tert-butyl (1R,5S)-2-oxo-8-azabicyclo[3.2.1]octane-8-carboxylate

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: tert-butyl (1R,5S)-2-oxo-8-azabicyclo[3.2.1]octane-8-carboxylate
• 化学式: C₁₂H₁₉NO₃
• 分子量: 225.288
• InChiKey: SJGXXUBCKFNNGB-DTWKUNHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl (1R,5S)-2-oxo-8-azabicyclo[3.2.1]octane-8-carboxylate 在 4-二甲氨基吡啶 、 sodium hydroxide 、 双氧水 、 sodium hydride 、 sodium cyanoborohydride 、 sodium carbonate 、 三氟乙酸 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 乙酸酐 、 溶剂黄146 、 甲苯 、 乙腈 为溶剂， 反应 88.67h， 生成 古卡因
  参考文献：
  名称：

  Enantiospecific Synthesis of Natural (−)-Cocaine and Unnatural (+)-Cocaine from d- and l-Glutamic Acid

  摘要：

  Natural (-)-cocaine and unnatural (+)-cocaine have been synthesized enantiospecifically from D- and L-glutamic acid, respectively. The axial-equatorial substitutents were introduced by a stereo- and regiospecific dipolar cycloaddition to the corresponding (LR,5S)- and (1S,5R)-N-BOC-nortropenes with (ethoxycarbonyl)formonitrile N-oxide. A sequence of subsequent stereochemically controlled transformations converted the fused isoxazoline to the requisite P-hydroxy ester. Synthesis of the key intermediate N-BOC-nortropenes involved construction of the 8-azabicyclo[3.2.1]octane framework by Dieckmann condensation of cis-5-substituted D-and L-proline esters. For comparison, (1R,SS)-N-BOC-nortropene also was derived by degradation from natural cocaine. The cis-5-substituted D-and L-proline esters were obtained by sulfide contraction and subsequent catalytic hydrogenation to induce stereospecifically the C-5 stereochemistry from D-and L-thiopyroglutamate, which in turn were prepared from D-and L-glutamic acids, respectively.

  DOI：

  10.1021/jo980153t
• 作为产物：
  描述：

  环庚酮 在 N-溴代丁二酰亚胺(NBS) 、 [Fe^III(5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrinato)(1,3-dimethylimidazol-2-ylidene)₂]I 、 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 36.5h， 生成 tert-butyl (1R,5S)-2-oxo-8-azabicyclo[3.2.1]octane-8-carboxylate
  参考文献：
  名称：

  N-杂环碳烯铁（III）卟啉催化的烷基叠氮化物的分子内C（sp3）-H胺化

  摘要：

  金属催化的叠氮化物分子内CH胺化反应是脂环族胺的一种吸引人的方法。扩大底物范围，增强区域选择性以及将该方法应用于天然产物合成方面仍然存在挑战。在本文中，我们报道了带有轴向N-杂环卡宾配体的铁（III）卟啉，其催化分子内C（sp 3）–在微波辅助和热条件下进行多种烷基叠氮化物的H胺化反应，从而选择性地胺化叔，苄基，烯丙基，仲和伯CH键，产率高达95％。将17种底物中的14种在C4选择性环化，得到吡咯烷。可以通过改变C5-H键的反应性来调节C4或C5的区域选择性。机理研究揭示了胺化反应的协调或快速重新结合机制。该反应已被用于合成托烷，尼古丁，顺式八氢吲哚和Leelamine衍生物。

  DOI：

  10.1002/anie.201806059

文献信息

• An Effective [Fe^III(TF₄DMAP)Cl] Catalyst for C–H Bond Amination with Aryl and Alkyl Azides
  作者：Yi-Dan Du、Zhen-Jiang Xu、Cong-Ying Zhou、Chi-Ming Che

  DOI：10.1021/acs.orglett.8b03765

  日期：2019.2.15

  [FeIII(TF4DMAP)Cl] can efficiently catalyze intermolecular sp3 C–H amination using aryl azides and intramolecular sp3 C–H amination of alkyl azides in moderate-to-high product yields. At catalyst loading down to 1 mol %, the reactions display high chemo- and regioselectivity with broad substrate scope and are effective for late-stage functionalization of complex natural/bioactive molecules.

  的[Fe III（TF 4 DMAP）CL]可以有效地催化分子间的SP 3 C-H使用芳基叠氮化和分子内藻胺化3烷基叠氮化物的C-H的胺化在中度到高的产物收率。在低至1 mol％的催化剂负载量下，反应显示出高的化学选择性和区域选择性以及广泛的底物范围，并且对于复杂的天然/生物活性分子的后期功能化有效。
• Iron porphyrin catalysed light driven C–H bond amination and alkene aziridination with organic azides
  作者：Yi-Dan Du、Cong-Ying Zhou、Wai-Pong To、Hai-Xu Wang、Chi-Ming Che

  DOI：10.1039/d0sc00784f

  日期：——

  strategy for the design of C–N bond formation reactions under mild reaction conditions, the challenge being lack of selectivity as a free nitrene reactive intermediate is usually involved. Herein is described an iron(III) porphyrin catalysed sp3 C–H amination and alkene aziridination with selectivity by using organic azides as the nitrogen source under blue LED light (469 nm) irradiation. The photochemical

  在温和的反应条件下，可见光驱动的有机叠氮化物的氮烯转移和插入反应是设计C–N键形成反应的一种有吸引力的策略，因为通常涉及游离的腈反应性中间体，因此缺乏选择性的挑战。本文描述了铁（III）卟啉催化的sp 3通过使用有机叠氮化物作为氮源，在蓝色LED光（469 nm）照射下，进行C–H胺化和烯烃的叠氮化。光化学反应显示化学选择性和区域选择性，并且对于复杂的天然和生物活性化合物的后期功能化有效。机理研究表明，卟啉铁既起光敏剂的作用，又起催化剂的作用，产生了反应性的铁-氮化物中间体，随后形成C-N键。
• Carbonyl 1,2-transposition through triflate-mediated α-amination
  作者：Zhao Wu、Xiaolong Xu、Jianchun Wang、Guangbin Dong

  DOI：10.1126/science.abl7854

  日期：2021.11.5

  Chemists devote tremendous effort to the precise placement of oxygens in molecular frameworks. Wu et al . report a convenient method to shift the oxygen in a carbonyl group to an adjacent carbon center. After activation of the oxygen to an alkenyl triflate, cooperative catalysis by palladium and norbornene adds nitrogen to the neighboring carbon while displacing the triflate with hydride. Hydrolysis then produces the desired shifted ketone. The protocol is well suited to late-stage variation of complex molecules during drug optimization. —JSY

  标题：酮转移的谨慎编排 化学家们致力于在分子框架中精确放置氧原子。吴等人报告了一种方便的方法，将羰基中的氧转移到相邻的碳中心。在将氧活化为烯基三氟乙酸酯后，钯和环辛烯的协同催化作用在邻近碳上加入氮，同时用氢化物取代三氟乙酸酯。然后水解产生所需的转移酮。该协议非常适合在药物优化期间对复杂分子进行后期变异。 —JSY
• N-Heterocyclic Carbene Iron(III) Porphyrin-Catalyzed Intramolecular C(sp³ )-H Amination of Alkyl Azides
  作者：Ka-Pan Shing、Yungen Liu、Bei Cao、Xiao-Yong Chang、Tingjie You、Chi-Ming Che

  DOI：10.1002/anie.201806059

  日期：2018.9.10

  selective amination of tertiary, benzylic, allylic, secondary, and primary C−H bonds with up to 95 % yield. 14 out of 17 substrates were cyclized selectively at C4 to give pyrrolidines. The regioselectivity at C4 or C5 could be tuned by modifying the reactivity of the C5–H bond. Mechanistic studies revealed a concerted or a fast re‐bound mechanism for the amination reaction. The reaction has been applied

  金属催化的叠氮化物分子内CH胺化反应是脂环族胺的一种吸引人的方法。扩大底物范围，增强区域选择性以及将该方法应用于天然产物合成方面仍然存在挑战。在本文中，我们报道了带有轴向N-杂环卡宾配体的铁（III）卟啉，其催化分子内C（sp 3）–在微波辅助和热条件下进行多种烷基叠氮化物的H胺化反应，从而选择性地胺化叔，苄基，烯丙基，仲和伯CH键，产率高达95％。将17种底物中的14种在C4选择性环化，得到吡咯烷。可以通过改变C5-H键的反应性来调节C4或C5的区域选择性。机理研究揭示了胺化反应的协调或快速重新结合机制。该反应已被用于合成托烷，尼古丁，顺式八氢吲哚和Leelamine衍生物。
• Enantiospecific Synthesis of Natural (−)-Cocaine and Unnatural (+)-Cocaine from <scp>d</scp>- and <scp>l</scp>-Glutamic Acid
  作者：Ronghui Lin、Josep Castells、Henry Rapoport

  DOI：10.1021/jo980153t

  日期：1998.6.1

  Natural (-)-cocaine and unnatural (+)-cocaine have been synthesized enantiospecifically from D- and L-glutamic acid, respectively. The axial-equatorial substitutents were introduced by a stereo- and regiospecific dipolar cycloaddition to the corresponding (LR,5S)- and (1S,5R)-N-BOC-nortropenes with (ethoxycarbonyl)formonitrile N-oxide. A sequence of subsequent stereochemically controlled transformations converted the fused isoxazoline to the requisite P-hydroxy ester. Synthesis of the key intermediate N-BOC-nortropenes involved construction of the 8-azabicyclo[3.2.1]octane framework by Dieckmann condensation of cis-5-substituted D-and L-proline esters. For comparison, (1R,SS)-N-BOC-nortropene also was derived by degradation from natural cocaine. The cis-5-substituted D-and L-proline esters were obtained by sulfide contraction and subsequent catalytic hydrogenation to induce stereospecifically the C-5 stereochemistry from D-and L-thiopyroglutamate, which in turn were prepared from D-and L-glutamic acids, respectively.