Quantum Chemical Investigation of Dimerization in the Schlenk Equilibrium of Thiophene Grignard Reagents

The
Schlenk equilibrium of Grignard reagents describes the intricate
relationships between monomers, aggregates, and exchange products.
The core step of the Schlenk equilibrium, formally 2RMgX ⇌
R2Mg + MgX2, has been subject to computational studies of simple methyl
Grignards and NMR determination of thermodynamics. These studies neglect
the effect the R group may have on the accessibility of intermediates
in the Schlenk equilibrium. In this study, computational reaction
discovery tools were employed to thoroughly search the chemical space
for feasible dimerizations and pathways to ligand exchange for thiophene
Grignards. Three bridged dimers, μ-(Cl, C), μ-(Cl, Cl),
and μ-Cl, were found to be vital intermediates, which are stabilized
by π-interactions involving the thiophene group. These dimers
are approximately as thermodynamically stable as the Grignard monomers
and its ligand exchange products, and therefore, their reactivity
should be considered when examining mechanisms for aryl Grignard or
cross-coupling reactions.

Grignard试剂的Schlenk平衡描述了单体、聚集体及其交换产物之间错综复杂的关系。Schlenk平衡的核心步骤，即2RMgX ⇌ R2Mg + MgX2，已受到对简单甲基Grignard试剂的计算研究以及热力学NMR测定的关注。然而，这些研究忽略了R基团可能对Schlenk平衡中中间体可及性的影响。在本研究中，我们采用了计算反应发现工具，对化学空间进行了全面搜索，以寻找可能的二聚化途径和硫杂芳烃Grignard试剂的配体交换路径。发现了三种桥连二聚体，分别为μ-(Cl, C)、μ-(Cl, Cl)和μ-Cl，它们作为关键中间体，其稳定性得益于涉及硫杂芳烃基团的π-相互作用。这些二聚体的热力学稳定性与Grignard单体及其配体交换产物相当，因此在考察芳基Grignard或交叉偶联反应的机理时，应考虑它们的反应性。