Department of Chemistry , University of California , One Shields Avenue , Davis , California 95616 , United States.
J Org Chem. 2019 Feb 1;84(3):1126-1138. doi: 10.1021/acs.joc.8b02389. Epub 2018 Dec 24.
The hydrogen-bonding activation for 66 organocatalysts has been quantified using a P NMR binding experiment with triethylphosphine oxide (TEPO). Diverse structural classes, including phenols, diols, silanols, carboxylic acids, boronic acids, and phosphoric acids, were examined with a variety of steric and electronic modifications to understand how the structure and secondary effects contribute to hydrogen-bonding ability and catalysis. Hammett plots demonstrate high correlation for the Δδ P NMR shift to Hammett parameters, establishing the ability of TEPO binding to predict electronic trends. Upon correlation to catalytic activity in a Friedel-Crafts addition reaction, data demonstrate that P NMR shifts correlate to catalytic activity better than p K values. Boronic acids were investigated, and P NMR binding experiments predicted strong hydrogen-bonding ability, for which catalytic activity was confirmed, resulting in the greatest rate enhancement observed in the Friedel-Crafts addition of all organocatalysts studied. A detailed investigation supports that boronic acid activation proceeds through hydrogen-bonding interactions and not coordination with the Lewis acidic boron center. Using P NMR spectroscopy offers a simple and rapid tool to quantify and predict hydrogen-bonding abilities for the design and applications of new organocatalysts and supramolecular synthons.
已使用三乙基氧化膦（TEPO）的 P NMR 结合实验对 66 种有机催化剂的氢键活化作用进行了量化。研究了包括酚类、二醇类、硅醇类、羧酸类、硼酸类和磷酸类在内的各种结构类别，并对其进行了各种空间位阻和电子修饰，以了解结构和次级效应如何有助于氢键能力和催化作用。Hammett 图证明了 Δδ P NMR 位移与 Hammett 参数之间具有高度相关性，从而确立了 TEPO 结合预测电子趋势的能力。将其与弗里德尔-克拉夫茨加成反应中的催化活性相关联时，数据表明 P NMR 位移比 p K 值更能很好地关联催化活性。研究了硼酸，P NMR 结合实验预测了其具有很强的氢键能力，这一能力得到了催化活性的证实，这导致了在所研究的所有有机催化剂中观察到的弗里德尔-克拉夫茨加成中最大的速率增强。详细的研究支持硼酸的活化是通过氢键相互作用而不是与路易斯酸性硼中心的配位进行的。使用 P NMR 光谱学提供了一种简单而快速的工具，可用于量化和预测氢键能力，从而设计和应用新型有机催化剂和超分子合成子。
