(R)-3,5-Dichloro-N-(2-(4-isopropyl-4,5-dihydrooxazol-2-yl)-6-methoxyphenyl)benzenesulfonamide | 1192815-61-4

• 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: (R)-3,5-Dichloro-N-(2-(4-isopropyl-4,5-dihydrooxazol-2-yl)-6-methoxyphenyl)benzenesulfonamide
• 英文别名: 3,5-dichloro-N-[2-methoxy-6-[(4R)-4-propan-2-yl-4,5-dihydro-1,3-oxazol-2-yl]phenyl]benzenesulfonamide
• CAS: 1192815-61-4
• 化学式: C₁₉H₂₀Cl₂N₂O₄S
• 分子量: 443.351
• InChiKey: MAAVMQOSSQQYOX-INIZCTEOSA-N

物化性质

• 熔点：
  134 °C
• 沸点：
  589.6±60.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  85.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-3,5-Dichloro-N-(2-(4-isopropyl-4,5-dihydrooxazol-2-yl)-6-methoxyphenyl)benzenesulfonamide 、 L-叔亮氨醇 在 zinc(II) chloride 、 ammonium hydroxide 作用下， 以 氯苯 、 水 为溶剂， 生成
  参考文献：
  名称：

  Toolbox Approach to the Search for Effective Ligands for Catalytic Asymmetric Cr-Mediated Coupling Reactions

  摘要：

  Chromium catalysts derived from chiral sulfonamides represented by A effect the couplings of aldehydes with vinyl, allyl, or alkyl halides. With three distinct sites for structural modification, A affords access to a structurally diverse pool of chiral sulfonamides. The Cr catalysts derived from these sulfonamides exhibit a broad range of catalyst-substrate matching profiles. A strategy is presented to search for a satisfactory chiral sulfonamide for a given substrate. In order to demonstrate the generality and effectiveness of this approach, five diverse C-C bond-forming cases have been selected from the halichondrin synthesis. For each of the cases, two ligands have been deliberately searched for, to induce the formation of (R)and (S)-alcohols, respectively, at the arbitrarily chosen efficiency level of ">= 80% yield with >= 20:1 stereoselectivity in the presence of <= 20 mol % of a Cr catalyst". For 9 out of the 10 cases studied, a satisfactory catalyst has been found within this pool of sulfonamides. Even for the remaining case, a Cr catalyst inducing stereoselectivity up to 8:1 has been identified.

  DOI：

  10.1021/ja905843e
• 作为产物：
  描述：

  3,5-二氯苯磺酰氯 、 在 吡啶 、 4-二甲氨基吡啶 、 甲醇 、 potassium carbonate 作用下， 生成 (R)-3,5-Dichloro-N-(2-(4-isopropyl-4,5-dihydrooxazol-2-yl)-6-methoxyphenyl)benzenesulfonamide
  参考文献：
  名称：

  Toolbox Approach to the Search for Effective Ligands for Catalytic Asymmetric Cr-Mediated Coupling Reactions

  摘要：

  Chromium catalysts derived from chiral sulfonamides represented by A effect the couplings of aldehydes with vinyl, allyl, or alkyl halides. With three distinct sites for structural modification, A affords access to a structurally diverse pool of chiral sulfonamides. The Cr catalysts derived from these sulfonamides exhibit a broad range of catalyst-substrate matching profiles. A strategy is presented to search for a satisfactory chiral sulfonamide for a given substrate. In order to demonstrate the generality and effectiveness of this approach, five diverse C-C bond-forming cases have been selected from the halichondrin synthesis. For each of the cases, two ligands have been deliberately searched for, to induce the formation of (R)and (S)-alcohols, respectively, at the arbitrarily chosen efficiency level of ">= 80% yield with >= 20:1 stereoselectivity in the presence of <= 20 mol % of a Cr catalyst". For 9 out of the 10 cases studied, a satisfactory catalyst has been found within this pool of sulfonamides. Even for the remaining case, a Cr catalyst inducing stereoselectivity up to 8:1 has been identified.

  DOI：

  10.1021/ja905843e
• 作为试剂：
  描述：

  6-((tert-butyldiphenylsilyl)oxy)hex-2-yn-1-ol 在 N-甲基咪唑 、 chromium dichloride 、 Sodium tetraborate decahydrate 、 Oxone 、 锰 、 9-borabicyclo[3.3.1]nonane dimer 、 四(三苯基膦)钯 、 二氯二茂锆 、 (R)-3,5-Dichloro-N-(2-(4-isopropyl-4,5-dihydrooxazol-2-yl)-6-methoxyphenyl)benzenesulfonamide 、 三正丁基氢锡 、 sodium acetate 、 四丁基硫酸氢铵 、 edetate disodium 、 1,8-双二甲氨基萘 、 potassium carbonate 、 sodium thiosulfate 、 间氯过氧苯甲酸 、 N-methylquinolinium hexafluorophosphate 、 1,2:4,5-双-O-(异亚丙基)-β-L-赤式-2,3-二酮-2,6-吡喃糖 、 lithium chloride 、 scandium tris(trifluoromethanesulfonate) 、 2-碘酰基苯甲酸 作用下， 以 四氢呋喃 、 1,1-二氯乙烷 、 二甲醇缩甲醛 、 二氯甲烷 、 水 、 二甲基亚砜 、 甲苯 、 乙腈 、 苯 为溶剂， 反应 83.5h， 生成 (5R,6R,8R)-6-((3S,7S)-3-hydroxy-7-((2R,5R)-2-methyl-5-(2-(triethylsilyloxy)propan-2-yl)tetrahydrofuran-2-yl)-4-methylene-7-(triethylsilyloxy)heptyl)-8-((S)-2-methyl-5-oxotetrahydrofuran-2-yl)-1,3,7-trioxaspiro[4.5]decan-2-one 、 (5R,6R,8R)-6-((3R,7S)-3-hydroxy-7-((2R,5R)-2-methyl-5-(2-(triethylsilyloxy)propan-2-yl)tetrahydrofuran-2-yl)-4-methylene-7-(triethylsilyloxy)heptyl)-8-((S)-2-methyl-5-oxotetrahydrofuran-2-yl)-1,3,7-trioxaspiro[4.5]decan-2-one
  参考文献：
  名称：

  蛋白磷酸酶2A抑制剂乳脱氢甲状腺甾醇的全合成

  摘要：

  级联环氧化物：角鲨烯衍生的聚醚乳脱氢甲状腺甾醇 ( 1 ) 是通过收敛序列制备的，该序列具有环氧化物开放级联以构建四氢呋喃和四氢吡喃亚基。其他特征包括立体发散的二烯双环氧化、三醇的单脱氧以及通过铃木和野崎-桧山-岸反应进行的复杂片段偶联。

  DOI：

  10.1002/anie.201007757

文献信息

• Chromium-mediated coupling and application to the synthesis of halichondrins
  申请人：President and Fellows of Harvard College

  公开号：US10344038B2

  公开（公告）日：2019-07-09

  The present invention provides unified synthesis of the CI-CI 9 building blocks of halichondrins and analogs thereof using selective coupling of poly-halogenated nucleophiles in chromium-mediated coupling reactions. The present invention also provides a practical and efficient synthesis of C20-C38 building blocks of halichondrins and analogs thereof. Also provided herein are general methods of selective activation and coupling of poly-halogenated analogs with an aldehyde. The provided coupling reactions are selective for halo-enone and halo-acetylenic ketal over vinyl halide and halide attached to a sp hydridized carbon. The provided efficient selective coupling reactions can allow easy access to the CI-CI 9 building blocks and C20-C38 building blocks of halichondrins and analogs thereof with limited or no purification or separation of the intermediates.

  本发明提供了在铬介导的偶联反应中利用多卤代亲核物的选择性偶联来统一合成卤代姜黄素及其类似物的 CI-CI 9 结构单元。本发明还提供了一种实用高效的卤代龙毒素及其类似物的 C20-C38 结构单元的合成方法。本发明还提供了选择性活化多卤代类似物并将其与醛偶联的一般方法。所提供的偶联反应对卤代烯酮和卤代乙炔缩酮具有选择性，而对乙烯基卤化物和连接到 sp 水化物碳上的卤化物则没有选择性。所提供的高效选择性偶联反应可以方便地获得卤代烯酮及其类似物的 CI-CI 9 结构单元和 C20-C38 结构单元，中间产物的纯化或分离程度有限或根本不需要。
• SYNTHESIS OF HALICHONDRINS
  申请人：President and Fellows of Harvard College

  公开号：EP3649135B1

  公开（公告）日：2022-12-28
• CHROMIUM-MEDIATED COUPLING AND APPLICATION TO THE SYNTHESIS OF HALICHONDRINS
  申请人：President and Fellows of Harvard College

  公开号：US20200031843A1

  公开（公告）日：2020-01-30

  The present invention provides unified synthesis of the C1-C19 building blocks of halichondrins and analogs thereof using selective coupling of poly-halogenated nucleophiles in chromium-mediated coupling reactions. The present invention also provides a practical and efficient synthesis of C20-C38 building blocks of halichondrins and analogs thereof. Also provided herein are general methods of selective activation and coupling of poly-halogenated analogs with an aldehyde. The provided coupling reactions are selective for halo-enone and halo-acetylenic ketal over vinyl halide and halide attached to a sp hybridized carbon. The provided efficient selective coupling reactions can allow easy access to the C1-C19 building blocks and C20-C38 building blocks of halichondrins and analogs thereof with limited or no purification or separation of the intermediates.
• [EN] CHROMIUM-MEDIATED COUPLING AND APPLICATION TO THE SYNTHESIS OF HALICHONDRINS<br/>[FR] COUPLAGE INDUIT PAR CHROME ET APPLICATION À LA SYNTHÈSE D'HALICHONDRINES
  申请人：HARVARD COLLEGE

  公开号：WO2016176560A1

  公开（公告）日：2016-11-03

  The present invention provides unified synthesis of the CI -CI 9 building blocks of halichondrins and analogs theoreof using selective coupling of poly-halogenated nucleophiles in chromium-mediated coupling reactions. The present invention also provides a practical and efficient synthesis of C20-C38 building blocks of halichondrins and analogs thereof. Also provided herein are general methods of selective activation and coupling of poly-halogenated analogs with an aldehyde. The provided coupling reactions are selective for halo-enone and halo-acetylenic ketal over vinyl halide and halide attached to a sp hydridized carbon. The provided efficient selective coupling reactions can allow easy access to the CI -CI 9 building blocks and C20-C38 building blocks of halichondrins and analogs thereof with limited or no purification or separation of the intermediates.
• [EN] SYNTHESIS OF HALICHONDRINS<br/>[FR] SYNTHÈSE D'HALICHONDRINES
  申请人：HARVARD COLLEGE

  公开号：WO2019010363A1

  公开（公告）日：2019-01-10

  The present invention provides methods for the synthesis of ketones involving a Ni/Zr-mediated coupling reaction. The Ni/Zr-mediated ketolization reactions can be used in the synthesis of halichondrins (e.g., halichondrin A, B, C; homohalichondrin A, B, C; norhalichondnn A, B, C), and analogs thereof. Therefore, the present invention also provides synthetic methods useful for the synthesis of halichondrins, and analogs thereof. Also provided herein are compounds (i.e., intermediates) useful in the synthesis of halichondrins, and analogs thereof. In particular, the present invention provides methods and compounds useful in the synthesis of compound of Formula (H3-A)