Department of Nuclear Medicine, Cyclotron Research Center, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-712, Korea.
Chemistry. 2012 Mar 26;18(13):3918-24. doi: 10.1002/chem.201102455. Epub 2012 Feb 16.
Herein, we report the promising use of n-oligoethylene glycols (oligoEGs) as mutifunctional promoters for nucleophilic-substitution reactions employing alkali metal salts. Among the various oligoEGs tested, pentaethylene glycol (pentaEG) had the most efficient catalytic activity. In particular, when compared with other nucleophiles examined, a fluorine nucleophile generated from CsF was significantly activated by the pentaEG promoter. We also performed various facile nucleophilic-displacement reactions, such as the halogenation, acetoxylation, thioacetoxylation, nitrilation, and azidation of various substrates with potassium halides, acetate, thioacetate, cyanide, and sodium azide, respectively, in the presence of the pentaEG promoter. All of these reactions provided their desired products in excellent yields. Furthermore, the combination of pentaEG and a tert-alcohol medium showed tremendous efficiency in the nucleophilic-displacement reactions (fluorination and methoxylation) of base-sensitive substrates with basic nucleophiles (cesium fluoride and potassium methoxide, respectively). The catalytic role of oligoEGs was examined by quantum-chemical methods. The oxygen atoms in oligoEGs were found to act as Lewis bases on the metal cations to produce the "flexible" nucleophile, whereas the two terminal hydroxy (OH) groups acted as "anchors" to orientate the nucleophile and the substrate into an ideal configuration for the reaction.
本文报道了 n-聚乙二醇（OligoEG）作为亲核取代反应的多功能促进剂的应用前景，其中涉及碱金属盐。在所测试的各种 OligoEG 中，五乙二醇（PentaEG）具有最高的催化活性。特别是与所研究的其他亲核试剂相比，CsF 生成的氟亲核试剂在 PentaEG 促进剂的作用下被显著激活。我们还进行了各种简便的亲核取代反应，如各种底物的卤化、乙酰化、硫代乙酰化、腈化和叠氮化反应，分别使用钾卤化物、醋酸盐、硫代醋酸盐、氰化物和叠氮化钠作为亲核试剂，在 PentaEG 促进剂的存在下进行。所有这些反应都以优异的产率得到了所需的产物。此外，PentaEG 和叔醇介质的组合在与碱性亲核试剂（氟化铯和甲醇钾）反应时，对碱性敏感底物的亲核取代反应（氟化和甲氧基化）显示出巨大的效率。通过量子化学方法研究了 OligoEG 的催化作用。发现 OligoEG 中的氧原子在金属阳离子上充当路易斯碱，生成“灵活”的亲核试剂，而两个末端的羟基（OH）基团充当“锚”，将亲核试剂和底物定向到反应的理想构型中。
