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NFSI and Its Analogs Electrophilic Fluorination for Preparing Alkyl Fluorides

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Fluorination

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

Introduction

Electrophilic fluorination provides one of the most powerful and efficient methods for the synthesis of organofluorine compounds. Although molecular fluorine and oxygen-fluorine compounds can be used in the electrophilic fluorination reactions, these reagents are poorly selective and difficult to handle because of their high toxicity and explosive nature. From the late 1980s, various N-fluoro compounds, which have proven to be the most economical, stable, mild, and safe electrophilic fluorinating agents, have been developed and widely used in organic synthesis [1]. Two classes of N-fluoro reagents are known: neutral N-F reagents (R2N-F) and quaternary ammonium N-F reagents (R3NF+X−). Here we will focus on typical neutral electrophilic N-F reagents, including N-fluoro-benzenesulfonimide (NFSI), N-fluoro-o-benzenedisulfonimide (NFOBS), N-fluoro-camphorsultam (N-F-sultam), and N-fluoro-binaphthyldisulfonimide (N-F-BINAS) (Fig. 1). These reagents are a series of readily...

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References

  1. Lal GS, Pez GP, Syvret RG (1996) Electrophilic NF fluorinating agents. Chem Rev 96:1737–1755

    Article  CAS  Google Scholar 

  2. Differding E, Ofner H (1991) N-Fluorobenzenesulfonimide: A Practical reagent for electrophilic fluorinations. Synlett 187–189

    Google Scholar 

  3. Davis FA, Han W (1991) N-Fluoro-o-benzenedisulfonimide: A useful new fluorinating reagent. Tetrahedron Lett 32:1631–1634

    Article  CAS  Google Scholar 

  4. Verniest G, Van Hende E, Surmont R, De Kimpe N (2006) Direct electrophilic α-fluorination of imines: Efficient synthesis of mono- and difluoroimines. Org Lett 8:4767–4770

    Google Scholar 

  5. Differding E, Lang RW (1988) New fluorination reagents - I. The first enantioselective fluorination reaction. Tetrahedron Lett 29: 6087–6090

    Google Scholar 

  6. Davis FA, Zhou P, Murphy CK (1993) Asymmetric fluorination of enloates with N-fluoro 2,10-(3,3-dichlorocamphorsultam). Tetrahedron Lett 34: 3971–3974

    Article  CAS  Google Scholar 

  7. Zhu CL, Maeno M, Zhang FG, Shigehiro T, Kagawa T, Kawada K, Shitaba N, Ma JA, Cahard D (2013) Chiral N-fluorodibenzenesulfonimide analogues for enantioselective electrophilic fluorination and oxidative fluorination. Eur J Org Chem 6501–6505

    Google Scholar 

  8. Davis FA, Han W (1992) Diastereoselective fluorination of chiral imide enloates using N-fluoro-o-benzenedisulfonimide (NFOBS). Tetrahedron Lett 33: 1153–1156

    Article  CAS  Google Scholar 

  9. Davis FA, Kasu PVN (1998) Asymmetric synthesis of α-fluoro ketones using α-fluoro oxazolidinone carboximudes. Tetrahedron Lett 39: 6135–6138

    Article  CAS  Google Scholar 

  10. Davis FA, Kasu PVN, Sundarababu G, Qi H (1997) Nonrecemic α-fluoro aldehydes: Asymmetric synthesis of 4-deoxy-4-fluoro-D-arabinopyranose. J Org Chem 62:7546–7547

    Article  CAS  Google Scholar 

  11. Enders D, Potthoff M, Raabe G, Runsink J (1997) α-Fluoroketones by electrophilic fluorination of α-silylketone enolates with N-fluorobenzosulfonimide. Angew Chem Int Ed 36: 2362–2364

    Article  CAS  Google Scholar 

  12. Hintermann L, Togni A (2000) Catalytic enantioselective fluorination of β-ketoesters. Angew Chem Int Ed 39: 4359–4362

    Article  CAS  Google Scholar 

  13. Kim DY, Park EJ (2002) Catalytic enantioselective fluorination of α-keto esters by phase-transfer catalysis using chiral quaternary ammonium salts. Org Lett 4:545–547

    Google Scholar 

  14. Tanzer EM, Schweizer WB, Ebert MO, Gilmour R (2012) Designing fluorinated cinchona alkaloids for enantioselective catalysis: Controlling internal rotation by a fluorine-ammonium ion gauche effect (φNCCF). Chem Eur J 18:2006–2013

    Article  CAS  Google Scholar 

  15. Wang X, Lan Q, Shirakawa S, Maruoka K (2010) Chiral bifunctional phase transfer catalysts for asymmetric fluorination of β-keto esters. Chem Comm 46:321–323

    Article  CAS  Google Scholar 

  16. You Y, Zhang L, Luo S (2017) Reagent-controlled enantioselectivity switch for the asymmetric fluorination of β-ketocarbonyls by chiral primary amine catalysis. Chem Sci 8:621–626

    Google Scholar 

  17. Hamashima Y, Yagi K, Takano H, Tamas L, Sodeoka M (2002) An efficient enantioselective fluorination of various β-ketoesters catalyzed by chiral palladium complexes. J Am Chem Soc 124:14530–14531

    Article  CAS  Google Scholar 

  18. Ma JA, Cahard D (2004) Copper(II) triflate-bis(oxazoline)-catalysed enantioselective electrophilic fluorination of β-ketoesters. Tetrahedron: Asymmetry 15:1007–1011

    Article  CAS  Google Scholar 

  19. Shibata N, Kohno J, Takai K, Ishimaru T, Nakamura S, Toru T, Kanemasa S (2005) Highly enantioselective catalytic fluorination and chlorination reactions of carbonyl compounds capable of two-point binding. Angew Chem Int Ed 44: 4204–4207

    Article  CAS  Google Scholar 

  20. Althaus M, Becker C, Togni A, Mezzetti A (2007) Ruthenium-catalyzed asymmetric electrophilic fluorination of 1,3-dicarbonyl compounds. Organometallics 26: 5902–5911

    Article  CAS  Google Scholar 

  21. Reddy DS, Shibata N, Nagai J. Nakamura S, Toru T, Kanemasa S (2008) Desymmetrization-like catalytic enantioselective fluorination of malonates and its application to pharmaceutically attractive molecules. Angew Chem Int Ed 47: 164–168

    Article  CAS  Google Scholar 

  22. Hamashima Y, Suzuki T, Shimura Y, Shimizu T, Umebayashi N, Tamura T, Sasamoto N, Sodeoka M (2005) An efficient catalytic enantioselective fluorination of β-ketophosphonates using chiral palladium complexes. Tetrahedron Lett 46: 1447–1450

    Google Scholar 

  23. Kang K, Cho MJ, Kim SM, Kim DY (2007) Asymmetric electrophilic fluorination of α-cyanoalkylphosphonates catalyzed by chiral palladium complexes. Synlett 1135–1138

    Google Scholar 

  24. Moriya KI, Hamashima Y, Sodeoka M (2007) Pd(II)-catalyzed asymmetric fluorination of α-aryl-α-cyanophosphonates with the aid of 2,6-lutidine. Synlett 1139–1142

    Google Scholar 

  25. Suzuki S, Kitamura Y, Lectard S, Hamashima Y, Sodeoka M (2012) Catalytic asymmetric mono-fluorination of α-keto esters: Synthesis of optically active β-fluoro-α-hydroxy and β-fluoro-α-amino acid derivatives. Angew Chem Int Ed 51: 4581–4585

    Article  CAS  Google Scholar 

  26. Suzuki S, Hamashima Y, Sodeoka M (2007) Asymmetric fluorination of α-aryl acetic acid derivatives with the catalytic system NiCl2–Binap/R3SiOTf/2,6-lutidine. Angew Chem Int Ed 46: 5435–5439

    Article  CAS  Google Scholar 

  27. Zhu W, Hu X, Wang F, Yang X, Wu X (2015) A convenient preparation of fluorinating reagent F-TEDA bearing bisphenylsulfonylimide counterion and its fluorination to oxindoles. Chin J Chem 33:220–224

    Article  CAS  Google Scholar 

  28. Hamashima Y, Suzuki T, Takano H, Shimura Y, Sodeoka M (2005) Catalytic enantioselective fluorination of oxindoles. J Am Chem Soc 127:10164–10165

    Article  CAS  Google Scholar 

  29. Deng QH, Wadepohl H, Gade LH (2011) The synthesis of a new class of chiral pincer ligands and their applications in enantioselective catalytic fluorinations and the Nozaki–Hiyama–Kishi reaction. Chem Eur J 17:14922–14928

    Article  Google Scholar 

  30. Li J, Cai YF, Chen WL, Liu XH, Lin LL, Feng XM (2012) Highly enantioselective fluorination of unprotected 3-substituted oxindoles: One-step synthesis of BMS 204352 (MaxiPost). J Org Chem 77: 9148–9155

    Article  CAS  Google Scholar 

  31. Meng WT, Zheng Y, Nie J, Xiong HY, Ma JA (2013) Organocatalytic asymmetric one-pot sequential conjugate addition/dearomative fluorination: Synthesis of chiral fluorinated isoxazol-5(4H)-ones. J Org Chem 78:559–567

    Article  CAS  Google Scholar 

  32. Zhang H, Wang B, Cui L, Bao X, Qu J, Song Y (2015) Organocatalytic asymmetric fluorination of 4-substituted isoxazolinones. Eur J Org Chem 2143–2147

    Google Scholar 

  33. Paull DH, Scerba MT, Alden-Danforth E, Widger LR, Lectka T (2008) Catalytic, asymmetric α-fluorination of acid chlorides: Dual metal-ketene enolate activation. J Am Chem Soc 130: 17260–17261

    Article  CAS  Google Scholar 

  34. Erb J, Paull DH, Dudding T, Belding L, Lectka T (2013) From bifunctional to trifunctional (tricomponent nucleophile-transition metal-Lewis acid) catalysis: The catalytic, enantioselective α-fluorination of acid chlorides. J Am Chem Soc 133: 7536–7546

    Google Scholar 

  35. Marigo M, Fielenbach D, Braunton A, Kjæsgarrd A, Jørgensen KA (2005) Enantioselective formation of stereogenic carbon-fluorine centers by a simple catalytic method. Angew Chem Int Ed 44: 3703–3706

    Article  CAS  Google Scholar 

  36. Franzén J, Marigo M, Fielenbach D, Wabnitz TC, Kjæsgarrd A, Jørgensen KA (2005) A general organocatalyst for direct α-functionalization of aldehydes: Stereoselective C-C, C-N, C-F, C-Br, and C-S bond-forming reactions. Scope and mechanistic insights. J Am Chem Soc 127: 18296–18304

    Article  Google Scholar 

  37. Steiner DD, Mase N, Barbas III CF (2005) Direct asymmetric α-fluorination of aldehydes. Angew Chem Int Ed 44: 3706–3710

    Article  CAS  Google Scholar 

  38. Besson TD, MacMillan DWC (2005) Enantioselective organocatalytic α-fluorination of aldehydes. J Am Chem Soc 127: 8826–8828

    Article  Google Scholar 

  39. Li F, Wu Z, Wang J (2015) Oxidative enantioselective α-fluorination of aliphatic aldehydes enabled by N-heterocyclic carbene catalysis. Angew Chem Int Ed 54: 656–659

    CAS  Google Scholar 

  40. Zhao YM, Cheung MS, Lin Z, Sun J (2012) Enantioselective synthesis of β,γ-unsaturated α-fluoroesters catalyzed by N-heterocyclic carbenes. Angew Chem Int Ed 51: 10359–10363

    Article  CAS  Google Scholar 

  41. Zhu Q, Ji D, Liang T, Wang X, Xu Y (2015) Efficient palladium-catalyzed C-H fluorination of C(sp3)-H bonds: Synthesis of β‑fluorinated carboxylic acids. Org Lett 17: 3798-3801.

    Google Scholar 

  42. 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

    Google Scholar 

  43. Meanwell M, Nodwell MB, Martin RE, Britton R (2016) A convenient late-stage fluorination of pyridylic C-H bonds with N-fluorobenzenesulfonimide. Angew Chem Int Ed 55: 13244–13248

    Article  CAS  Google Scholar 

  44. Ishimaru T, Shibata N, Horikawa T, Yasuda N, Nakamura S, Toru T, Shiro M (2008) Cinchona alkaloid catalyzed enantioselective fluorination of allyl silanes, silyl enol ethers, and oxindoles. Angew Chem Int Ed 47: 4157–4161

    Article  CAS  Google Scholar 

  45. Qiu S, Xu T, Zhou J, Guo Y, Liu G (2010) Palladium-catalyzed intermolecular aminofluorination of styrenes. J Am Chem Soc 132:2856–2857

    Article  CAS  Google Scholar 

  46. Xu T, Qiu S, Liu G (2011) Palladium-catalyzed intramolecular aminofluorination of styrenes. Chin J Chem 29:2785–2790

    Article  CAS  Google Scholar 

  47. Zhang H, Song Y, Zhao J, Zhang J, Zhang Q (2014) Regioselective radical aminofluorination of styrenes. Angew Chem Int Ed 53: 11079–11083

    Article  CAS  Google Scholar 

  48. Wang L, Meng W, Zhu CL, Zheng Y, Nie J, Ma JA (2011) The long-arm effect: Influence of axially chiral phosphoramidite ligands on the diastereo- and enantioselectivity of the tandem 1,4-addition/fluorination. Angew Chem Int Ed 50: 9442–9446

    Article  CAS  Google Scholar 

  49. Miró J, del Pozo C, Toste FD, Fustero S (2016) Enantioselective palladium-catalyzed oxidative β,β-fluoroarylation of α,β-unsaturated carbonyl derivatives. Angew Chem Int Ed 50: 9045-9049

    Article  Google Scholar 

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Authors and Affiliations

  1. Tianjin Key Laboratory of Molecular Optoelectronic Science, Department of Chemistry, School of Science, Tianjin University, Tianjin, 300072, People’s Republic of China

    Guangwei Wang & Jun-An Ma

Authors
  1. Guangwei Wang
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  2. Jun-An Ma
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Correspondence to Jun-An Ma .

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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

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Wang, G., Ma, JA. (2018). NFSI and Its Analogs Electrophilic 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_6-1

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  • DOI: https://doi.org/10.1007/978-981-10-1855-8_6-1

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  • Print ISBN: 978-981-10-1855-8

  • Online ISBN: 978-981-10-1855-8

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