A Modular, Argon-Driven Flow Platform for Natural Product Synthesis and Late-Stage Transformations

Abstract

A modular flow platform for the synthesis of natural products and their analogs was designed. To access different reaction setups with a maximum of flexibility, interchangeable 3D-printed components serve as backbone. By switching from conventional liquid-to gas-driven flow, reagent and solvent waste is minimized which translates into an advantageous sustainability and economy profile. To enable inert conditions, practical "Schlenk-in-flow" techniques for the safe handling of oxygen-and moisture sensitive reagents were developed. Adopting these techniques, reproducible transformations in natural product synthesis were achieved. File list (2) download file view on ChemRxiv manuscript_Heretsch_CA.pdf (585.79 KiB) download file view on ChemRxiv SI_Heretsch.pdf (7.03 MiB)

Direct Photocatalyzed Hydrogen Atom Transfer (HAT) for Aliphatic C–H Bonds Elaboration

“…In another instance, a similar chlorine source was used for the chlorination of (+)-sclareolide ( 84.1 ) under flow conditions (Scheme ). Interestingly, the authors designed a “Schlenk-in-flow” technique for the safe handling of oxygen- and moisture-sensitive reagents, where argon is used instead of solvent to drive reagents through the tubing. Doing so, distribution phenomena are suppressed, which allowed saving both reagents and solvent.…”

Technological Innovations in Photochemistry for Organic Synthesis: Flow Chemistry, High-Throughput Experimentation, Scale-up, and Photoelectrochemistry

“…A modular, continuous-flow platform was reported by Christmann, Heretsch, and co-workers for the photomediated late-stage functionalization of natural products (Scheme ). Sclareolide was chosen as the natural product on which to perform the TBADT-mediated transformation using the previously reported chlorinating agent Me 4 - N -chlorosuccinimide (Me 4 NCS). The reaction mixture flowed through FEP tubing (0.79 mm ID, 2.0 mL) and was then irradiated with LEDs (365 nm).…”

Trendbericht Organische Chemie 2022

“…109) Kirschnig ermöglichte dies die trimerisierende Oxidation und anschließende Thermolyse von Cycloalkanonen zu Macrolactonen, 110) und Christmann und Heretsch verbesserten mit einem Schlenk-in-Flow-Reaktor Ausbeute und Reproduzierbarkeit kritischer Schritte von Naturstoffsynthesen. 111) Dass automatisierte Flowsynthese sich auch für mehrstufige Synthesen eignet, zeigten die Herstellung von Deoxymonosaccharidbausteinen, 112) des Anti-HIV-Medikaments Stavudin (149) 113) und des Leishmaniasis-Medikaments Miltefosin 114) .…”