1-(cyclohexylmethyl)-2-methyl-4,4-diphenylpyrrolidine | 1009105-75-2

• 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: 1-(cyclohexylmethyl)-2-methyl-4,4-diphenylpyrrolidine
• CAS: 1009105-75-2
• 化学式: C₂₄H₃₁N
• 分子量: 333.517
• InChiKey: BJGNMVFKRWOVFE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  N-(cyclohexylmethyl)-2,2-diphenylpent-4-en-1-amine 在 (κ2-{2-i-Pr2PC6H4}O)Ir(COD) 作用下， 以 1,4-二氧六环 为溶剂， 反应 24.0h， 以89%的产率得到1-(cyclohexylmethyl)-2-methyl-4,4-diphenylpyrrolidine
  参考文献：
  名称：

  Intramolecular hydroamination of unactivated alkenes with secondary alkylamines catalyzed by iridium phosphino–phenolate complexes

  摘要：

  研究表明，膦酚络合物 (κ2-{2-i-Pr2PC6H4}O)Ir(COD)（COD = η4-1,5-环辛二烯；1）是一种有效的前催化剂，可用于未活化的烯烃与下垂的仲烷基胺发生分子内氢化反应，从而以较高的分离产率提供吡咯烷或哌啶杂环。在监测此类选定试验反应的进展时，观察到一个显著的诱导期（约 3 小时）；在催化相关条件下进行的变温 1H 和 31P NMR 研究（25-100 °C）没有发现新的含金属物种。为了开发 1 的对映体纯变体，我们开发了手性 (κ2-P,O)Ir(COD) 复合物 (7) 的合成路线，该复合物具有 1-芳基-2,5-二烷基磷脂结构，源自 (2S,5S)-2,5-己二醇环硫酸盐。利用单晶 X 射线衍射技术确认了 7 的结构。虽然 7 未能在未活化的烯烃与悬垂仲烷基胺的分子内氢化反应中提供对映选择性，但发现 7 的活性与 1 相当。

  DOI：

  10.1139/v09-181

文献信息

• [Ir(COD)Cl]₂ as a Catalyst Precursor for the Intramolecular Hydroamination of Unactivated Alkenes with Primary Amines and Secondary Alkyl- or Arylamines: A Combined Catalytic, Mechanistic, and Computational Investigation
  作者：Kevin D. Hesp、Sven Tobisch、Mark Stradiotto

  DOI：10.1021/ja908316n

  日期：2010.1.13

  scrutinized computationally. An energetically demanding oxidative addition of the amine N-H bond to the Ir(I) center precludes the latter mechanism and instead activation of the olefin C=C bond prevails, with [Ir(COD)Cl(substrate)] M1 representing the catalytically competent compound. Notably, such an olefin activation mechanism had not previously been documented for Ir-catalyzed alkene hydroamination. The

  报道了 [Ir(COD)Cl](2) 作为预催化剂的成功应用，用于在相对低的催化剂负载下将伯和仲烷基胺或芳基胺分子内加成到未活化的烯烃上（25 个例子），以及一个全面的反应机理的实验和计算研究。检查 N-苄基-2,2-二苯基戊-4-en-1-胺 (1a) 环化成相应吡咯烷 (2a) 的催化剂优化研究表明，对于在 110 摄氏度进行的反应，既不添加盐 (N (n)Bu(4)Cl、LiOTf、AgBF(4) 或 LiB(C(6)F(5))(4) x 2.5 OEt(2)) 或膦共配体都用于提高 [Ir (COD)Cl](2)。在这方面，使用 [Ir(COD)Cl](2)/L2（L2 = 2-（二叔丁基膦基）联苯）催化剂混合物的 1a 的分子内加氢胺化速率在 65 摄氏度时表现出对 L2 的逆序依赖性，并且在 110 摄氏度时对 L2 的零级速率依赖性。然而，需要使用 5 mol% HNEt(3)Cl
• Inter- and Intramolecular Hydroamination of Unactivated Alkenes Catalysed by a Combination of Copper and Silver Salts: The Unveiling of a Brønstedt Acid Catalysis
  作者：Christophe Michon、Florian Medina、Frédéric Capet、Pascal Roussel、Francine Agbossou-Niedercorn

  DOI：10.1002/adsc.201000536

  日期：2010.12.17

  The combined use of a copper halide, a silver salt and a phosphane ligand was applied for the catalysis of inter- and intramolecular hydroamination of alkenes. The reactions of unactivated olefins with nitrogen substrates were investigated. Mechanistic investigations demonstrated that the catalytic system generated a Brønsted acid which appeared to be the prominent catalytic species.

  卤化铜，银盐和膦配体的组合使用被用于催化烯烃的分子间和分子内加氢胺化。研究了未活化烯烃与氮底物的反应。机理研究表明，该催化体系产生了布朗斯台德酸，该酸似乎是主要的催化物种。
• Mild, Rhodium-Catalyzed Intramolecular Hydroamination of Unactivated Terminal and Internal Alkenes with Primary and Secondary Amines
  作者：Zhijian Liu、John F. Hartwig

  DOI：10.1021/ja710126x

  日期：2008.2.6

  We report a series of mild, rhodium-catalyzed hydroaminations of unactivated olefins with primary and secondary alkylamines to form the corresponding five- and six-membered products in excellent yields. The reactions form exclusively the product from hydroamination without competitive oxidative amination or olefin isomerization with catalysts generated from a biaryl dialkyl phosphine and an analogue

  我们报道了一系列温和的铑催化未活化烯烃与伯烷基胺和仲烷基胺的氢胺化反应，以优异的收率形成相应的五元和六元产物。该反应仅通过加氢胺化形成产物，而无需使用由联芳基二烷基膦和Xantphos类似物产生的催化剂进行竞争性氧化胺化或烯烃异构化。加氢胺化过程可耐受多种官能团，包括羟基、卤素、氰基和烷氧羰基。
• Hydroamination of Alkenes
  申请人：Takemiya Akihiro

  公开号：US20090156824A1

  公开（公告）日：2009-06-18

  A method includes reacting an amino group, a composition including rhodium and an organic ligand, and a substrate having structural formula (I) in a reaction mixture. R 1 is an organic group including a sp 3 carbon atom bonded to C A . R 2 is selected from the group consisting of hydrogen, methyl, and an organic group including a sp 3 carbon atom bonded to C A . R 3 and R 4 independently are selected from the group consisting of hydrogen, methyl, and an organic group including a sp 3 carbon atom bonded to C B . The method further includes forming a hydroaminated product in the reaction mixture.

  一种方法包括在反应混合物中反应氨基基团、包括铑和有机配体的组合物以及具有结构式（I）的底物。其中，R1是包括与CA键合的sp3碳原子的有机基团。R2从氢、甲基和包括与CA键合的sp3碳原子的有机基团的组中选择。R3和R4独立地从氢、甲基和包括与CB键合的sp3碳原子的有机基团的组中选择。该方法进一步包括在反应混合物中形成一个羟胺化产物。
• Intramolecular hydroamination of unactivated alkenes with secondary alkylamines catalyzed by iridium phosphino–phenolate complexes
  作者：Kevin D. Hesp、Robert McDonald、Mark Stradiotto

  DOI：10.1139/v09-181

  日期：2010.8

  The phosphino–phenolate complex (κ²-2-i-Pr₂PC₆H₄}O)Ir(COD) (COD = η⁴-1,5-cyclooctadiene; 1) is shown to be an effective precatalyst for the intramolecular hydroamination of unactivated alkenes with pendant secondary alkylamines, providing either pyrrolidine or piperidine heterocycles in high isolated yields. While monitoring the progress of a selected test reaction of this type, a significant induction period (~3 h) was observed; variable-temperature ¹H and ³¹P NMR studies (25–100 °C) under catalytically relevant conditions revealed no new metal-containing species. In an effort to develop an enantiopure variant of 1, a synthetic route to the chiral (κ²-P,O)Ir(COD) complex (7), which features a 1-aryl-2,5-dialkylphospholane structure derived from (2S,5S)-2,5-hexanediol cyclic sulfate, was developed. The structure of 7 was confirmed by use of single-crystal X-ray diffraction techniques. While 7 failed to provide enantioselectivity in the intramolecular hydroamination of unactivated alkenes with pendant secondary alkylamines, the activity of 7 was found to be comparable to that of 1.

  研究表明，膦酚络合物 (κ2-2-i-Pr2PC6H4}O)Ir(COD)（COD = η4-1,5-环辛二烯；1）是一种有效的前催化剂，可用于未活化的烯烃与下垂的仲烷基胺发生分子内氢化反应，从而以较高的分离产率提供吡咯烷或哌啶杂环。在监测此类选定试验反应的进展时，观察到一个显著的诱导期（约 3 小时）；在催化相关条件下进行的变温 1H 和 31P NMR 研究（25-100 °C）没有发现新的含金属物种。为了开发 1 的对映体纯变体，我们开发了手性 (κ2-P,O)Ir(COD) 复合物 (7) 的合成路线，该复合物具有 1-芳基-2,5-二烷基磷脂结构，源自 (2S,5S)-2,5-己二醇环硫酸盐。利用单晶 X 射线衍射技术确认了 7 的结构。虽然 7 未能在未活化的烯烃与悬垂仲烷基胺的分子内氢化反应中提供对映选择性，但发现 7 的活性与 1 相当。