SO2F Radical Sparkles From Sulfuryl Fluoride Gas

A practical fluorosulfonylating platform via photocatalytic imidazolium-based SO2F radical reagent has been established by organic chemists from Nanjing University at China.

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The sulfur(VI) fluoride exchange (SuFEx) chemistry that rely on the unique reactivity–stability balance of high valent organosulfur has emerged as a promising topic for the next-generation click reaction. Sulfonyl fluorides as the most widely used connective hubs of SuFEx click reaction have attracted enormous attention and find widespread applications in the fields of chemical biology, drug discovery and materials science. However, the synthesis of sulfonyl fluorides from inert sulfuryl fluoride (SO2F2) gas through a fluorosulfonyl radical (·SO2F) process has met with inevitable difficulties due to the high homolytic bond dissociation energy of the S(VI)-F bond.

Caption

Sulfuryl fluoride (SO2F2) as abundant inflammable industrial feedstock could serve as economic sulfonyl fluoride source. Sulfuryl fluoride derived fluorosulfonylating reagents are mainly electrophilic “FSO2+” synthons and have been employed for direct functionalization of different nucleophiles including organometallic reagents, phenols, amines, etc. However, the construction of diversified sulfonyl fluoride compounds was limited by single electrophilic reaction pattern and hindered multifunctionalization of SO2F2 and derivatives. In contrast, adopting a radical synthesis strategy can overcome the limitations of electrophilic fluorosulfonylation and expand the scope of application of sulfonyl fluoride. However, the generation of fluorosulfonyl radical (·SO2F) from inert SO2F2 gas has met with inevitable difficulties due to the relatively small magnetic/quadrupole moments and the high homolytic bond dissociation energy of the S(VI)-F bond (BDE = 90.5±4.3 kcal/mol)1 (Fig. 1a).

A practical procedure for the bench-stable redox-active ·SO2F agent from inexpensive fluorine source would provide appropriate solution to the long-standing issue of radical fluorosulfonylation. The imidazolium sulfonate cationic salt that developed in our lab has been successfully applied for the activation of triflic acid and arylsulfonates to access ·SO2CF3 and ArS· radicals. (Nat. Commun. 2020, 11, 2572 , Chem. Sci. 2021, 12, 2509-2514.) It is speculated that the cationic benzimidazole salt could harness the highly electrophilic SO2F to forge a bench-stable redox-active (Het)N-SO2F reagent (Fig. 1b). (Angew. Chem. Int. Ed. 2018, 57, 13795-13799) The positive charge of the resulting benzimidazolium fluorosulfonate can be delocalized on both nitrogens. By the homolytic cleavage of the weak N–S bond (BDE ≈ 70 kcal/mol), this cationic complex undergoes SET process to generate fluorosulfonyl radical (Fig. 1c).

Following this protocol, the authors synthesized a series of highly reactive radical fluorosulfonylating reagents IMSF (2a-2e) for a sequential radical stereoselective fluorosulfonylation.  Both E- and Z-alkenyl sulfonyl fluorides have been readily acheived. This radical fluorosulfonylation protocol has also been extended for hydrofluorosulfonylation and migratory SO2F-difunctionalization of unsaturated hydrocarbon to construct a variety of functionalized sulfonyl fluoride compounds, providing handles for SuFEx reactions. Further studies on this IMSF platform is underway.

Article link:https://www.nature.com/articles/s41467-022-31296-2

Yi Wang

Professor, Nanjing University