Tichá Iveta Chena, Hybelbauerová Simona, Jindřich Jindřich
Department of Organic Chemistry, Faculty of Science, Charles University, Hlavova 8, 128 43, Prague 2, Czech Republic.
Department of Teaching and Didactics of Chemistry, Faculty of Science, Charles University, Hlavova 8, 128 43, Prague 2, Czech Republic.
Beilstein J Org Chem. 2019 Apr 1;15:830-839. doi: 10.3762/bjoc.15.80. eCollection 2019.
The preparation of new organocatalysts for asymmetric syntheses has become a key stage of enantioselective catalysis. In particular, the development of new cyclodextrin (CD)-based organocatalysts allowed to perform enantioselective reactions in water and to recycle catalysts. However, only a limited number of organocatalytic moieties and functional groups have been attached to CD scaffolds so far. Cinchona alkaloids are commonly used to catalyze a wide range of enantioselective reactions. Thus, in this study, we report the preparation of new α- and β-CD derivatives monosubstituted with cinchona alkaloids (cinchonine, cinchonidine, quinine and quinidine) on the primary rim through a CuAAC click reaction. Subsequently, permethylated analogs of these cinchona alkaloid-CD derivatives also were synthesized and the catalytic activity of all derivatives was evaluated in several enantioselective reactions, specifically in the asymmetric allylic amination (AAA), which showed a promising enantiomeric excess of up to 75% ee. Furthermore, a new disubstituted α-CD catalyst was prepared as a pure AD regioisomer and also tested in the AAA. Our results indicate that (i) the cinchona alkaloid moiety can be successfully attached to CD scaffolds through a CuAAC reaction, (ii) the permethylated cinchona alkaloid-CD catalysts showed better results than the non-methylated CDs analogues in the AAA reaction, (iii) promising enantiomeric excesses are achieved, and (iv) the disubstituted CD derivatives performed similarly to monosubstituted CDs. Therefore, these new CD derivatives with cinchona alkaloids effectively catalyze asymmetric allylic aminations and have the potential to be successfully applied in other enantioselective reactions.
用于不对称合成的新型有机催化剂的制备已成为对映选择性催化的关键阶段。特别是，新型环糊精（CD）基有机催化剂的开发使得在水中进行对映选择性反应以及催化剂的循环利用成为可能。然而，到目前为止，仅有有限数量的有机催化部分和官能团被连接到CD支架上。金鸡纳生物碱通常用于催化多种对映选择性反应。因此，在本研究中，我们报道了通过铜催化的叠氮-炔环加成（CuAAC）点击反应在α-和β-环糊精的主环上用金鸡纳生物碱（辛可宁、辛可尼定、奎宁和奎尼丁）单取代制备新型衍生物。随后，还合成了这些金鸡纳生物碱-CD衍生物的全甲基化类似物，并在几种对映选择性反应中评估了所有衍生物的催化活性，特别是在不对称烯丙基胺化反应（AAA）中，该反应显示出高达75% ee的有前景的对映体过量。此外，制备了一种作为纯AD区域异构体的新型二取代α-环糊精催化剂，并也在AAA反应中进行了测试。我们的结果表明：（i）金鸡纳生物碱部分可通过CuAAC反应成功连接到CD支架上；（ii）在AAA反应中，全甲基化的金鸡纳生物碱-CD催化剂比未甲基化的CD类似物表现出更好的结果；（iii）实现了有前景的对映体过量；（iv）二取代的CD衍生物与单取代的CD表现相似。因此，这些带有金鸡纳生物碱的新型CD衍生物有效地催化不对称烯丙基胺化反应，并有可能成功应用于其他对映选择性反应。
