Organocatalysis on Tap: Enantioselective Continuous Flow Processes Mediated by Solid‐Supported Chiral Organocatalysts

Abstract

Sustainability concerns are reshaping the way chemists work, not only at the stage of process design, but also when actually performing reactions. This change of paradigm is exemplified by the deployment of continuous flow techniques, which are slowly becoming a mainstream practice. Indeed, the possibility of performing catalytic processes (the flagship of sustainable chemistry) in flow presents distinctive advantages. Thus, several authors are focusing their efforts in trying to get the best of these two worlds, with the consequent challenge of finding common solutions for their respective issues. In the last years, this approach has been taken one step further with the use in flow processing of enantioselective organocatalysts, which allow the production of enantiopure compounds free of metal contaminants. Herein, we will cover the literature concerning the use of solid-supported organocatalysts for the continuous flow production of enantiomerically enriched compounds.

Chemical reaction engineering, process design and scale-up issues at the frontier of synthesis: Flow chemistry

“…Very interesting reports on the immobilization of enantioselective catalysts on solid supports, typically polymers such as polystyrene, are also presented [85].…”

High-performance monoliths in heterogeneous catalysis with single-phase liquid flow

“…39,40 We have adapted Scheme 1, since the Knoevenagel condensation has proven as adequate test reaction for heterogeneous base catalysis over the last decades and is therefore excessively used to evaluate basic catalysts, typically in batch mode. 41 Although heterogeneous organocatalysis in continuous-flow mode (also with silica supports) receives increased attention, [42][43][44] reports on the Knoevenagel reaction with fixed catalyst supports (porous-layer open-tubular design, monoliths, particulate beds) are relatively scarce. 16,17,[45][46][47][48][49][50][51][52][53] In both modes, however, the analysis of reaction products has so far almost exclusively been conducted off-line by gas chromatography.…”

From Immobilization to Catalyst Use: A Complete Continuous‐Flow Approach Towards the Use of Immobilized Organocatalysts

“…Despite the exponential growth of the field of asymmetric organocatalysis in the last decades and the advantages of merging it with flow chemistry, this area still remains little explored. In recent years, a small group of homogeneous and heterogeneous asymmetric reactions were successfully conducted under continuous‐flow conditions, employing certain organocatalysts and modes of catalyst activation . Nevertheless, one of the main limitations of these processes is the rapid deactivation of organocatalysts, reducing the efficiency of the transformations and impeding large‐scale application.…”