Stereoselective organic reactions promoted by immobilized chiral catalysts in continuous flow systems

Abstract

The immobilization of the catalyst on a support with the aim of facilitating the separation of the product from the catalyst, and thus the recovery and recycling of the latter, can be regarded as an important improvement for a catalytic process. However, a system where a catalyst must not be removed from the reaction vessel is even more attractive: in continuous flow methods the immobilized catalyst permanently resides in the reactor where it transforms the entering starting materials into the desired products. The retention of the catalytic species inside the reaction vessel can be achieved by different techniques ranging from ultrafiltration through a M W-selective membrane to immobilization on different supports. In this review we will discuss the most significant examples of stereoselective reactions promoted by immobilized chiral catalysts and performed under continuous flow conditions, with particular attention to the more recent contributions of the last few years.

An efficient continuous flow process for the synthesis of a non-conventional mixture of fructooligosaccharides

“…It is worth noting that, after only 10 h of residence time, a 47.4% (w/w) of conversion was already reached and that the total amount of FOS only slightly increased in the following 10 h. A similar conversion (48% w/w) was obtained in batch after 72 h of reaction. A significant reduction of the reaction time is a typical benefit achieved on passing from batch to flow conditions, both for heterogeneous chemo-or bio-catalyzed reactions (Kirschning et al, 2006;Puglisi, Benaglia, & Chiroli, 2013).…”

Asymmetric one-pot reactions using heterogeneous chemical catalysis: recent steps towards sustainable processes

“…Accordingly, during the last fifteen years, the development of heterogeneous recyclable organocatalysts became a significant task. 16,32,[148][149][150][151][152] Moreover, several efficient organocatalysts were able to catalyse various reactions or could tolerate the presence of other catalytic species. Thus, their application in one-pot reactions also evolved rapidly.…”

“…However, oftentimes by appropriate material design, robust and stable chiral catalysts have been obtained, which allow preserved performances upon recycling, and the possibility of application in flow systems. [32][33][34] Further increase in the sustainability of the catalytic reactions may result from carrying out several reactions in a single vessel, without isolation of the intermediate products in a so-called one-pot procedure. [35][36][37][38] One-pot reactions that allow two or more bond-forming transformations under the same conditions without intervention and with subsequent transformations occurring at the functionalities resulting from a previous step, are designated domino or cascade reactions.…”

Enantioselective Organocatalysis in Microreactors: Continuous Flow Synthesis of a (S)-Pregabalin Precursor and (S)-Warfarin

“…This purification step (that is also usually required in the batch process) somehow affects the appealing of the continuous-flow process and more efforts are required to circumvent this problem. One possible solution could be represented by the use of supported catalysts, that is a well-established methodology when meso-or mini-reactors are used [18], but much less exploited in the case of microreactors [38]. The combination of an immobilized catalyst and a complete conversion of the starting material (or an easy separation of the desired product) could allow a very attractive procedure for large-scale production of interesting intermediates.…”

“…In the last few years, the use of organocatalytic chiral reactors has received considerable attention, leading to the development of different supported chiral metal-free catalysts employed in continuous-flow processes [18][19][20][21]. Also our group contributed to this field and realized packed-bed and monolithic reactors containing solid supported chiral catalysts such as cinchona derivates [22] and chiral imidazolidinones [23][24][25].…”