N-Fluorobenzenesulfonimide

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

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