The Grignard Reaction - Unraveling a Chemical Puzzle
The Grignard Reaction - Unraveling a Chemical Puzzle
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DOI：
10.1021/jacs.9b11829
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发表时间：
2020-02-12
影响因子：
15
通讯作者：
Cascella, Michele
中科院分区：
文献类型：
--
作者：
Peltzer, Raphael Mathias;Gauss, Juergen;Cascella, Michele
自发现100多年以来，Grignard反应的机制仍然没有得到解决。歧义产生的同时存在的多个有机镁物种和竞争机制，涉及亲核加成或自由基中间体的形成。为了阐明这一主题，量子化学计算和从头算分子动力学模拟研究的CH 3 MgCl在四氢呋喃与乙醛和芴酮为原型试剂的反应。所有有机镁物种共存于溶液中，由于Schlenk平衡被发现是主管试剂的亲核途径。所有这些化合物显示的活化能的范围相对较小。最具反应性的物种是双核镁络合物，其中底物和亲核试剂最初与不同的镁中心和单核二甲基镁结合。自由基反应需要Mg-CH 3键的均裂，除非具有低位pi*（CO）轨道的底物与Mg中心配位，否则不能发生。这就解释了为什么只有在还原电位低的底物存在下才能检测到自由基机制。这一特点，反过来，并不一定有利于亲核加成，如所示的与芴酮的反应。溶剂需要被认为是亲核和自由基反应的反应物，其动力学是必不可少的代表能量分布。几种物质在快速平衡中的相似反应性意味着反应不是通过单一过程发生的，而是通过平行反应的集合发生的。
More than 100 years since its discovery, the mechanism of the Grignard reaction remains unresolved. Ambiguities arise from the concomitant presence of multiple organomagnesium species and the competing mechanisms involving either nucleophilic addition or the formation of radical intermediates. To shed light on this topic, quantum-chemical calculations and ab initio molecular dynamics simulations are used to study the reaction of CH3MgCl in tetrahydrofuran with acetaldehyde and fluorenone as prototypical reagents. All organo-magnesium species coexisting in solution due to the Schlenk equilibrium are found to be competent reagents for the nucleophilic pathway. The range of activation energies displayed by all of these compounds is relatively small. The most reactive species are a dinuclear Mg complex in which the substrate and the nucleophile initially bind to different Mg centers and the mononuclear dimethyl magnesium. The radical reaction, which requires the homolytic cleavage of the Mg-CH3 bond, cannot occur unless a substrate with a low-lying pi*(CO) orbital coordinates the Mg center. This rationalizes why a radical mechanism is detected only in the presence of substrates with a low reduction potential. This feature, in turn, does not necessarily favor the nucleophilic addition, as shown for the reaction with fluorenone. The solvent needs to be considered as a reactant for both the nucleophilic and the radical reactions, and its dynamics is essential for representing the energy profile. The similar reactivity of several species in fast equilibrium implies that the reaction does not occur via a single process but by an ensemble of parallel reactions.