Fast flow-chemistry set-up facilitates sulfur-fluoride click chemistry

A fast flow chemistry method makes the production of sulfuryl fluoride quicker and safer. This gaseous reagent is useful in the synthesis of click-ready reagents, then easily functionalised into a myriad of chemical compounds, including peptides and proteins. Most reactions take place in less than two minutes, in a site-selective manner – a great opportunity for high-throughput experiments and drug discovery.

Sulfuryl fluoride is a surprisingly useful reagent in click-chemistry reactions, in particular the sulfur(VI) fluoride exchange, also known as SuFEx. ‘SuFEx chemistry is very similar but orthogonal to the more famous azide–alkyne click chemistry,’ explains Nina Hartrampf, an expert in flow synthesis for chemical biology applications in the University of Zurich, Switzerland. ‘The reaction proceeds under mild reaction conditions and often yields clean transformations,’ she adds. In SuFEx reactions, ‘two nucleophiles can react with sulfuryl fluoride and ultimately the SO₂ moiety ultimately serves as a very small linker’ between the clicked fragments. ‘SuFEx click reactions are often used for the generation of libraries in medicinal chemistry [and] recently they have also found applications in the functionalisation of biomolecules such as peptides and proteins,’ says Hartrampf. Another attractive aspect of SuFEx reactions is versatility – they work with alcohols and amines natively, without the need for azides or alkynes, which is the case in copper-catalysed click reactions.