Skip to main content
SpringerLink
Log in

NFSI Radical Fluorination for Preparing Alkyl Fluorides

  • Living reference work entry
  • First Online:
Fluorination

Part of the book series: Synthetic Organofluorine Chemistry ((SYOC))

Introduction

While nucleophilic and electrophilic fluorination have made great progress in recent decades [1], the direct fluorination of sp3-carbon centered radical provides a powerful method for the synthesis of alkyl fluorides. In early times, the hazardous, uncontrollable fluorine gas (F2) [2] and hypofluorite (ROF) [3] or costly xenon difluoride (XeF2) [4] were generally employed as the atomic fluorine reagents that restricted the development of this area. Along with the extensive use of stable and easily handling fluorinating agents, such as N-fluorobenzenesulfonimide (NFSI), SelectFluor, and N-fluoropyridinium salts (NFPY), the revival of radical fluorination is aroused [5, 6].

The DFT calculation of N-F bonds in NFSI, SelectFluor, and NFPY was studied by Sammis and coworkers [7]. The BDE (bond dissociation energy) of N-F bond in NFSI (ca. 63 kcal/mol) is similar to that in SelectFluor (ca. 61–62 kcal/mol); the BDE of N-F bond in NFPY (ca. 75–76 kcal/mol) is slightly larger....

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  1. Kirk KL (2008) Fluorination in medicinal chemistry: methods, strategies, and recent developments. Org Process Res Dev 12: 305-321

    Article  CAS  Google Scholar 

  2. Wang CM, Mallouk TE (1990) A new photochemical method for selective fluorination of organic molecules. J Am Chem Soc 112: 2016-2018

    Article  CAS  Google Scholar 

  3. Rozen S, Hebel D (1990) Acyl hypofluorites. A new class of organic compounds. J Org Chem 55: 2621-2623

    Article  CAS  Google Scholar 

  4. Patrick TB, Khazaeli S, Nadji S, Hering-Smith K, Reif D (1993) Mechanistic studies of fluorodecarboxylation with xenon difluoride. J Org Chem 58: 705-708

    Article  CAS  Google Scholar 

  5. Yan H, Zhu C (2017) Recent advances in radical-mediated fluorination through C-H and C-C bond cleavage. Sci China Chem 60: 214-222

    Google Scholar 

  6. Chatalova-Sazepin C, Hemelaere R, Paquin J-F, Sammis GM (2015) Recent advances in radical fluorination. Synthesis 47: 2554-2569

    Article  CAS  Google Scholar 

  7. Rueda-Becerril M, Sazepin CC, Leung JCT, Okbinoglu T, Kennepohl P, Paquin J-F, Sammis GM (2012) Fluorine transfer to alkyl radicals. J Am Chem Soc 134: 4026-4029

    Article  CAS  Google Scholar 

  8. Nyffeler PT, Durón SG, Burkart MD, Vincent SP, Wong CH (2005) Selectfluor: mechanistic insight and applications. Angew Chem Int Ed 44: 192-212

    Article  CAS  Google Scholar 

  9. DifferdingE, Ofner H(1991) N-fluorobenzenesulfonimide: a practical reagent for electrophilic fluorinations. Synlett 1991: 187-189

    Article  Google Scholar 

  10. Yin F, Wang Z, Li Z, Li C (2012) Silver-catalyzed decarboxylative fluorination of aliphatic carboxylic acids in aqueous solution. J Am Chem Soc 134: 10401-10404

    Article  CAS  Google Scholar 

  11. Leung JCT, Sammis GM (2015) Radical decarboxylative fluorination of aryloxyacetic acids using N-Fluorobenzenesulfonimide and a photosensitizer. Eur J Org Chem 2015: 2197-2204

    Article  CAS  Google Scholar 

  12. Liu W, Huang X, Cheng M-J, Nielsen RJ, Goddard III WA, Groves JT (2012) Oxidative aliphatic C-H fluorination with fluoride ion catalyzed by a manganese porphyrin. Science 337: 1322-1325

    Article  CAS  Google Scholar 

  13. Bloom S, Pitts CR, Miller DC, Haselton N, Holl MG, Urheim E, Lectka T (2012) A polycomponent metal-catalyzed aliphatic, allylic, and benzylic fluorination. Angew Chem Int Ed 51: 10580-10583

    Article  CAS  Google Scholar 

  14. Halperin SD, Fan H, Chang S, Martin RE, Britton R (2014) A convenient photocatalytic fluorination of unactivated C-H bonds. Angew Chem Int Ed 53: 4690 –4693

    Article  CAS  Google Scholar 

  15. Halperin SD, Kwon D, Holmes M, Regalado EL, Campeau L-C, DiRocco DA, Britton R (2015) Development of a direct photocatalytic C−H fluorination for the preparative synthesis of odanacatib. Org Lett 17: 5200-5203

    Article  CAS  Google Scholar 

  16. Pitts CR, Ling B, Snyder JA, Bragg AE, Lectka T (2016) Aminofluorination of cyclopropanes: a multifold approach through a common, catalytically generated intermediate. J Am Chem Soc 138: 6598-6609

    Article  CAS  Google Scholar 

  17. Purser S, Moore PR, Swallow S, Gouverneur V (2008) Fluorine in medicinal chemistry. Chem Soc Rev 37: 320-330

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, 199 Ren-Ai Road, 215123, Suzhou, Jiangsu, China

    Hong Yan & Chen Zhu

Authors
  1. Hong Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chen Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chen Zhu .

Editor information

Editors and Affiliations

  1. Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China

    Jinbo Hu

  2. R&D Center, Zhejiang Jiuzhou Pharmaceutical Co., Ltd, Taizhou, Zhejiang, China

    Teruo Umemoto

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this entry

Cite this entry

Yan, H., Zhu, C. (2018). NFSI Radical Fluorination for Preparing Alkyl Fluorides. In: Hu, J., Umemoto, T. (eds) Fluorination. Synthetic Organofluorine Chemistry. Springer, Singapore. https://doi.org/10.1007/978-981-10-1855-8_1-1

Download citation

  • DOI: https://doi.org/10.1007/978-981-10-1855-8_1-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-10-1855-8

  • Online ISBN: 978-981-10-1855-8

  • eBook Packages: Springer Reference Chemistry and Mat. ScienceReference Module Physical and Materials ScienceReference Module Chemistry, Materials and Physics

Publish with us

Policies and ethics

Search

Navigation