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. 2023:3:58.
Epub 2023 Aug 3.

Sulfur fluoride exchange

Joshua A Homer  1 , Long Xu  2   3 , Namitharan Kayambu  4 , Qinheng Zheng  5   6 , Eun Joung Choi  7 , Byeong Moon Kim  7 , K Barry Sharpless  5 , Han Zuilhof  4   8 , Jiajia Dong  2   3   9 , John E Moses  1
Affiliations

Sulfur fluoride exchange

Joshua A Homer et al. Nat Rev Methods Primers. 2023.

Abstract

Sulfur Fluoride Exchange (SuFEx) is a click reaction par excellence that has revolutionized multiple research fields. In this Primer, we delve into the essential elements of SuFEx operation, catalysis, and SuFExable connective hubs. We also explore the cutting-edge applications of SuFEx in drug development, polymer science, and biochemistry. Additionally, we examine the potential limitations and promising prospects for this versatile click reaction.

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Conflict of interest statement

Competing interests Details of patents covering material related to the content of this Primer can be found in the supplementary information.

Figures

Fig 1:
Fig 1:. Sulfur Fluoride Exchange (SuFEx).
A) Important SuFEx hubs. B) SuFEx catalysts. Silicon-mediated and accelerated SuFEx click chemsitries. D) Sequential SuFEx reactions. Part C adapted with permission from ref , Elsevier.
Fig 2.
Fig 2.. Investigation into the SuFEx mechanism.
Potential energy surface (PES) of the reaction of sodium phenolate with sulfonimidoyl fluorides. Part B reprinted with permission from ref , Wiley.
Fig 3.
Fig 3.. Enhancing SuFEx reactivity and practicability.
A) On-water SuFEx. B) Structures and applications of solid fluorosulfonylating agents.
Fig 4.
Fig 4.. SuFEx-based medicinal chemistry.
A) High-throughput SuFEx. B) SuFEx-enabled drug discovery.
Fig 5.
Fig 5.. Unique applications of SuFEx toward function discovery.
A) Covalent inhibitors employing SuFExable groups. B) SuFEx-enabled radiosynthesis. C) Diversity oriented clicking (DOC). Part C adapted with permission from ref , Elsevier.
Fig 6.
Fig 6.. Advances in SuFEx-based polymerizations.
A) Bifluoride-catalyzed polysulfate synthesis. B) Post-polymerization modification. C) Enantiospecific polymerization. D) Chain-growth SuFEx polymerization. PCFF = polymer consistent force field. Part B reprinted from ref , Springer Nature Limited.
Fig 7.
Fig 7.. Bio-compatible SuFEx methods.
A) BioSuFEx. B) Tyrosine-selective modification. C) SuFEx-based bioconjugations. D) Genetically encoded chemical conversion (GECCO). E) Sulfonyl fluoride-based probes. Y = O, NH. Part B reprinted with permission from ref , Wiley.
See this image and copyright information in PMC

References

    1. Kolb HC, Finn MG & Sharpless KB Click chemistry: diverse chemical function from a few good reactions. Angew. Chem. Int. Ed. 40, 2004–2021 (2001).

      This is the original click chemistry manifesto presented by K. Barry Sharpless, outlining the synthesis philosophy and requirements for a reaction to achieve “click” status.

    1. Rostovtsev VV, Green LG, Fokin VV & Sharpless KB A Stepwise Huisgen Cycloaddition Process: Copper(I)-Catalyzed Regioselective “Ligation” of Azides and Terminal Alkynes. Angew. Chem. Int. Ed. 41, 2596–2599 (2002). - PubMed
    1. Tornøe CW, Christensen C & Meldal M Peptidotriazoles on Solid Phase: [1,2,3]-Triazoles by Regiospecific Copper(I)-Catalyzed 1,3-Dipolar Cycloadditions of Terminal Alkynes to Azides. J. Org. Chem. 67, 3057–3064 (2002). - PubMed
    1. Agard NJ, Prescher JA & Bertozzi CR A Strain-Promoted [3 + 2] Azide–Alkyne Cycloaddition for Covalent Modification of Biomolecules in Living Systems. J. Am. Chem. Soc. 126, 15046–15047 (2004). - PubMed

    1. Dong J, Krasnova L, Finn MG & Sharpless KB Sulfur(VI) Fluoride Exchange (SuFEx): Another Good Reaction for Click Chemistry. Angew. Chem. Int. Ed. 53, 9430–9448 (2014).

      This publication represents the re-emergence of SuFEx as a click reaction and describes in detail many of the unique properties of S–F-containing substrates.

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