Theoretical study on acidities of (S)-proline amide derivatives in DMSO and its implications for organocatalysis.
Theoretical study on acidities of (S)-proline amide derivatives in DMSO and its implications for organocatalysis.
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DMSO 中 (S)-脯氨酸酰胺衍生物的酸度理论研究及其对有机催化的影响。
DOI：
10.1021/jp909043a
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Jing Shi
中科院分区：
文献类型：
--
作者：
Xiong Huang;Hua;Jing Shi
脯氨酸酰胺衍生物的酸性（pK（a）值）对于理解脯氨酸基有机催化剂的催化活性是非常重要的。对这些化合物的pK（a）值的系统研究也有助于开发新的催化剂。然而，由于实验测量的困难，目前只有少数基于脯氨酸的有机催化剂的pK（a）值可用。在这项工作中，我们着手研究各种脯氨酸酰胺衍生物的pK（a）值的理论计算。对不同的理论方法进行了评价，发现B3 PW 91/6-311++G（3df，2 p）//B3 LYP/6-31+G（d）//HF//CPCM/UA 0组合方法是重现结构无关的酰胺和酰胺衍生物在DMSO中pK（a）值的最佳方法。新开发的理论模型的MAD和RMSE分别等于0.98和1.3 pK单位。该方法还首次系统地研究了脯氨酸酰胺衍生物的各种结构效应对pK（a）值的影响，如Z-异构化、远程取代和α-取代效应。本文还研究了一系列手性酰胺的pK（a）值。最后，我们应用理论方法预测了大量的脯氨酸基有机催化剂，并建立了广泛的化合物的酸度标度。
The acidities (pK(a) values) of proline amide derivatives are of great importance for understanding the catalytic activity of proline-based organocatalysts. The development of new catalysts could also benefit from the systematic study of the pK(a) values of these compounds. However, only a few pK(a) values of the proline-based organocatalysts are currently available due to the difficulty in experimentally measurements. In this work, we set out to study the pK(a) values of various proline amide derivatives with theoretical calculations. Different theoretical methods were evaluated and the combined method, B3PW91/6-311++G(3df,2p)//B3LYP/6-31+G(d)//HF//CPCM/UA0, was found to be the best one in reproducing the pK(a) values of structurally unrelated amides and amide derivatives in DMSO. The MAD and RMSE of the newly developed theoretical model equal to 0.98 and 1.3 pK units, respectively. The method also enabled the systematically study on various structural effects on pK(a) values of proline amide derivatives, such as the ZE-isomerization, remote substitution, and alpha-substitution effects, for the first time. The pK(a) values of a series of chiral amides were also studied in this work. Finally, we applied the theoretical method to predict a large number of proline-based organocatalysts and established an extensive acidity scale of the compounds.