The utilization of copper flow reactors in organic synthesis

Abstract

The use of flow chemistry techniques has flourished over the past decade, with the field expanding to include the use of copper flow reactors in bench-top organic synthesis in recent years. These reactors are available in a variety of forms and possess a number of advantages over their batch reaction counterparts, in terms of both safety and yield. This review will highlight the current research employing copper flow reactors, such as 1,3-dipolar cycloadditions ('click' chemistry), macrocyclizations (via 'click' chemistry), Sonogashira C-C couplings, Ullmann couplings, decarboxylations, and other reported findings.

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

“…Copper flow reactors were applied to many different reactions thanks to the valuable heat exchange properties [119]. Examples are 1,3-dipolar cycloadditions, macrocyclizations, Sonogashira coupling, Ullmann-type reactions and decarboxylations.…”

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

“…Several [2 + 3] cycloadditions have been developed in continuous-flow over the years, and some of these have been recently reviewed, such as the copper-catalysed version of Huisgen reaction [457][458][459]. The latter consists of a 1,3-dipolar cycloaddition between an azide and alkyne to form the 1,2,3-triazoles as a mixture of 1,4-and 1,5-adducts.…”

“…Immobilisation of copper catalysts has been further developed; alongside the usage of copper coils, already described by Tranmer and Fülöp [457,458,467,468], other new heterogeneous formats have also been reported [469][470][471][472][473]. As an example, in 2020, a polymer-supported tris-triazole ligand was prepared and utilised for Cu immobilisation [474].…”

Recyclable supported Pd-NHC catalytic systems for the copper-free Sonogashira cross-coupling in flow

“…Although several approaches have been developed for metal-catalysed C-C cross coupling reactions in flow, [27][28][29][30][31][32][33][34] the number of examples concerning specifically the Sonogashira reaction using flow methodology and a recyclable catalyst, is very small and among those most involve the use of aryl iodides as substrates. [35][36][37][38] Concerning the use of aryl bromides as substrates for Sonogashira coupling under flow, a small number of examples, involving quite different strategies for catalyst immobilization, are reported in the literature and only two that employ a recyclable catalyst. In 2003 Plenio reported the immobilisation of the polymer-tagged palladium catalysts in a stationary solvent for the Sonogashira cross coupling of different aryl bromides and phenyl acetylene.…”