Catalyst-free, scalable heterocyclic flow photocyclopropanation

Industrial process development is driven by several factors, including safety, cost, robustness and environmental aspects. However, attempts to establish aryl diazo esters - which are highly valued in academic research for their reactivity as carbene precursors - in the chemical industry have been l...

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Bibliographic Details
Published in:Green chemistry : an international journal and green chemistry resource : GC 2021-08, Vol.23 (17), p.6366-6372
Main Authors: Klöpfer, Viktor, Eckl, Robert, Floß, Johannes, Roth, Philippe M. C, Reiser, Oliver, Barham, Joshua P
Format: Article
Language:English
Subjects:
Biodegradability
Biodegradation
Catalysts
Chemical industry
Continuous flow
Crystallography
Design of experiments
Environmental aspects
Esters
Green chemistry
Industrial safety
Intermediates
Photolysis
Productivity
Safety
Sustainability
Toxicity
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Summary:Industrial process development is driven by several factors, including safety, cost, robustness and environmental aspects. However, attempts to establish aryl diazo esters - which are highly valued in academic research for their reactivity as carbene precursors - in the chemical industry have been limited by their explosivity and toxicity. Their catalyst-free photolysis in continuous flow improves safety, sustainability and scalability compared to batch reactions. Herein, we report the continuous flow catalyst-free photocyclopropanation of heterocycles in up to grams per h productivity in a non-chlorinated, biodegradable solvent. Highly-functionalized cyclopropanated products are key intermediates in the synthesis of drugs and pharmaceutically-relevant compounds. Optimal conditions and process understanding were obtained by a Design of Experiments approach. In comparison with a large scale batch experiment, continuous flow conditions improved yield, productivity and process safety. Visible light continuous flow photocyclopropanation of heterocyclic compounds is reported in a non-chlorinated biodegradable solvent. Design of Experiments optimization was used to arrive at optimal conditions that are safe, sustainable and scalable.
ISSN:1463-9262
1463-9270
DOI:10.1039/d1gc01624e