Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China.
Chem Asian J. 2010 Jun 1;5(6):1475-86. doi: 10.1002/asia.200900744.
The mechanism of a recently discovered intramolecular Heck-type coupling of oximes with aryl halides (Angew. Chem. Int. Ed. 2007, 46, 6325) was systematically studied by using density functional methods enhanced with a polarized continuum solvation model. The overall catalytic cycle of the reaction was found to consist of four steps: oxidative addition, migratory insertion, beta-H elimination, and catalyst regeneration, whereas an alternative base-promoted C-H activation pathway was determined to be less favorable. Migratory insertion was found to be the rate determining step in the catalytic cycle. The apparent activation barrier of migratory insertion of the (E)-oxime was +20.5 kcal mol(-1), whereas the barrier of (Z)-oxime was as high as +32.7 kcal mol(-1). However, (Z)-oxime could isomerize to form the more active (E)-oxime with the assistance of K(2)CO(3), so that both the (E)- and (Z)-oxime substrates could be transformed to the desired product. Our calculations also indicated that the Z product was predominant in the equilibrium of the isomerization of the imine double bond, which constituted the reason for the good Z-selectivity observed for the reaction. Furthermore, we examined the difference between the intermolecular Heck-type reactions of imines and of olefins. It was found that in the intermolecular Heck-type coupling of imines, the apparent activation barrier of migratory insertion was as high as +35 kcal mol(-1), which should be the main obstacle of the reaction. The analysis also revealed the main problem for the intermolecular Heck-type reactions of imines, which was that the breaking of a C=N pi bond was much more difficult than the breaking of a C=C pi bond. After systematic examination of a series of substituted imines, (Z)-N-amino imine and N-acetyl imine were found to have relatively low barriers of migratory insertion, so that they might be possible substrates for intermolecular Heck-type coupling.
用密度泛函理论结合极化连续溶剂模型系统研究了最近发现的肟与芳基卤化物的分子内 Heck 型偶联反应的机理（Angew. Chem. Int. Ed. 2007, 46, 6325）。反应的整个催化循环被发现由四个步骤组成：氧化加成、迁移插入、β-H 消除和催化剂再生，而确定了一种替代的碱促进的 C-H 活化途径不太有利。迁移插入被发现是催化循环中的速率决定步骤。（E）-肟的迁移插入的表观活化能垒为+20.5 kcal mol(-1)，而（Z）-肟的能垒高达+32.7 kcal mol(-1)。然而，（Z）-肟可以在 K(2)CO(3)的协助下异构化为更活跃的（E）-肟，从而使（E）-和（Z）-肟底物都可以转化为所需的产物。我们的计算还表明，在亚胺双键的异构化平衡中，Z 产物占优势，这构成了反应观察到的良好 Z-选择性的原因。此外，我们研究了亚胺和烯烃的分子间 Heck 型反应之间的差异。发现，在亚胺的分子间 Heck 型偶联中，迁移插入的表观活化能垒高达+35 kcal mol(-1)，这应该是反应的主要障碍。分析还揭示了亚胺的分子间 Heck 型反应的主要问题，即 C=N π 键的断裂比 C=C π 键的断裂困难得多。在对一系列取代亚胺进行系统考察后，发现（Z）-N-氨基亚胺和 N-乙酰亚胺具有相对较低的迁移插入能垒，因此它们可能是分子间 Heck 型偶联的可能底物。
