benzyl N-[(Z)-3,3-difluoro-1-[(R)-(4-methylphenyl)sulfinyl]prop-1-en-2-yl]carbamate | 169138-10-7

• 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: benzyl N-[(Z)-3,3-difluoro-1-[(R)-(4-methylphenyl)sulfinyl]prop-1-en-2-yl]carbamate
• CAS: 169138-10-7
• 化学式: C₁₈H₁₇F₂NO₃S
• 分子量: 365.401
• InChiKey: KHCWWATYVOCELR-UJFTWNBESA-N

物化性质

• 沸点：
  542.0±50.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  74.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  benzyl N-[(Z)-3,3-difluoro-1-[(R)-(4-methylphenyl)sulfinyl]prop-1-en-2-yl]carbamate 在 乙酰氯 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以90%的产率得到
  参考文献：
  名称：

  Preparation of (R)-Fluoropyruvaldehyde N,S-Ketals by Highly Stereospecific Tandem Pummerer Rearrangement/1,2-p-Tolylthio Group Migration of (R)-α-(Fluoroalkyl)-β-sulfinylenamines

  摘要：

  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.

  DOI：

  10.1021/jo970863j
• 作为产物：
  描述：

  N-Cbz-triphenyliminophosphorane 在 sodium hydride 、 氯甲酸苄酯 作用下， 以 苯 为溶剂， 反应 18.08h， 生成 benzyl N-[(Z)-3,3-difluoro-1-[(R)-(4-methylphenyl)sulfinyl]prop-1-en-2-yl]carbamate
  参考文献：
  名称：

  New Versatile Fluorinated Chiral Building Blocks:  Synthesis and Reactivity of Optically Pure α-(Fluoroalkyl)-β-sulfinylenamines

  摘要：

  Efficient synthesis of optically pure alpha-(fluoroalkyl)-beta-sulfinyl enamines has been achieved by aza-Wittig reaction of triphenyliminophosphoranes with the corresponding alpha-fluorinated-alpha'-sulfinyl ketones. The title compounds 3,4 showed an overwhelming preference for the Z stereochemistry of the enamine form. Their general reactivity has been studied. The reaction with some electrophiles (i.e. benzyl chloroformate and benzyl and allyl bromide) occurs at the nitrogen atom providing the corresponding N,N-disubstituted enamines. Nucleophiles add smoothly to C-2: heteroatom-centered nucleophiles like methanol, ammonia, and thiophenol afford gem-disubstituted derivatives under thermodynamic control, while a C-centered nucleophile like nitromethane adds in irreversible fashion. The hydride- and deuteride-promoted reduction of 3,4 to the N-Cbz-protected (14) and N-unprotected (15) alpha-fluorinated-alpha'-sulfinyl amines has been studied. Hydride addition was stereoselective, while low stereoselection was obtained with the other tested nucleophiles. Desulfurization of the optically pure 1,1,1-trifluoro-3-sulfinyl amine 15a afforded (R)-1-(trifluoromethyl)ethylamine 17. The Pummerer rearrangement of 14 occurs in an unusual nonoxidative way affording the sulfenamide 24, that readily provided (R)-(2-H)- and -(2-D)-3,3,3-trifluoroalaninol (19) and (R)-3,3,3-trifluoroalanine (22).

  DOI：

  10.1021/jo952097r

文献信息

• Stereoselective synthesis of optically pure γ-fluoro-β-enaminosulfoxides and reduction to γ-fluoro-β-aminosulfoxides
  作者：Pierfrancesco Bravo、Marcello Crucianelli、Matteo Zanda

  DOI：10.1016/0040-4039(95)00422-9

  日期：1995.4

  The aza-Wittig reaction of phospha-λ5-azenes with optically pure γ-fluorosubstituted β-ketosulfoxides leads to the corresponding β-enaminosulfoxides, which were easily isolated in diastereomerically pure form. The stereoselective reduction of the enamine 3cb afforded the optically pure β-sulphinyl-amine 5cb in high overall yield.

  phospha-的氮杂Wittig反应λ 5 -azenes与光学纯γ-β氟取代的- ketosulfoxides通向相应β-enaminosulfoxides，将其容易地在对映异构纯形式分离。烯胺3cb的立体选择性还原以高的总收率提供了光学纯的β-亚磺酰基胺5cb。
• (<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.
• 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
• Enantiomerically pure α-fluoroalkyl-α-amino acids: Synthesis of (R)-α-difluoromethyl-alanine and (S)-α-difluoromethyl-serine
  作者：Pierfrancesco Bravo、Silvia Capelli、Stefano V Meille、Paolo Seresini、Alessandro Volonterio、Matteo Zanda

  DOI：10.1016/0957-4166(96)00287-x

  日期：1996.8

  Hydrocyanation of enantiomerically pure N-Cbz alpha-fluoroalkyl beta-sulfinylenamines 1 occurs smoothly by treatment with KCN or by addition of trimethylsilylcyanide or diethyl phosphorocyanidate to preformed sodium derivatives of 1. The diastereoisomeric difluoro alpha-aminonitriles 2b have been transformed in the unnatural amino acids (R)-alpha-difluoromethyl-alanine and (S)-alpha-difluoromethyl-serine. Copyright (C) 1996 Elsevier Science Ltd