Spiaggia Fabio, Uccello Barretta Gloria, Iuliano Anna, Baldassari Carlo, Aiello Federica, Balzano Federica
Department of Chemistry and Industrial Chemistry, University of Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy.
National Research Council, Institute for Chemical and Physical Processes (CNR-IPCF), Via G. Moruzzi 1, 56124 Pisa, Italy.
Molecules. 2024 May 19;29(10):2389. doi: 10.3390/molecules29102389.
A squaramide-based organocatalyst for asymmetric Michael reactions has been tested as a chiral solvating agent (CSA) for 26 carboxylic acids and camphorsulfonic acid, encompassing amino acid derivatives, mandelic acid, as well as some of its analogs, propionic acids like profens (ketoprofen and ibuprofen), butanoic acids and others. In many cases remarkably high enantiodifferentiations at H, C and F nuclei were observed. The interaction likely involves a proton transfer from the acidic substrates to the tertiary amine sites of the organocatalyst, thus allowing for pre-solubilization of the organocatalyst (when a chloroform solution of the substrate is employed) or the simultaneous solubilization of both the catalyst and the substrate. DOSY experiments were employed to evaluate whether the catalyst-substrate ionic adduct was a tight one or not. ROESY experiments were employed to investigate the role of the squaramide unit in the adduct formation. A mechanism of interaction was proposed in accordance with the literature data.
一种用于不对称迈克尔反应的基于方酰胺的有机催化剂已被测试作为26种羧酸和樟脑磺酸的手性溶剂化剂（CSA），这些羧酸包括氨基酸衍生物、扁桃酸及其一些类似物、丙酸如布洛芬类药物（酮洛芬和布洛芬）、丁酸等。在许多情况下，在氢、碳和氟原子核处观察到了显著的对映体区分。这种相互作用可能涉及质子从酸性底物转移到有机催化剂的叔胺位点，从而使有机催化剂能够预溶解（当使用底物的氯仿溶液时）或使催化剂和底物同时溶解。采用扩散排序谱（DOSY）实验来评估催化剂-底物离子加合物是否紧密。采用旋转 Overhauser 效应谱（ROESY）实验来研究方酰胺单元在加合物形成中的作用。根据文献数据提出了一种相互作用机制。
