Advances in continuous flow: from photochemistry to heterogeneous chemistry

Tea and coffee will be served after the seminar in WP 1.05

Functionalisation of C-H bonds has been a topic of study since H. J. Fenton reported his findings in 1894. Since then, organic chemists have been using organocatalysis to functionalise C-H bonds. It often requires the need of prefunctionalised starting materials to carry such activation. In recent years, the development of photoinduced processes have witnessed great progress with regards to photocyclisations and photocatalysed C-H functionalisation reactions. The limiting factor on these reactions is usually the photon density that irradiates the reagents. With the use of the 150W UV LED, we report the effect of photon density on photocycloadditions and α-tertiary primary amines.
The second part of the talk will focus on solid phase approaches to peptide synthesis (SPPS). Thanks to the implementation of continuous flow, SPPS is witnessing a new renaissance. By working in flow using a Variable Bed Flow reactor (VBFR), peptides can be synthesized more efficiently while accessing real-time data, such as UV spectra or reactor volume change. When combining both UV and reactor volume change, aggregation of peptides can be identified in the sequence. Using Glucagon-like peptide-1 (GLP-1) as example peptide, Manuel will explain how we developed anti-racemisation strategies as well as cleavage in flow, yielding a crude purity of over 80 %. Pumping a TFA cocktail at 50 oC has allowed the peptide to be cleaved in under 40 minutes, obtaining repeatable results.
The final part of the presentation will focus on different strategies to carry heterogeneous reactions in continuous flow. By packing magnesium in a VBFR, channeling of reagents is minimised, Grignard reagents can be prepared in situ from readily available reagents with full conversion.
Suspended solids in flow is typically synonym to reactor blockage but depending on the physical properties of the solid reagent, they can be handled as slurry in tubular reactors. Pd on charcoal is an excellent catalyst for hydrogenations, but due to its small particle size, it can be challenging to pack in a column without causing blockages. By pumping slurries of it up to 100 mg/ml, a 6 g/h throughput of an API intermediate was achieved in a 3-phase hydrogenation reaction.