N-Fluorobenzenesulfonimide

Vincent Bizet received his Master degree in 2009 from the University of Caen, France under the supervision of Professor Jacques Rouden and Professor Marie-Claire Lasne. He is currently working towards his PhD at the INSA of Rouen, France under the super­vision of Dr. Dominique Cahard (CNRS Research Director). His ­research interest focusses on the asymmetric synthesis of fluorinated compounds and on catalysis by transition metals.

Introduction

N-Fluorobenzenesulfonimide (NFSI) is a colorless crystalline powder with a melting point of 114–116 °C. One of the most convenient routes to prepare NFSI in high yield is the fluorination with 10% v/v F₂ in N₂ of N-(phenyl­sulfonyl)benzenesulfonamide in MeCN at –40 °C (Scheme [1]).[ ¹ ] NFSI can also be prepared from the corresponding sodium salt.[ ² ] NFSI has been widely used as an electrophilic fluorinating agent most particularly in the field of asymmetric electrophilic fluorination.[ ³ ] But NFSI is more than an electrophilic fluorinating agent: It is also a strong oxidant for organometallic intermediates to promote reductive elimination through high-oxidation-state transition metals, an amination reagent and even a phenylsulfonyl group transfer reagent.

Scheme 1 Synthesis of N-fluorobenzenesulfonimide (NFSI)

Abstracts

NFSI as Fluorinating Reagent: (A) Shibata and co-workers reported the enantioselective synthesis of 3′-fluorothalidomide through an electrophilic fluorination using a combination of cinchona alkaloid and NFSI. The appropriate choice of additives allowed enantiodivergent fluorination using a single alkaloid; indeed, TMEDA as ligand provided the S-enantiomer whereas bipy–Cu(acac)2 gave the R-enantiomer. Pure enantiomers were obtained after deprotection and oxidation.[ 4 ] In the prospect of the synthesis of radiopharmaceuticals, such as 18F-fluorothalidomide, for positron emission tomography (PET) analysis, [18F]NFSI has been developed.[ 5 ]
(B) Mazet, Alexakis and co-workers have developed a sequential iridium-catalyzed redox isomerization–organocatalytic fluorination. The intermediate aldehyde, which was the result of the redox iso­merization of the starting primary allylic alcohol, was submitted to the electrophilic fluorination by means of NFSI through enamine catalysis with 20 mol% of a proline derivative. A quench by NaBH4 produced the fluoroalcohol that featured two stereogenic centers in an overall 49% yield with 99% ee for the main syn-diastereoisomer.[ 6 ]
NFSI as Oxidizing Reagent: (C) NFSI has been used as a versatile oxidant in reactions that involve a PdII–PdIV catalytic cycle.[ 7 ] Michael and co-workers described the palladium-catalyzed diamination, carboamination and alkoxyamination of unactivated alkenes using NFSI as an oxidant. The ­oxidative addition of NFSI allowed the formation of a PdIV intermediate; then reductive elimination led to the diamination product A.[ 8 ] The PdIV intermediate could also react with nucleophilic arenes to form the carboamination product B through C–H activation followed by reductive elimination.[ 9 ] When the reaction was performed in alcoholic solvents, the solvolysis of the PdIV intermediate led to the alkoxyamination 5-exo product C or through neighboring group participation to the 6-endo product D depending on solvent polarity.[ 10 ]
NFSI as Amination Reagent: (D) NFSI has also been used to realize the selective amination of various compounds. Zhang and co-workers described the amide-­directed palladium-catalyzed selective aromatic C–H amination of anilides with NFSI in good yields.[ 11 ] In addition, it was demonstrated that NFSI is the decisive reagent for the oxidative amination of C(sp3)–H bonds at benzylic positions under palladium[12] [13] or copper catalysis.[ 14 ]
(E) Liu and co-workers described an intermolecular Pd-catalyzed oxidative aminofluorination of vinyl arenes with NFSI in the presence of bathocuproine. NFSI functioned not only as an amination agent but also as a fluorination and an oxidizing reagent. The reaction affords vicinal fluoroamine products with very high regio­selectivity.[ 15 ]
NFSI as Phenylsulfonyl Transfer Reagent: (F) The reaction of the purine C-8 carbanion of a protected 5′-noraristeromycin derivative with NFSI failed to give the expected 8-fluoroderivatives but gave the 8-phenylsulfonyl-5′-noraristeromycin instead. This phenylsulfonyl transfer proceeds via a single electron transfer.[ 16 ]

• References

• 1a Differding E, Ofner H. Synlett 1991; 187
• 1b Differding E. US Patent 5,254,732, 1993
• 2 Wagner WJ, Shia GA, Poss AJ. Intl. Patent WO 94/08955, 1994
• 3a Ma J.-A, Cahard D. Chem. Rev. 2008; 108: PR1-PR43
• 3b Baudoux J, Cahard D. Org. React. John Wiley & Sons; Hoboken: 2007: 347
• 4 Yamamoto T, Suzuki Y, Ito E, Tokunaga E, Shibata N. Org. Lett. 2011; 13: 470
• 5 Teare H, Robins EG, Arstad E, Luthra SK, Gouverneur V. Chem. Commun. 2007; 2330
• 6 Quintard A, Alexakis A, Mazet C. Angew. Chem. Int. Ed. 2011; 50: 2354
• 7a Wang X, Leow D, Yu J.-Q. J. Am. Chem. Soc. 2011; 133: 13864
• 7b Ball ND, Gary JB, Ye Y, Sanford MS. J. Am. Chem. Soc. 2011; 133: 7577
• 7c Xu T, Qiu S, Liu G. J. Organomet. Chem. 2011; 696: 46
• 8 Sibbald PA, Michael FE. Org. Lett. 2009; 11: 1147
• 9a Rosewall CF, Sibbald PA, Liskin DV, Michael FE. J. Am. Chem. Soc. 2009; 131: 9488
• 9b Sibbald PA, Rosewall CF, Swartz RD, Michael FE. J. Am. Chem. Soc. 2009; 131: 15945
• 10 Liskin DV, Sibbald PA, Rosewall CF, Michael FE. J. Org. Chem. 2010; 75: 6294
• 11 Sun K, Li Y, Xiong T, Zhang J, Zhang Q. J. Am. Chem. Soc. 2011; 133: 1694
• 12 Iglesias Á, Álvarez R, de Lera ÁR, Muñiz K. Angew. Chem. Int. Ed. 2012; 51: 2225
• 13 Xiong T, Li Y, Lv Y, Zhang Q. Chem. Commun. 2010; 46: 6831
• 14 Ni Z, Zhang Q, Xiong T, Zheng Y, Li Y, Zhang H, Zhang J, Liu Q. Angew. Chem. Int. Ed. 2012; 51: 1244
• 15 Qiu S, Xu T, Zhou J, Guo Y, Liu G. J. Am. Chem. Soc. 2010; 132: 2856
• 16 Roy A, Schneller SW. Org. Lett. 2005; 7: 3889