Generation and Utilization of Sulfur(VI) Fluoride Exchange (SuFEx) Hubs

Our previous work dealt with aryl fluorosulfate synthesis by means of sulfuryl fluoride (SO2F2) gas, which was generated and used in a two chamber reactor. The fluorosulfation reaction was based on the 2014 Sharpless report, were it was shown that the SVI—F bond was selectively substituted with phenol nucleophiles. In this project, we aim to develop a similar method in which triflyl fluoride (TfF) is generated in a two-chamber system, to prepare aryl triflates from phenol starting materials. The specific goals are to provide a convenient triflation method which is an improvement upon existing procedures in terms of nucleophile selectivity, water tolerability and ease of set-up. In addition, we reported an efficient two-chamber process that enables safe and efficient ex situ processing of thiazyl trifluoride gas (NSF3) as a new type of SuFEx hub to selectively synthesize a range of mono- and di-substituted derivatives, including unsymmetrical disubstituted thiazynes with phenolic and amine substituents. Finally, we provided an efficient synthetic method to aryl triflimidate esters via SuFEx chemistry using the newly developed SuFEx hub—trifluoromethanesulfonimidoyl (triflimidoyl) fluorides (CF3SO(NR)F), which are aza-analogous of CF3SO2F SuFEx hub. These interesting three-dimensional SuFEx hubs with potential chiral character enabled us to test their unknown biological properties in Activity-Based Protein Profiling (ABPP). Moreover, to improve the covalent reaction between the above-mentioned SuFEx hubs and protein sites in ABPP, another new class of Sulfur Triazole Exchange (SuTEx) hubs was developed.