College of Chemistry and Chemical Engineering, Graduate University of Chinese Academy of Science, Beijing 100049, PR China.
Dalton Trans. 2012 Aug 14;41(30):9091-100. doi: 10.1039/c2dt30329a. Epub 2012 May 14.
Frustrated Lewis pairs (FLPs) has been applied to catalytic metal-free hydrogenation. Can the FLP reactivity be used for catalytic hydroamination? Using density functional theory (DFT) calculations, we have explored whether the molecules cat1-cat3, which were previously designed by integrating the dearomatization-aromatization effect and the FLP reactivity, can catalyze the intramolecular hydroaminations of non-activated aminoalkenes to afford nitrogen heterocycles. The study shows that the γ-aminoalkene (am1) hydroamination catalyzed by cat1 proceeds via two steps (aminoalkene N-H bond activation and C-N bond formation) with experimentally accessible energetics, giving the five-membered nitrogen heterocycle product 1,1-dimethylpyrrolidine. The N-H bond activation is reversible. The C-N bond formation step undergoes a concerted mechanism and complies with the Markovnikov addition rule. Possible side reactions which may cause catalyst deactivation were confirmed to be energetically unfavorable. The molecules cat2 and cat3 are less effective than cat1 in catalyzing the am1 hydroamination, but the barriers are not too high. By following the most favorable pathway of the cat1-mediated am1 hydroamination, we further extended the substrate (am1) to other aminoalkenes, including the methyl and phenyl β-substituted am1 (i.e. am2 and am3, respectively), the benzyl-protected primary aminoalkene (am4), and the δ-aminoalkene (am5). The hydroaminations of am2 and am3 have energetics comparable with am1 hydroamination, the am5 hydroamination is energetically less favorable, and the am4 hydroamination is least favorable but could be realizable by elevating the temperature and pressure. We call experimental efforts to synthesize cat1-cat3 or similar new molecules on the basis of the design strategy.
frustrated Lewis 对（FLPs）已被应用于催化无金属氢化。FLP 的反应性是否可用于催化氢胺化？我们使用密度泛函理论（DFT）计算来探索先前通过整合去芳构化-芳构化效应和 FLP 反应性设计的分子 cat1-cat3 是否可以催化非活化的氨基烯烃的分子内氢胺化反应，以获得氮杂环。研究表明，cat1 催化的 γ-氨基烯烃（am1）氢胺化反应通过两个步骤（氨基烯烃 N-H 键活化和 C-N 键形成）进行，具有可实验获得的能量学，得到五元氮杂环产物 1,1-二甲基吡咯烷。N-H 键活化是可逆的。C-N 键形成步骤经历协同机制并符合马氏加成规则。可能导致催化剂失活的可能副反应被证实能量不利。分子 cat2 和 cat3 催化 am1 氢胺化的效果不如 cat1，但障碍并不太高。通过遵循 cat1 介导的 am1 氢胺化的最有利途径，我们进一步扩展了底物（am1）至其他氨基烯烃，包括甲基和苯基β取代的 am1（即 am2 和 am3）、苄基保护的伯氨基烯烃（am4）和δ-氨基烯烃（am5）。am2 和 am3 的氢胺化反应具有与 am1 氢胺化反应可比的能量学，am5 的氢胺化反应能量学不利，am4 的氢胺化反应最不利，但可以通过升高温度和压力来实现。我们呼吁根据设计策略合成 cat1-cat3 或类似新分子的实验努力。
