Recent Advances in Synthetic Methodology of Sulfur(VI) Fluoride Exchange Click Reactions

doi:10.6023/cjoc202512025

Abstract

Sulfur(VI) fluoride exchange (SuFEx) is new generation of click chemistry developed by Sharpless and co-workers. Over the past decade, SuFEx has found broad applications in synthetic chemistry, materials science, chemical biology, and drug discovery. Chemists have prepared a variety of SuFEx linkers, which can efficiently undergo SuFEx reactions with different nucleophiles to afford a diverse of highly valued sulfur-containing compounds such as sulfonamides, sulfonates and so on. Compared to S(VI)—Cl bond, S(VI)—F bond has higher bond-dissociation energy and chemical stability. Consequently, SuFEx reactions usually require specific reaction conditions and catalysts. This review summarizes recent advances in SuFEx reactions involving different linkers, with an emphasis on their methodological development.

Key words: sulfur (VI) fluoride exchange, click reaction, SuFEx linker, sulfur-containing compounds

Cite this article

Dilfiragul Mangnahun, Qichao Zhang, Fang Zhang, Lin He, Zhihua Cai, Guangfen Du. Recent Advances in Synthetic Methodology of Sulfur(VI) Fluoride Exchange Click Reactions[J]. Chinese Journal of Organic Chemistry, 2026, 46(8): 2988-3011.

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Fig. & Tab. 55

Scheme 1. Click reaction and SuFEx linkers

Scheme 2. (A) Reaction of SO2F2 with phenols; (B) Reaction of SO2F2 with heterocyclic phenols

Scheme 3. Accelerated SuFEx reaction

Scheme 4. Reaction of SO2F2 with amines

Scheme 5. Three-component reaction involving SO2F2

Scheme 6. Reaction of SO2F2 with guanidine hydrochlorides

Scheme 7. Synthesis of SuFEx-IT and their reactions with phenols and amines

Scheme 8. Synthesis of AISF and its reactions with phenols and cyclic secondary amines

Scheme 9. SuFEx reactions involving BTSF and BDSF

Scheme 10. Synthesis and applications of fluorosulfonyl azides

Scheme 11. Reaction involving novel sulfur(VI) fluorides SIFs

Scheme 12. Reaction of sulfonyl fluorides with oxygen nucleophiles

Scheme 13. ChB-activated SuFEx reaction

Scheme 14. Accelarated SuFEx reaction

Scheme 15. Rreaction of aryl fluorosulfates with sugar or amino acid

Scheme 16. NHC-catalyzed SuFEx reaction

Scheme 17. Bifluoride salt catalyzed SuFEx polymerization

Scheme 18. SuFEx reaction of sulfonyl fluorides with amines

Scheme 19. Synthesis of sulfonamides via SuFEx reaction

Scheme 20. HOBt-catalyzed SuFEx reaction of sulfonyl fluorides with fluorosulfates and amines

Scheme 21. NHC-catalyzed SuFEx reaction of amines

Scheme 22. SuFEx reaction involving gaseous CF3SO2F

Scheme 23. Synthesis of sulfonamides under NMI mediation

Scheme 24. Friedel-Crafts cyclizations involving substrates with SuFEx reactivity

Scheme 25. SuFEx reaction of SOF4 with amines

Scheme 26. (A) Synthesis of sulfoximine fluorides; (B) SuFEx reaction of sulfoximine difluorides with silyl ethers; (C) Selective SuFEx reactions of SO2F2 and SOF4

Scheme 27. SuFEx reactions involving sulfoximine difluorides

Scheme 28. SuFEx reactions of sulfonimidoyl derivatives with oxygen nucleophiles

Scheme 29. C-SuFEx reaction of sulfilimine monofluorides with alkynyl silyl ethers

Scheme 30. C-SuFEx reaction of sulfilimine monofluorides with acyclic alkenes

Scheme 31. C-SuFEx reactions of fluorinated sulfoximines with allylsilanes

Scheme 32. TMSOTf-catalyzed C-SuFEx reaction

Scheme 33. Applications of fluorinated sulfonimidates in the synthesis of polymeric compound

Scheme 34. Highly enantioenriched sulfoximines prepared from bench-stable N-Boc-sulfinylamine salts

Scheme 35. Optically active sulfoximine derivatives synthesized from chiral S(Ⅵ)-t-Bu

Scheme 36. Asymmetric 3D sulfur-fluoride exchange (3D-SuFEx)

Scheme 37. Synthesis and applications of chiral SuFEx linkers SIFs

Scheme 38. NaHF2 promoted asymmetric F/Cl exchange reaction at the S(VI) center

Scheme 39. Kilogram-scale synthesis of ESF via an aqueous- phase reaction

Scheme 40. Heck reaction involving ESF

Scheme 41. SuFEx reaction of β-aryl vinylsulfonyl fluorides with amines

Scheme 42. SuFEx reaction of β-aryl vinylsulfonyl fluorides with ketones

Scheme 43. Efficient synthesis of sultones via SuFEx reaction

Scheme 44. Synthesis and applications of BESF

Scheme 45. Applications of ESF in the synthesis of SuFExable substrates

Scheme 46. SuFEx linkers prepared from BESF

Scheme 47. Synthesis of BDF and its application in preparing SuFEx-active substrate

Scheme 48. Construction of triphenylbenzenes via β-aryl vinylsulfonyl fluorides

Scheme 49. Construction of cyclohexenes and cyclopentenes via tandem reaction of β-aryl vinylsulfonyl fluorides

Scheme 50. Cycloaddition of β-aryl vinylsulfonyl fluorides with o-hydroxy azomethine ylides

Scheme 51. Synthesis of α-arylpyrrolidines with β-aryl vinylsulfonyl fluorides

Scheme 52. SuFEx reaction of β-aryl vinylsulfonyl fluorides with oxindoles and benzofuranones

Scheme 53. Silica-promoted SuFEx cyclization

Scheme 54. Synthesis of SASF and its reactions

Scheme 55. Synthesis of novel clickable thiazoles using SASF

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