Exploring the chemistry of N-hydroxypyrazinones

Although industrial processes readily use reactive and dangerous gases as platform chemicals, a different picture is seen in lab-scale synthesis. The difficult-to-handle nature of gaseous reagents in combination with stringent safety requirements have posed a significant barrier for research scientists to conduct chemical reactions with gases on a regular basis.

In 2011, the Skrydstrup group launched the two-chamber reactor as a safe and user-friendly tool to employ gases in organic synthesis. In this device, a gas is released from a precursor molecule in one chamber, which subsequently diffuses to the adjacent chamber, where it is consumed in a chemical reaction. Consequently, the risk of direct contact between the operator and the gaseous reagent is completely eliminated.

In this thesis, we developed one of the most cost-efficient carbon monoxide (CO) generating systems to date, with formic acid as the CO source. In a follow-up project, this system was implemented in a two-chamber reactor for the synthesis of a novel heterocyclic scaffold via an unprecedented intramolecular carbonylative C-H activation of 1-(2-bromoaryl)-1,2,3-triazoles.

Moving away from carbon monoxide, precursor molecules for other useful gases were sought after. Due to the renewed interest in sulfuryl fluoride gas (SO2F2), we developed a straightforward protocol for its on-demand production in a two-chamber reactor to transform phenols into aryl fluorosulfates. This class of substrates is particularly interesting, either by merit of its leaving group ability or as a SuFEx click chemistry partner. Lastly, in collaboration with the Skrydstrup group, the field of CO and SO2F2 chemistry were merged to synthesize α,α-bis(trifluoromethyl) carbinols from aryl bromides and fluorosulfates.