Synthesis Of A Novel Fluorosulfuryl Transfer Reagent And Its Reactivity With Amines

The efficient introduction of S^?-F functional groups in a broad-spectrum of organic molecules remains to be the key challenge in sulfur?VI?-fluoride exchange?SuFEx?chemistry.Among the discovered S^VI-F functional groups,the fluorosulfuryl functional group?-SO₂F?has the most applications.Literatures have reported the use of sulfuryl fluoride?SO₂F₂?gas in the preparation of arylfluorosulfonates?ArO-SO₂F?from phenols?Ar-OH?and sulfamoyl fluoride?R¹R²N-SO₂F?from secondary amines?R¹R²NH?.Despite its low cost,the transport and use of sulfuryl fluoride gas are under strict regulation.The accessibility of sulfuryl fluoride for research institutes worldwide has limited the development of sulfur?VI?-fluoride exchange.This dissertation focuses on the development of a shelf-stable solid fluorosulfuryl transfer reagent,as a more accessible surrogate for sulfuryl fluoride gas.Starting from different imidazoles,a series of fluorosulfuryl imidazolium salts have been synthesized by sequential reaction with sulfuryl fluoride gas then a methylating agent.To compare their reactivity as fluorosulfuryl transfer reagent,4-benzylpiperidine reacted with these reagents and the yields of sulfamoyl fluoride products were compared.The results have shown that 1-?fluorosulfuryl?-2,3-dimethyl-1H-imidazol-3-ium trifluoromethanesulfonate had the best reactivity.Due to the simplicity of the procedure and the accessibility of the starting materials,the synthesis of the reagent was easily scaled up.Subsequently,the reactivity of this fluorosulfuryl transfer reagent towards different types of amines was shown to be superior to sulfuryl fluoride gas for both shorter reaction time and wider substrate scope.Particularly impressive was its performance in the reactions with aliphatic and aromatic primary amines.A wide range of substrates,selected from this very common class of amines,all reacted just once with the reagent stopping cleanly at the sulfamoyl fluoride stage?R-NH-SO₂F?,which had been previously inaccessible for sulfuryl fluoride.The reagent would specifically react with the primary amine in the presence of oxygen nucleophiles,demonstrating a selectivity opposite to sulfuryl fluoride gas.When triethylamine?0.5 equiv.?was added,the bisfluorosulfurylated product?R-N?SO₂F?₂?could be prepared directly from the primary amine.Finally,the reactivity of the-NHSO₂F functional group was investigated.Further transformation of this functional group as a powerful connecting hub was studied that could open up a new chemical space in sulfur???-fluorine exchange.