Immobilization of Functionalized epi-Cinchonine Organocatalysts on Controlled Porous Glass Beads: Applications in Batch and ­Continuous Flow

Abstract

A well-known Squaramide-Cinchonine organocatalyst was immobilized in a controlled way onto three types of commercial porous glass beads EziGTM (EziG OPAL, EziG Amber and EziG Coral) and applied in asymmetric Michael reactions. The performance of the immobilized catalysts was evaluated under batch and continuous flow conditions showing promising results in both approaches. In batch reactions, 0.8 and 1.6 mol% of the immobilized cinchonine-squaramide provided the products with excellent yields (up to 99%) and enantioselectivities (up to 99% ee). These excellent results were also verified in the case of continuous flow reactions, where also 0.8 and 1.6 mol% of the catalyst immobilized onto the glass beads afforded the product with extraordinary yields (up to 99%) and very high enantioselectivities (up to 97% ee). The immobilized catalysts could be recycled (up to 7 cycles) using both approaches.

Sustainable Organocatalyzed Enantioselective Catalytic Michael Additions in Betaine-Derived Deep Eutectic Solvents

“…We compared their performance in both batch and flow systems. 12 In this paper we report our studies on immobilized cinchona-squaramide catalysts in three different DESs, focusing on both catalytic activity and enantioselectivity of the organocatalyst and its recyclability over several reaction cycles.…”

Stereoselective Catalytic Synthesis of Bioactive Compounds in Natural Deep Eutectic Solvents (NADESs): A Survey across the Catalytic Spectrum

“…In fact, prior to 2016, there were no reports on the application of NADES to support organocatalysis [10], and the expectations were very high. More recently, our group successfully immobilized cinchona-squaramides to sizecontrolled porous glass beads and effectively used them in Michael additions of acetylacetone and methyl 2-oxocyclopentane-1-carboxylate to trans-β-nitrostyrene [17]. We further showed the application of this catalyst in the same reactions, but using NADES systems [18].…”

“…Scheme 1. Examples of Michael reactions with the Rawal Organocatalyst conducted in betaine-derived NADESs [17,18].…”

“…This phenomenon is not uncommon, and in fact both base and acid catalyzed reactions Scheme 1. Examples of Michael reactions with the Rawal Organocatalyst conducted in betainederived NADESs [17,18].…”

Asymmetric Additions Empowered by OrganoCatalysts, Metal Catalysts, and Deep Natural Eutectic Solvents (NADES)

“…In more recent times, Chiratecnics, in collaboration with the University of E ́vora, has developed immobilized versions of the Rawal Cinchona-Squaramide catalyst, via immobilization to special controlled porous glass beads known as EziG (developed by EnginZyme in Sweden), which were successfully applied to Michael addition reactions in both batch and flow chemistry. 33 The immobilization of organocatalysts to supports is an important undertaking considering that in many cases, the catalysts are expensive (due to lengthy reaction steps and the high loads that are required (10−20 mol %)), and from an industrial point of view, this approach makes sense to cut costs. 34 The 1,2,3-triazole linker (derived from the highly efficient copper-catalyzed azide alkyne reaction 35 ) has been used frequently for the immobilization of organocatalysts to various supports and used subsequently in continuous flow procedures.…”