Occhipinti Giovanni, Bjørsvik Hans-René, Jensen Vidar R
Department of Chemistry, University of Bergen, Allégaten 41, N-5007 Bergen, Norway.
J Am Chem Soc. 2006 May 31;128(21):6952-64. doi: 10.1021/ja060832i.
A quantitative structure-activity relationship (QSAR) model is presented in which both the independent and dependent (response) variables are derived from density functional theory (DFT) calculations on a large set of 14-electron complexes, LCl(2)Ru=CH(2), with different dative ligands, L. The multivariate model thus correlates the properties of the 14-electron complexes with a calculated measure of activity, with modest computational cost, and reproduces the experimental order of activity for the Grubbs ruthenium catalysts for olefin metathesis. The accuracy and applicability of the model is to a large extent due to the use of highly specific geometric and electronic molecular descriptors which establish a direct connection between activity and chemically meaningful donor ligand properties. The ligands that most efficiently promote catalytic activity are those that stabilize the high-oxidation state (+4) metallacyclobutane intermediate relative to the ruthenium-carbene structures dominating the rest of the reaction pathway. Stabilization of the intermediate is ensured, among others, through ligand-to-metal sigma donation, whereas metal-to-ligand pi back-donation destabilizes the intermediate and lowers catalytic activity. A bulky dative ligand drives the reaction toward the less sterically congested metallacyclobutane species and thus contributes to catalytic activity. The multivariate model and the high-level descriptors furthermore provide practical handles for catalyst development as exemplified by the suggestion of several new donor ligands predicted to give more active and functional group tolerant ruthenium-based catalysts. The present strategy holds great promise for broader screenings of olefin metathesis catalysts as well as for development of homogeneous transition metal catalysts in general.
本文提出了一种定量构效关系（QSAR）模型，其中自变量和因变量（响应变量）均源自对一大组含有不同给体配体L的14电子配合物LCl₂Ru=CH₂进行的密度泛函理论（DFT）计算。因此，该多变量模型将14电子配合物的性质与计算得到的活性度量相关联，计算成本适中，并重现了用于烯烃复分解反应的格拉布催化剂的实验活性顺序。该模型的准确性和适用性在很大程度上归因于使用了高度特异性的几何和电子分子描述符，这些描述符在活性与具有化学意义的供体配体性质之间建立了直接联系。最有效地促进催化活性的配体是那些相对于主导反应路径其余部分的钌卡宾结构稳定高氧化态（+4）金属环丁烷中间体的配体。中间体的稳定化尤其通过配体到金属的σ给电子作用来确保，而金属到配体的π反馈给电子作用会使中间体不稳定并降低催化活性。体积较大的给体配体促使反应朝着空间位阻较小的金属环丁烷物种进行，从而有助于催化活性。此外，多变量模型和高级描述符为催化剂开发提供了实际的方法，例如预测了几种新的供体配体，有望得到更具活性且对官能团耐受性更高的钌基催化剂。本策略对于更广泛地筛选烯烃复分解催化剂以及总体上开发均相过渡金属催化剂具有很大的前景。
