluoro α-Amino Aldehydes
  作者：Alessandro Volonterio、Barbara Vergani、Marcello Crucianelli、Matteo Zanda、Pierfrancesco Bravo

  DOI：10.1021/jo980602p

  日期：1998.10.1

  A new, efficient, and stereoselective two-step approach to stereochemically defined chiral nonracemic gamma-tri- and gamma-difluoro beta-amino alcohols (70% to >95% ee) is described, using tri- and difluoropyruvaldehyde N,S-ketals (R)-1a,b as starting materials. Addition of Grignard reagents to (R)-1 occurs with moderate to excellent anti-stereocontrol, depending on the nature of the organomagnesium

  描述了一种新的，高效的，立体选择性的两步法，使用三氟和二氟丙酮醛N，S-缩酮对立体化学定义的手性非外消旋γ-三氟和γ-二氟β-氨基醇（70％至> 95％ee）进行了描述（R）-1a，b为起始原料。根据有机卤化镁的性质，将格氏试剂添加到（R）-1时会产生中度至出色的抗立体控制，从而提供β-对甲苯硫基β-苄氧基羰基氨基仲甲醇5。这些反应的立体化学结果可能是通过螯合的克拉姆循环模型合理化，其中NCbz基团是螯合配体，而对甲苯硫基残基充当立体控制“大”基团。通过NaBH（4）/吡啶系统有效地进行5的2-对甲苯硫基取代基的还原置换，很可能是通过相应的中间瞬态亚胺13进行的，从而提供了无硫的γ-三氟和γ-二氟β-具有高抗立体选择性的氨基醇7。通过在相应的苯乙酸酯8上进行反应，获得了向顺-立体选择性的相当大的转变。7的NHCbz部分的裂解和还原分别提供了去氧麻黄碱（11）和麻黄碱（12）的三氟和二氟类似物。
• Synthesis of N-Cbz-fluoropyruvaldehydeN,S-ketals: construction of highly stereoselective and high yielding synthetic reactions using multivariate modelling and design
  作者：Hans-René Bjørsvik、Pierfrancesco Bravo、Marcello Crucianelli、Alessandro Volonterio、Matteo Zanda

  DOI：10.1016/s0957-4166(97)00338-8

  日期：1997.8

  The synthesis of (R)-fluoropyruvaldehyde-N,S-ketals via a tandem self-immolative Pummerer-type rearrangement of enantiopure (R)-alpha-fluoroalkyl-beta-sulfinylenamines has been studied using statistical experimental design and multivariate modelling. By this study a procedure has been established which simultaneously gives excellent enantioselectivity and synthetically useful yields. The improvement of the ee of the trifluoro derivative was from 69% to 82%. The optimised procedure has been scaled up (10 fold) and extended to the corresponding difluoro and chlorodifluoro derivatives, with similarly good results. The chemometric analysis, along with a crossover experiment, strongly supports the hypothesis of a strictly intramolecular process, according to the previously proposed mechanism. (C) 1997 Published by Elsevier Science Ltd.
• Preparation of (<i>R</i>)-Fluoropyruvaldehyde <i>N</i>,<i>S</i>-Ketals by Highly Stereospecific Tandem Pummerer Rearrangement/1,2-<i>p</i>-Tolylthio Group Migration of (<i>R</i>)-α-(Fluoroalkyl)-β-sulfinylenamines
  作者：Alessandro Volonterio、Matteo Zanda、Pierfrancesco Bravo、Giovanni Fronza、Giancarlo Cavicchio、Marcello Crucianelli

  DOI：10.1021/jo970863j

  日期：1997.11.1

  Fluoropyruvaldehyde N,S-ketals (R)-2 have been prepared in good yields (up to 88%) and ee (up to 79%) from alpha-(fluoroalkyl)-beta-sulfinylenamines (R)-(Z)-1, through a new self-immolative tandem sequential process, consisting of a Pummerer reaction, promoted by trifluoroacetic anhydride, followed by a 1,2-migration of the p-tolylthio group, triggered by addition of silica gel or aqueous base. Each transfer of stereogenic center, from sulfur to the alpha-carbon and then to the beta-carbon, occurs with an average degree of enantioselectivity up to 94:6. Cts geometry between the sulfinyl and the amino groups of the starting enamine (R)-1 is necessary for achieving high level of stereocontrol, since neighboring group participation by the N-Cbz amino group prevents the sulfinyl center from racemization promoted by trifluoroacetic anhydride. NMR studies have shown that imines 3 are intermediate products of the Pummerer rearrangement, which are stable in the reaction environment.
• Highly Stereoselective Tandem Pummerer Reaction/α-Hydroxy Imine Rearrangement of E.P. β-Sulfinylenamines
  作者：Pierfrancesco Bravo、Marcello Crucianelli、Alessandro Volonterio、Matteo Zanda

  DOI：10.1080/10426509708545545

  日期：1997.1.1