Multistep flow synthesis of vinyl azides and their use in the copper-catalyzed Huisgen-type cycloaddition under inductive-heating conditions

Abstract

SummaryThe multistep flow synthesis of vinyl azides and their application in the synthesis of vinyltriazoles is reported. The synthesis relies on a stable polymer-bound equivalent of iodine azide that serves to carry out 1,2-functionalization of alkenes in a telescope flow protocol. The intermediate 2-iodo azides are subjected to a DBU-mediated polymer-supported elimination step yielding vinyl azides in good yield. The third step involves the formation of vinyl triazoles by a copper-catalyzed Huisgen-"click" cycloaddition. The required heat is generated by electromagnetic induction based on copper. Copper serves both as heatable as well as catalytically active packed-bed material inside the flow reactor.

Flow chemistry approaches directed at improving chemical synthesis

“…A flow stream of the corresponding aldehyde along with the Bestmann-Ohira reagent were combined with a secondary stream containing the base, potassium tert -butoxide, and progressed into a heated flow 10 coil. The flow stream upon exiting the reactor coil was then directed into a cartridge of immobilized benzylamine to remove excess aldehyde, followed by a sulfonic acid resin to quench the base and protonate any phosphoric residues.…”

Aminopropyl-silica-supported Cu nanoparticles: An efficient catalyst for continuous-flow Huisgen azide-alkyne cycloaddition (CuAAC)

“…The combination of supported Cu-based catalysts and flow reactor technologies represents a step forward in terms of reliability, time, safety, and costs over traditional batch reaction conditions. Recently, considerable efforts in this direction have been devoted to the preparation of innovative Cu-based catalysts by using different strategies to perform CuAAC in flow [31][32][33][34][35][36][37][38]. However, the development of highly recyclable heterogeneous systems with a copper contamination content into the final product at the acceptable levels still remains a challenge [35].…”

Continuous flow chemistry: a discovery tool for new chemical reactivity patterns

“…The positive impact of continuous flow chemistry on chemical processes is well studied and has been covered by many review articles. 1 The main benefits which are frequently cited are the improved heat and mass transfer, [2][3][4] greater reaction control, 5 the ease of heating solvents above their boiling point, 6 higher safety when dealing with reactive and hazardous intermediates 7 and relative simplicity of their automation and telescoping of multistep reactions. 8,9 Together these lead to overall process intensification.…”