Jiménez Eddy I, Vallejo Narváez Wilmer E, Román-Chavarría Carlos A, Vazquez-Chavez Josue, Rocha-Rinza Tomás, Hernández-Rodríguez Marcos
Institute of Chemistry, National Autonomous University of Mexico , Circuito Exterior, Ciudad Universitaria, Del. Coyoacán, 04510 Cd. Mx., Mexico.
J Org Chem. 2016 Sep 2;81(17):7419-7431. doi: 10.1021/acs.joc.6b01063. Epub 2016 Aug 4.
Thioureas are an important scaffold in organocatalysis because of their ability to form hydrogen bonds that activate substrates and fix them in a defined position, which allows a given reaction to occur. Structures that enhance the acidity of the thiourea are usually used to increase the hydrogen-bonding properties, such as 3,5-bis(trifluoromethyl)phenyl and boronate ureas. Herein, we report the synthesis of bifunctional thioureas with a chiral moiety that include either a trifluoromethyl or methyl group. Their catalytic performance in representative Michael addition reactions was used in an effort to compare the electronic effects of the fluorination at the methyl group. The observed differences concerning yields and ee values cannot be attributed solely to the different steric environments; theoretical results indicate distinct interactions within the corresponding transition states. The calculated transition states show that the fluorinated catalysts have stronger N-H···O and C-H···F hydrogen bonds, while the nonfluorinated systems have C-H···π contacts. These results have shown that a variety of hydrogen-bonding interactions are important in determining the yield and selectivity of thiourea organocatalysis. These details can be further exploited in catalyst design.
硫脲是有机催化中的一种重要骨架，因为它们能够形成氢键，激活底物并将其固定在特定位置，从而使特定反应得以发生。增强硫脲酸度的结构通常用于提高氢键性能，如3,5-双（三氟甲基）苯基和硼酸酯脲。在此，我们报道了具有手性部分的双功能硫脲的合成，该手性部分包括三氟甲基或甲基。它们在代表性迈克尔加成反应中的催化性能被用于比较甲基氟化的电子效应。观察到的关于产率和对映体过量值的差异不能仅仅归因于不同的空间环境；理论结果表明在相应过渡态中有明显的相互作用。计算得到的过渡态表明，氟化催化剂具有更强的N-H···O和C-H···F氢键，而非氟化体系具有C-H···π接触。这些结果表明，多种氢键相互作用在决定硫脲有机催化的产率和选择性方面很重要。这些细节可在催化剂设计中进一步加以利用。
