- Copper-catalyzed three-component reaction of arylhydrazine hydrochloride, DABSO, and NFSI for the synthesis of arenesulfonyl fluorides
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This paper reports a convenient copper-catalyzed three-component conversion of arylhydrazine hydrochlorides to arenesulfonyl fluorides in good yields under mild conditions, using 1,4-diazabicyclo [2.2.2]octane bis(sulfur dioxide) (DABSO) as a sulfonyl source andN-fluorobenzenesulfonimide (NFSI) as a fluorine source based on a radical sulfur dioxide insertion and fluorination strategy. Notably, arylhydrazine hydrochloride is used as a safe precursor of aryl radicals.
- Chen, Qing-Yun,Guo, Yong,Hu, Xiaojun,Liu, Chao,Liu, Yongan,Ma, Xiaoyu,Pan, Qijun,Pang, Wan,Wu, Jingjing
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supporting information
p. 8999 - 9003
(2021/11/04)
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- Metal-Free Visible-Light Synthesis of Arylsulfonyl Fluorides: Scope and Mechanism
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The first metal-free procedure for the synthesis of arylsulfonyl fluorides is reported. Under organo-photoredox conditions, aryl diazonium salts react with a readily available SO2 source (DABSO) to afford the desired product through simple nucleophilic fluorination. The reaction tolerates the presence of both electron-rich and -poor aryls and demonstrated a broad functional group tolerance. To shed the light on the reaction mechanism, several experimental techniques were combined, including fluorescence, NMR, and EPR spectroscopy as well as DFT calculations.
- Louvel, Dan,Chelagha, Aida,Rouillon, Jean,Payard, Pierre-Adrien,Khrouz, Lhoussain,Monnereau, Cyrille,Tlili, Anis
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supporting information
p. 8704 - 8708
(2021/05/17)
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- Arenesulfonyl Fluoride Synthesis via Copper-free Sandmeyer-type Fluorosulfonylation of Arenediazonium Salts
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The limited availability of highly valuable arenesulfonyl fluorides seriously hinders their further application in many research fields including medicinal chemistry and chemical biological, organic synthesis, polymer preparation, etc. We report herein a mild and efficient copper-free Sandmeyer-type fluorosulfonylation reaction of various arenediazonium salts to prepare valuable arenesulfonyl fluorides using K2S2O5 as both a reductant and a practical sulfonyl source in combination with N-fluorobenzenesulfonimide as an effective fluorine source. This methodology provides an attractive route to diverse important arenesulfonyl fluorides given the overall practicality and scope.
- Lin, Qiongzhen,Ma, Zhanhu,Zheng, Changge,Hu, Xiao-Jun,Guo, Yong,Chen, Qing-Yun,Liu, Chao
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supporting information
p. 1107 - 1110
(2020/07/06)
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- Arenesulfonyl Fluoride Synthesis via Copper-Catalyzed Fluorosulfonylation of Arenediazonium Salts
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We report herein a general and practical copper-catalyzed fluorosulfonylation reaction of a wide range of abundant arenediazonium salts to smoothly prepare various arenesulfonyl fluorides using the 1,4-diazabicyclo[2.2.2]octane-bis(sulfur dioxide) adduct as a convenient sulfonyl source in combination with KHF2 as an ideal fluorine source and without the need for additional oxidants. Interestingly, the electronic character of the arene ring in the starting arenediazonium salts has a significant impact on the reaction mechanistic pathway.
- Liu, Yongan,Yu, Donghai,Guo, Yong,Xiao, Ji-Chang,Chen, Qing-Yun,Liu, Chao
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supporting information
p. 2281 - 2286
(2020/03/13)
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- Copper-free Sandmeyer-type Reaction for the Synthesis of Sulfonyl Fluorides
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A copper-free Sandmeyer-type fluorosulfonylation reaction is reported. Utilizing Na2S2O5 and Selectfluor as the sulfur dioxide and fluorine sources, respectively, aryldiazonium salts were transformed into sulfonyl fluorides. The one-pot direct synthesis of sulfonyl fluorides from aromatic amines was also realized via in situ diazotization. The practicality of this method was demonstrated by the broad functional group tolerance, gram-scale synthesis, and late-stage fluorosulfonylation of natural products and pharmaceuticals.
- Zhong, Tao,Pang, Meng-Ke,Chen, Zhi-Da,Zhang, Bin,Weng, Jiang,Lu, Gui
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supporting information
p. 3072 - 3078
(2020/04/10)
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- SuFEx-enabled, agnostic discovery of covalent inhibitors of human neutrophil elastase
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Sulfur fluoride exchange (SuFEx) has emerged as the new generation of click chemistry. We report here a SuFEx-enabled, agnostic approach for the discovery and optimization of covalent inhibitors of human neutrophil elastase (hNE). Evaluation of our ever-growing collection of SuFExable compounds toward various biological assays unexpectedly revealed a selective and covalent hNE inhibitor: benzene-1,2-disulfonyl fluoride. Synthetic derivatization of the initial hit led to a more potent agent, 2-(fluorosulfonyl)phenyl fluorosulfate with IC50 0.24 μM and greater than 833-fold selectivity over the homologous neutrophil serine protease, cathepsin G. The optimized, yet simple benzenoid probe only modified active hNE and not its denatured form.
- Zheng, Qinheng,Woehl, Jordan L.,Kitamura, Seiya,Santos-Martins, Diogo,Smedley, Christopher J.,Li, Gencheng,Forli, Stefano,Moses, John E.,Wolan, Dennis W.,Barry Sharpless
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p. 18808 - 18814
(2019/09/30)
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- A study of the reactivity of S(VI)-F containing warheads with nucleophilic amino-acid side chains under physiological conditions
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Sulfonyl fluorides (SFs) have recently emerged as a promising warhead for the targeted covalent modification of proteins. Despite numerous examples of the successful deployment of SFs as covalent probe compounds, a detailed exploration of the factors influencing the stability and reactivity of SFs has not yet appeared. In this work we present an extensive study on the influence of steric and electronic factors on the reactivity and stability of the SF and related SVI-F groups. While SFs react rapidly with N-acetylcysteine, the resulting adducts were found to be unstable, rendering SFs inappropriate for the durable covalent inhibition of cysteine residues. In contrast, SFs afforded stable adducts with both N-acetyltyrosine and N-acetyllysine; furthermore, we show that the reactivity of arylsulfonyl fluorides towards these nucleophilic amino acids can be predictably modulated by adjusting the electronic properties of the warhead. These trends were largely conserved when the covalent reaction occurred within a protein binding pocket. We have also obtained a crystal structure depicting covalent modification of the catalytic lysine of a tyrosine kinase (FGFR1) by the ATP analog 5′-O-3-((fluorosulfonyl)benzoyl)adenosine (m-FSBA). Highly reactive warheads were demonstrated to be unstable with respect to hydrolysis in buffered aqueous solutions, indicating that warhead reactivity must be carefully tuned to provide optimal rates of protein modification. Our results demonstrate that the reactivity of SFs complements that of more commonly studied acrylamides, and we hope that this work spurs the rational design of novel SF-containing covalent probe compounds and inhibitors, particularly in cases where a suitably positioned cysteine residue is not present.
- Mukherjee,Debreczeni,Breed,Tentarelli,Aquila,Dowling,Whitty,Grimster
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supporting information
p. 9685 - 9695
(2017/11/30)
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- Pd-Catalyzed Conversion of Aryl Iodides to Sulfonyl Fluorides Using SO2 Surrogate DABSO and Selectfluor
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A one-pot Pd-catalyzed conversion of aryl iodide to aryl sulfonyl fluorides using DABSO and Selectfluor has been developed generating aryl sulfonyl fluorides in good to excellent yields. The reaction results in the generation of electronically and sterically diverse sulfonyl fluorides. Additionally, sulfonyl fluorides can be converted to aryl sulfonamides and sulfonic esters using Cs2CO3 under mild conditions.
- Tribby, Ariana L.,Rodríguez, Ismeraí,Shariffudin, Shamira,Ball, Nicholas D.
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p. 2294 - 2299
(2017/02/26)
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- KINETIC INVESTIGATION OF THE S-FLUORINATION OF ARENESULFINATES WITH PERCHLORYL FLUORIDE
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The effect of substituents and solvents on the kinetics of S-fluorination of sodium arenesulfinates with perchloryl fluoride was investigated.Alternative fluorination mechanisms were examined, and it was found that the mechanism is SN2 substitution at the fluorine atom.
- Vigalok, I. V.,Petrova, G. G.,Lukashina, S. G.,Vigalok, A. A.,Levin, Ya. A.
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p. 1239 - 1243
(2007/10/02)
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