Organocatalysis and catalyst aggregation: a study using the asymmetric synthesis of benzofuranones as a test reaction. Issue 38 (21st September 2018)

• Record Type: Journal Article
• Authors: Salvio, Riccardo; Massaro, Luca; Puglisi, Antonio; Angelini, Lucrezia; Antenucci, Achille; Placidi, Simone; Sciubba, Fabio; Galantini, Luciano; Bella, Marco
• Is Part Of: Organic & biomolecular chemistry. Volume 16:Issue 38(2018)
• Page Start: 7041
• Page End: 7049
• Publication Date: 2018-09-21
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c8ob01772g
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : An aggregation phenomenon involving Cinchona alkaloid derivatives deeply affects the performance of the catalyst in an organocatalytic process – a mechanistic study. Abstract : A common problem encountered in enantioselective organocatalysis is the aggregation of the catalyst, which can result in a relevant decrease of the efficiency and selectivity of the process. In the asymmetric synthesis of chiral benzofuranones, recently reported by us, we noted a remarkable increase of the reaction yield upon the addition of one of the reagents in a portionwise manner rather than in a single addition. We investigated this phenomenon by several experimental techniques such as 1D and 2D NMR experiments, UV-Vis spectroscopy, circular dichroism and dynamic light scattering. In addition, we studied the kinetic profile of this reaction using a simple numerical model and carried out in silico investigations. All these different approaches point to the conclusion that in the reaction medium a supramolecular polymerization/aggregation phenomenon, based on weak interactions, occurs and such a process is promoted by a quinone, which is one of the reagents of the benzofuranone synthesis. The portionwise mode of addition is a known strategy which can improve the performance of many synthetic procedures and this strategy is commonly adopted on account of empirical experience. However, our results provide an explanation, based on a chemical kinetic model, of the reason why the portionwise addition affects in such a dramatic way the yield of the benzofuranone synthesis catalyzed by Cinchona alkaloids.