2,2,2-trichloro-N-((1R,3S,5R)-6,6-dimethyl-2-methylenebicyclo[3.1.1]heptan-3-yl)acetamide | 199801-80-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 2,2,2-trichloro-N-((1R,3S,5R)-6,6-dimethyl-2-methylenebicyclo[3.1.1]heptan-3-yl)acetamide
• 英文别名: 2,2,2-trichloro-N-[(1R,3S,5R)-6,6-dimethyl-2-methylidene-3-bicyclo[3.1.1]heptanyl]acetamide
• CAS: 199801-80-4
• 化学式: C₁₂H₁₆Cl₃NO
• 分子量: 296.624
• InChiKey: YJPWMPVCJHDKHD-VGMNWLOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2,2,2-trichloro-N-((1R,3S,5R)-6,6-dimethyl-2-methylenebicyclo[3.1.1]heptan-3-yl)acetamide 在 盐酸 、 四氧化锇 、 N-甲基吗啉氧化物 、 potassium hydroxide 作用下， 以 乙醚 、 水 、 丙酮 、 叔丁醇 为溶剂， 反应 74.0h， 生成 (1R,2R,3S,5R)-3-isopropylamino-2-hydroxymethyl-6,6-dimethylbicyclo[3.1.1]heptan-2-ol
  参考文献：
  名称：

  Stereoselective synthesis of pinane-type tridentate aminodiols and their application in the enantioselective addition of diethylzinc to benzaldehyde

  摘要：

  A library of pinane-based aminodiols were prepared from commercially available (1R)-(-)-myrtenol (-)-1. Compound (-)-1 was transformed into ally! trichloroacetamide (+)-2 via the acetimidate, followed by the Overman rearrangement. In order obtain the aminodiol structure, (+)-2 was subjected to stereoselective dihydroxylation with OsO4, resulting in dihydroxy trichloroacetamide (+)-3. The trichloroacetyl group was removed from (+)-3 with aqueous HCl and the (1R,2R,3S,5R)-3-amino-2-hydroxymethyl-6,6-dimethylbicyclo[3.1.1]heptan-2-ol hydrochloride (-)-4 obtained was transformed to primary, secondary and tertiary aminodiols by reductive amination, N-alkylation of aminodiol (+)-9 and debenzylation of N-benzyl aminodiol (+)-10, respectively. In the reactions of (+)-9 and (+)-14 with formaldehyde, highly regioselective ring closure was observed. In contrast with earlier results, the aminodiols gave pinane-fused oxazolidines (+)-11 and (-)-15. The aminodiols and their oxazolidine derivatives 5-15 were applied as chiral catalysts in the enantioselective addition of diethylzinc to benzaldehyde. The best enantioselectivity was observed in the case of the N-benzyl-substituted derivative (+)-9. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2012.01.020
• 作为产物：
  描述：

  (-)-桃金娘烯醇 在 potassium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 、 二氯甲烷 为溶剂， 反应 29.0h， 生成 2,2,2-trichloro-N-((1R,3S,5R)-6,6-dimethyl-2-methylenebicyclo[3.1.1]heptan-3-yl)acetamide
  参考文献：
  名称：

  pin烷型1,3-二氨基醇的立体选择性合成与转化

  摘要：

  从市售的（1 R）-（-）-myrtenol开发了基于pin烷的1,3-二氨基醇和5-氨基甲基恶唑烷-2-酮的文库，将其通过Overmann重排然后立体选择性转化为N-三氯乙酰基保护的烯丙胺环氧化与米CPBA导致键intermedier环氧树脂-胺。为了获得二氨基醇部分，进行环氧乙烷环的氨基解和叠氮解。环氧乙烷环的裂解是区域选择性进行的，得到N-三氯乙酰基保护的1，3-二氨基醇和恶唑烷-2-酮，它们也是通过热环化获得的。由于N二氨基醇的脱保护在各种条件下均不成功，保护基被改变并且Boc-保护的类似物被合成。在这种情况下，成功去除Boc保护基产生了计划中的二氨基醇。一个意想不到的极端δ我α -9值（0.11 ppm的）测量为dibenzylaminomethyl取代恶唑烷-2-酮，和其立体物通过的DFT几何优化手段精制。将获得的潜在催化剂用于低至中等对映选择性（最高74％ee）的苯甲醛和二乙基锌的测试反应中。

  DOI：

  10.1016/j.tet.2017.03.050

文献信息

• One-Pot Transformation of Trichloroacetamide into Readily Deprotectable Carbamates
  作者：Toshio Nishikawa、Daisuke Urabe、Miho Tomita、Takashi Tsujimoto、Tomoko Iwabuchi、Minoru Isobe

  DOI：10.1021/ol061123c

  日期：2006.7.1

  A trichloroacetamide group was converted to an isocyanate, which was in situ captured by a variety of alcohols in the presence of CuCl and n-BuN4Cl to afford the corresponding carbamates. The scope and limitation of this transformation are also described.
• Improved Conditions for Facile Overman Rearrangement¹
  作者：Toshio Nishikawa、Masanori Asai、Norio Ohyabu、Minoru Isobe

  DOI：10.1021/jo9713924

  日期：1998.1.1
• Stereoselective synthesis of pinane-type tridentate aminodiols and their application in the enantioselective addition of diethylzinc to benzaldehyde
  作者：Kinga Csillag、Lukács Németh、Tamás A. Martinek、Zsolt Szakonyi、Ferenc Fülöp

  DOI：10.1016/j.tetasy.2012.01.020

  日期：2012.1

  A library of pinane-based aminodiols were prepared from commercially available (1R)-(-)-myrtenol (-)-1. Compound (-)-1 was transformed into ally! trichloroacetamide (+)-2 via the acetimidate, followed by the Overman rearrangement. In order obtain the aminodiol structure, (+)-2 was subjected to stereoselective dihydroxylation with OsO4, resulting in dihydroxy trichloroacetamide (+)-3. The trichloroacetyl group was removed from (+)-3 with aqueous HCl and the (1R,2R,3S,5R)-3-amino-2-hydroxymethyl-6,6-dimethylbicyclo[3.1.1]heptan-2-ol hydrochloride (-)-4 obtained was transformed to primary, secondary and tertiary aminodiols by reductive amination, N-alkylation of aminodiol (+)-9 and debenzylation of N-benzyl aminodiol (+)-10, respectively. In the reactions of (+)-9 and (+)-14 with formaldehyde, highly regioselective ring closure was observed. In contrast with earlier results, the aminodiols gave pinane-fused oxazolidines (+)-11 and (-)-15. The aminodiols and their oxazolidine derivatives 5-15 were applied as chiral catalysts in the enantioselective addition of diethylzinc to benzaldehyde. The best enantioselectivity was observed in the case of the N-benzyl-substituted derivative (+)-9. (C) 2012 Elsevier Ltd. All rights reserved.
• Stereoselective synthesis and transformations of pinane-based 1,3-diaminoalcohols
  作者：Tímea Gonda、Attila Balázs、Gábor Tóth、Ferenc Fülöp、Zsolt Szakonyi

  DOI：10.1016/j.tet.2017.03.050

  日期：2017.5

  Overmann rearrangement followed by stereoselective epoxidation with mCPBA resulting in key intermedier epoxy-amine. In order to obtain the diaminoalcohol moiety, aminolysis and azidolysis of the oxirane ring was performed. The cleavage of the oxirane ring proceeded regioselectively, affording N-trichloroacetyl protected 1,3-diaminoalcohols and oxazolidin-2-ones, which were obtained also via a thermal cyclisation

  从市售的（1 R）-（-）-myrtenol开发了基于pin烷的1,3-二氨基醇和5-氨基甲基恶唑烷-2-酮的文库，将其通过Overmann重排然后立体选择性转化为N-三氯乙酰基保护的烯丙胺环氧化与米CPBA导致键intermedier环氧树脂-胺。为了获得二氨基醇部分，进行环氧乙烷环的氨基解和叠氮解。环氧乙烷环的裂解是区域选择性进行的，得到N-三氯乙酰基保护的1，3-二氨基醇和恶唑烷-2-酮，它们也是通过热环化获得的。由于N二氨基醇的脱保护在各种条件下均不成功，保护基被改变并且Boc-保护的类似物被合成。在这种情况下，成功去除Boc保护基产生了计划中的二氨基醇。一个意想不到的极端δ我α -9值（0.11 ppm的）测量为dibenzylaminomethyl取代恶唑烷-2-酮，和其立体物通过的DFT几何优化手段精制。将获得的潜在催化剂用于低至中等对映选择性（最高74％ee）的苯甲醛和二乙基锌的测试反应中。