Zhang Xiaoming, Tobisch Sven, Hultzsch Kai C
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, 610 Taylor Road, Piscataway, NJ 08854-8087 (USA).
Chemistry. 2015 May 18;21(21):7841-57. doi: 10.1002/chem.201406468. Epub 2015 Apr 13.
The phenoxyamine magnesium complexes [{ONN}MgCH2 Ph] (4 a: {ONN}=2,4-tBu2 -6-(CH2 NMeCH2 CH2 NMe2 )C6 H2 O(-) ; 4 b: {ONN}=4-tBu-2-(CH2 NMeCH2 CH2 NMe2 )-6-(SiPh3 )C6 H2 O(-) ) have been prepared and investigated with respect to their catalytic activity in the intramolecular hydroamination of aminoalkenes. The sterically more shielded triphenylsilyl-substituted complex 4 b exhibits better thermal stability and higher catalytic activity. Kinetic investigations using complex 4 b in the cyclisation of 1-allylcyclohexyl)methylamine (5 b), respectively, 2,2-dimethylpent-4-en-1-amine (5 c), reveal a first-order rate dependence on substrate and catalyst concentration. A significant primary kinetic isotope effect of 3.9±0.2 in the cyclisation of 5 b suggests significant N-H bond disruption in the rate-determining transition state. The stoichiometric reaction of 4 b with 5 c revealed that at least two substrate molecules are required per magnesium centre to facilitate cyclisation. The reaction mechanism was further scrutinized computationally by examination of two rivalling mechanistic pathways. One scenario involves a coordinated amine molecule assisting in a concerted non-insertive N-C ring closure with concurrent amino proton transfer from the amine onto the olefin, effectively combining the insertion and protonolysis step to a single step. The alternative mechanistic scenario involves a reversible olefin insertion step followed by rate-determining protonolysis. DFT reveals that a proton-assisted concerted N-C/C-H bond-forming pathway is energetically prohibitive in comparison to the kinetically less demanding σ-insertive pathway (ΔΔG(≠) =5.6 kcal mol(-1) ). Thus, the σ-insertive pathway is likely traversed exclusively. The DFT predicted total barrier of 23.1 kcal mol(-1) (relative to the {ONN}Mg pyrrolide catalyst resting state) for magnesium-alkyl bond aminolysis matches the experimentally determined Eyring parameter (ΔG(≠) =24.1(±0.6) kcal mol(-1) (298 K)) gratifyingly well.
已制备出苯氧基胺镁配合物[{ONN}MgCH₂Ph]（4 a：{ONN}=2,4-二叔丁基-6-(CH₂NMeCH₂CH₂NMe₂)C₆H₂O⁻；4 b：{ONN}=4-叔丁基-2-(CH₂NMeCH₂CH₂NMe₂)-6-(三苯基硅基)C₆H₂O⁻），并研究了它们在氨基烯烃分子内氢胺化反应中的催化活性。空间位阻更大的三苯基硅基取代配合物4 b表现出更好的热稳定性和更高的催化活性。分别使用配合物4 b对1-烯丙基环己基甲基胺（5 b）和2,2-二甲基戊-4-烯-1-胺（5 c）进行环化反应的动力学研究表明，反应速率对底物和催化剂浓度呈一级依赖关系。在5 b环化反应中观察到显著的一级动力学同位素效应，kH/kD = 3.9±0.2，这表明在速率决定过渡态中N-H键发生了显著断裂。4 b与5 c的化学计量反应表明，每个镁中心至少需要两个底物分子才能促进环化反应。通过研究两条相互竞争的反应机理途径，对反应机理进行了进一步的计算研究。一种情况是，一个配位的胺分子协助进行协同的非插入式N-C环闭合，同时胺上的氨基质子转移到烯烃上，有效地将插入步骤和质子解步骤合并为一个步骤。另一种反应机理情况是，先进行可逆的烯烃插入步骤，然后是速率决定的质子解步骤。密度泛函理论（DFT）表明，与动力学要求较低的σ-插入途径相比，质子辅助的协同N-C/C-H键形成途径在能量上是不利的（ΔΔG(≠) =5.6 kcal mol⁻¹）。因此，可能仅通过σ-插入途径进行反应。DFT预测的镁-烷基键氨解反应的总势垒为23.1 kcal mol⁻¹（相对于{ONN}Mg吡咯化物催化剂的基态），与实验测定的艾林参数（ΔG(≠) =24.1(±0.6) kcal mol⁻¹（298 K））非常吻合。
