Continuous flow organometallic catalysis: new wind in old sails

Abstract

Organometallic catalysis is a powerful tool for chemical synthesis, and the field still evolves at a high pace continuously improving efficiencies and opening up new possibilities. However, despite increasing use in specialty and fine chemical production issues of catalyst recovery still hamper broader application and prevent tapping the full potential of this technology on industrial scale. Even though scientists have tackled this problem for decades practicable methods remained scarce. In this contribution we analyse the major challenges of performing organometallic catalysis in continuous flow from a conceptual point of view, and exemplify for recently developed concepts based on near- and supercritical fluids how the integration of molecular and engineering principles can offer new solutions to this persistent problem.

Exploiting the C-H bond in metal catalyzed C-C bond forming reactions

“…We also investigated systems in which C(sp 3 )-H and C(sp 2 )-H bonds can be exchanged. Interestingly, in all these examples we found the highest deuterium content in the aliphatic positions (35,(38)(39)(40). Additionally, indole derivatives can be deuterated under microwave irradiation as well, which shortens the reaction time from 3 hours to 15 minutes.…”

“…Additionally, complete reaction sequences towards complex molecules have been carried out under flow conditions. [39][40][41] However, direct arylations have not been included in this reaction portfolio so far. Hence we set out to develop such a protocol.…”

Beyond Organometallic Flow Chemistry: The Principles Behind the Use of Continuous-Flow Reactors for Synthesis

“…Furthermore, solvents or gasses can be heated and pressurized above their critical point furnishing supercritical reaction conditions. [99][100][101] Supercritical conditions provide reduced viscosity and interfacial tension, improved diffusivities and increased gas solubility.…”

Continuous‐Flow Synthesis and Derivatization of Aziridines through Palladium‐Catalyzed C(sp3)−H Activation

“…[2,3] Ac entral field in modern synthetic organic chemistry is transition-metal-catalyzed CÀHa ctivation. Thel ast 15 years have seen tremendous advances in the use of many different metal catalysts to functionalize traditionally unreactive C À H bonds;palladium salts,inparticular, have enjoyed agreat deal of success in effecting CÀHactivation reactions.…”

“…[1] Acrucial aspect of realizing this ideal is the effective crossover from fundamental chemistry advances to process engineering.I ti sn oticeable that the transition of novel catalytic transformations of potential industrial interest into continuous flow processes is often slow owing to the inherent complexity of the reaction systems.W ith often limited mechanistic understanding of new reactions,i ti s rarely straightforward to determine the best reactor configuration or predict their behavior at scale,which can make the design of an optimal process difficult regardless of whether it is batch, semibatch, or continuous.The ultimate desired target for process chemistry is afully predictive process model that accounts for aw ide range of operating conditions and scale effects.H owever,t he development of such models for complex reactions represents as ignificant methodological challenge. [2,3] Ac entral field in modern synthetic organic chemistry is transition-metal-catalyzed CÀHa ctivation. Thel ast 15 years have seen tremendous advances in the use of many different metal catalysts to functionalize traditionally unreactive C À H bonds;palladium salts,inparticular, have enjoyed agreat deal of success in effecting CÀHactivation reactions.…”