Lu Jingru, Celuszak Holly, Paci Irina, Leitch David C
Department of Chemistry, University of Victoria, 3800 Finnerty Rd., Victoria, BC V8P 5C2, Canada.
Chemistry. 2024 Nov 7;30(62):e202402282. doi: 10.1002/chem.202402282. Epub 2024 Oct 14.
Quantitative molecular structure-reactivity models are useful for generating predictions to guide synthesis design, and in formulating and testing mechanistic hypotheses. We report an expanded multivariate linear regression (MLR) model for the rate of (hetero)aryl (pseudo)halide oxidative addition to LPd(0), here exemplified by Pd(PCy). This builds on a prior model from our group, with additional substrate classes (aryl chlorides and iodides) and reaction solvents (THF, toluene, THF/DMF mixture). Overall solvent effects across the entire substrate set are minimal under these conditions, enabling a unified MLR model without introduction of new molecular descriptors beyond the original five. Examining the mechanistic origin of the two molecular electrostatic potential (ESP) descriptors led to generation of a simpler, four descriptor model that is suitable for aryl halides, but not for 2-halopyridines. Using this model we identified a mechanistic outlier, 2-pyridyl triflate, which undergoes a nucleophilic displacement oxidative addition that does not involve the adjacent nitrogen atom. Finally, we discuss the relationship between C-X bond strength and oxidative addition rates, and compare the intrinsic bond strength index (IBSI) to bond dissociation enthalpy (BDE) as a bond strength descriptor.
定量分子结构-反应性模型对于生成预测以指导合成设计以及制定和检验机理假设非常有用。我们报告了一种扩展的多元线性回归（MLR）模型，用于描述（杂）芳基（拟）卤化物向LPd(0)的氧化加成速率，此处以Pd(PCy)为例。该模型基于我们小组之前的一个模型，增加了底物类别（芳基氯化物和碘化物）和反应溶剂（四氢呋喃、甲苯、四氢呋喃/二甲基甲酰胺混合物）。在这些条件下，整个底物集的总体溶剂效应最小，无需引入除原来五个之外的新分子描述符即可建立统一的MLR模型。研究两个分子静电势（ESP）描述符的机理起源，得到了一个更简单的四描述符模型，该模型适用于芳基卤化物，但不适用于2-卤代吡啶。使用该模型，我们确定了一个机理异常值，即2-吡啶基三氟甲磺酸酯，它经历了不涉及相邻氮原子的亲核取代氧化加成。最后，我们讨论了C-X键强度与氧化加成速率之间的关系，并比较了作为键强度描述符的固有键强度指数（IBSI）和键解离焓（BDE）。
