N-fluorobenzenesulfonimide Research Articles

Fluorination of 2H-Indazoles Using N-Fluorobenzenesulfonimide.

An efficient, simple, and metal-free fluorination of 2H-indazoles has been developed using N-fluorobenzenesulfonimide (NFSI) in water under ambient air. This transformation provides direct access to fluorinated indazole derivatives with broad functionalities in satisfactory yields. The experimental results suggest a radical mechanistic pathway of this protocol.

Room-temperature Formal Aza-Wacker Cyclization through Synergistic Copper/TEMPO-catalyzed Radical Relay

A formal aza-Wacker cyclization through a synergistic Cu/TEMPO-catalyzed radical relay pathway, using N-fluorobenzenesulfonimide (NFSI) as an external oxidant, is reported. In this efficient cyclization of alkenylated carbamates or amides at room temperature, the imidyl nitrogen-centered radical (NCR) generated by NFSI induces carbamate or amido NCR from the substrate via N–H homolysis to realize the radical relay process, which was supported by results of control experiments. This work provides an effective approach toward oxazolidinones, pyrrolidones, and isoindolinones under mild conditions.

Catalyst controlled remote C[sbnd]H activation of 8-aminoquinolines with NFSI for C[sbnd]N versus C[sbnd]F coupling

A catalyst-controlled selective functionalization of 8-aminoquinolines with N-fluorobenzenesulfonimide (NFSI) has been developed. The use of GTP-Cu catalysts leads to CN coupling products and whereas the CF coupling reaction is dominant for GPT-Ni catalysis. Importantly, the GPT-Cu and GPT-Ni catalysts exhibit good catalytic activity and selectivity for CN or CF coupling reaction. In addition, it was found that both catalysts still have good activity for coupling reaction after fifth recycle experiment.

Bench-Stable Electrophilic Fluorinating Reagents for Highly Selective Mono- and Difluorination of Silyl Enol Ethers.

Efficient methods for the synthesis of fluorinated compounds have been intensively studied, recently. Development of practical fluorinating reagents is indispensable for this purpose. Herein, bench-stable electrophilic fluorinating reagents were synthesized as N-fluorobenzenesulfonimide (NFSI) substitutes. Reagents obtained by replacing one of the NFSI sulfonyl groups with an acyl group led to the highly selective monofluorination of silyl enol ethers with suppression of undesired overreaction, that is, difluorination. On the other hand, reagents bearing electron-withdrawing substituents at NFSI benzenesulfonyl groups efficiently facilitated the difluorination of silyl enol ethers under base-free conditions. Thus, both mono- and difluorinated target materials were prepared from the same substrate.

Preparation of fluorinated isotactic polypropylene by free radical reaction combining fluorinated reagent and BPO

The incorporation of fluorine into polyolefin can dramatically improve its own mechanical properties and compatibility with other polymers, which has revolutionized the development of polyolefin industry. However, there were no fluorinated isotactic polypropylene (iPP) on the market which remains a formidable challenge. Here, a novel approach is presented that fluorinated iPP was prepared by free radical reaction using N-fluorobenzenesulfonimide (NFSI) as fluorine transfer reagent and benzoyl peroxide (BPO) as initiator in solution reaction. By conducting the tests of water contact angle (CA), DSC and TGA, the results indicated that the surface property and the thermal stability of fluorinated iPP (F-iPP) were greatly improved. In this contribution, a direct and economical route to fluorinate polyolefin was provided.

Selective synthesis of sulfoxides and sulfones via controllable oxidation of sulfides with N-fluorobenzenesulfonimide.

A practical and mild method for the switchable synthesis of sulfoxides or sulfones via selective oxidation of sulfides using cheap N-fluorobenzenesulfonimide (NFSI) as the oxidant has been developed. These highly chemoselective transformations were simply achieved by varying the NFSI loading with H2O as the green solvent and oxygen source without any additives. The good functional group tolerance makes the strategy valuable.

Ligand-free copper-catalyzed C(sp3)-H imidation of aromatic and aliphatic methyl sulfides with N-fluorobenzenesulfonimide.

A novel and efficient process has been developed for copper-catalyzed C(sp3)–H direct imidation of methyl sulfides with N-fluorobenzenesulfonimide(NFSI). Without using any ligands, various methyl sulfides including aromatic and aliphatic methyl sulfides, can be transformed to the corresponding N-((phenylthio)methyl)-benzenesulfonamide derivatives in good to excellent yields.

Site-selective C20-fluorinations of chlorophyll-a derivatives using N-fluorobenzenesulfonimide and their optical properties

Site-selective fluorinations at the C20 position of methyl pyropheophorbides- a , which is derived from naturally occurring chlorophyll(Chl)- a , were achieved by using N -fluorobenzenesulfonimide (NFSI). All the synthetic Chl- a derivatives possessing a variety of the C3-substituents (vinyl, ethyl, formyl, acetyl, hydroxymethyl, and 1-hydroxyethyl groups) were mono-fluorinated to produce the corresponding 20-fluoro-chlorins as isolated products. These fluorinated products were characterized by 1D/2D NMR, visible absorption, and fluorescence emission spectroscopy. Owing to the strong electronegativity of the C20-fluorine atom, their red-most Qy absorption and fluorescence emission bands were bathochromically shifted except for the C3-acetyl substitutes. This study showed not only tolerance of the chlorin π-skeleton and C3-substituents to NFSI but also potential availability of the fluorinated Chl library. • N -Fuorobenzenesulfonimide was useful for fluorination of chlorophyll- a derivatives. • The fluorination site-selectively occurred at the C20 position of chlorin π-system. • The mild fluorination was performed without modification of the C3-substituents. • The electron-withdrawing C20-F partially affected molecular conformations. • The C20-fluorination specifically changed optical properties in solution.

Fluorosulfonylation of arenediazonium tetrafluoroborates with Na2S2O5 and N-fluorobenzenesulfonimide

A transition-metal-free Sandmeyer-type fluorosulfonylation reaction has been achieved by the three-component reaction of arenediazonium tetrafluoroborates, Na2S2O5, and N-fluorobenzenesulfonimide (NFSI). The reaction proceeds through a radical tandem process, affording various arenesulfonyl fluorides in moderate to high yields. This protocol not only provides a complement to the previous fluorosulfonylation reactions, but also extends the applications of Sandmeyer reaction.

A simple and highly efficient synthesis of novel fluorinated 4,6-disubstituted aminopyrimidines using Cd(OAc)2

A highly efficient fluorination reaction of 4,6-disubstituted aminopyrimidines using N-Fluorobenzenesulfonimide (NFSI) has been developed, presumably proceeding via C–H bond activation. Cadmium acetate was employed as the salts, and various fluorinated 4,6-disubstituted aminopyrimidines have been generated in good to excellent yields. This chemistry endows an economical method of valuable fluorinated 4,6-disubstituted aminopyrimidines through a direct C–F bond formation.

Copper-Catalyzed Functionalization of Benzylic C-H Bonds with N-Fluorobenzenesulfonimide: Switch from C-N to C-F Bond Formation Promoted by a Redox Buffer and Brønsted Base.

A copper catalyst in combination with N-fluorobenzenesulfonimide (NFSI) has been reported to functionalize benzylic C-H bonds to the corresponding benzylic sulfonimides via C-N coupling. Here, we reported a closely related Cu-catalyzed method with NFSI that instead leads to C-F coupling. This switch in selectivity arises from changes to the reaction conditions (Cu/ligand ratio, temperature, addition of base) and further benefits from inclusion of MeB(OH)2 in the reaction. MeB(OH)2 is shown to serve as a "redox buffer" in the reaction, responsible for rescuing inactive Cu(II) for continued promotion of fluorination reactivity.

Copper-Catalyzed C-H Fluorination/Functionalization Sequence Enabling Benzylic C-H Cross Coupling with Diverse Nucleophiles.

Site-selective transformation of benzylic C-H bonds into diverse functional groups is achieved via Cu-catalyzed C-H fluorination with N-fluorobenzenesulfonimide (NFSI), followed by substitution of the resulting fluoride with various nucleophiles. The benzyl fluorides generated in these reactions are reactive electrophiles in the presence of hydrogen-bond donors or Lewis acids, allowing them to be used without isolation in C-O, C-N, and C-C coupling reactions.

Copper-catalyzed 1,3-aminothiocyanation of arylcyclopropanes.

A copper-catalyzed 1,3-aminothiocyanation of arylcyclopropanes with N-fluorobenzenesulfonimide (NFSI) and trimethylsilyl isothiocyanate (TMSNCS) has been developed for the first time, efficiently synthesizing a series of γ-aminothiocyanate derivatives in moderate to excellent yields from readily available substrates under mild conditions. The practicability of the reaction was demonstrated by gram-scale preparation. Furthermore, the easily prepared γ-aminothiocyanate derivatives were verified to be versatile building blocks.

Synthesis of Highly Substituted Fluoro Chromenones in a “One‐Pot Four‐ Component Strategy” Using NFSI as a Fluorinating Reagent

AbstractAn efficient one pot four component strategy has been developed for the synthesis of highly substituted fluoro chromenone derivatives (5 a‐p) in good yields from β‐aryl thio acetanilide, aldehydes, cyclic 1,3‐diketones and NFSI (N‐Fluorobenzenesulfonimide) in presence of water. The fluoro imino chromenone intermediate 6 is isolated under the inert condition in high yield.

Direct electrophilic fluorination of naproxen with NF-reagents

A novel effective protocol has been developed for direct fluorination of naproxen using the electrophilic fluorinating reagents 1-chloromethy1-4-fluoro-l,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor™, F-TEDA-BF4) and N-fluorobenzenesulfonimide (NFSI) in MeCN and H2O solvents with the formation of 2-(5-fluoro-6-methoxynaphthalen-2-yl)propionic and 2-(5,5-difluoro-6-oxo-5,6-dihydronaphthalen-2-yl)propionic acids. The reaction of naproxen with an excess of Selectfluor (mol. ratio NF-reagent/naproxen = 2.2) in MeOH gives methyl 2-(5,5-difluoro-6,6-dimethoxy-5,6-dihydronaphthalen-2-yl)propionate as the main product. The mechanistic aspects of the reactions and X-ray data of products are discussed.

Effects of Water Addition on a Catalytic Fluorination of Dienamine.

We investigate the effects of water addition on a highly stereocontrolled fluorination of dienamine generated by α-branched enals and 6′-hydroxy-9-amino-9-deoxy-epi-quinidine with N-fluorobenzenesulfonimide (NFSI) in the presence of Brønsted acid both experimentally and theoretically. It is experimentally found that water addition to organic solvent significantly shortens the reaction time whereas excessive water addition decreases the enantiomeric excess. The results calculated with three-dimensional reference interaction site model self-consistent field (3D-RISM-SCF) method are in good agreement with the experimental ones. It is revealed that the shortness of reaction time is caused by the reactant destabilization and that the decrease in enantiomeric excess is due to the difference of hydration free energy between two transition states.

Direct and Regioselective Monofluorination of N-Protected Pyridone Derivatives using N-Fluorobenzenesulfonimide (NFSI).

The direct monofluorination of N-protected pyridone derivatives has been developed using a stable electrophilic fluorinating reagent, N-fluorobenzenesulfonimide (NFSI). Interestingly, the fluorine atom is regioselectively introduced at the position opposite the carbonyl group in the pyridone substrate during the reaction. This method is applicable to a wide range of substrates and allows the regioselective late-stage monofluorination of pyridone scaffolds.

Electrostatic Effects Accelerate Decatungstate-Catalyzed C–H Fluorination Using [18F]- and [19F]NFSI in Small Molecules and Peptide Mimics

The site-selective fluorination of unactivated C(sp3)-H bonds provides unique opportunities to rapidly alter drug properties or generate radiotracers for positron emission tomography (PET) imaging. Toward this goal, photoactivated decatungstate (DT) is capable of generating carbon radicals through hydrogen atom transfer that subsequently undergo fluorination by reaction with N-fluorobenzenesulfonimide (NFSI) or [18F]NFSI. This process enables C(sp3)-H fluorination of a wide range of aliphatic compounds, though reaction rates can be highly variable and limit applications in radiotracer synthesis. Here, we demonstrate that cationic ammonium functions in aliphatic molecules promote formation of a precursor complex with DT that significantly increases the rate of C–H abstraction. The general utility of this rate-accelerating electrostatic effect is demonstrated on more than 30 ammonium-containing molecules, including amino acids, heterocycles, and pseudopeptides. Moreover, this effect is highlighted in the ra...

Room‐Temperature C‐H Bromination and Iodination with Sodium Bromide and Sodium Iodide Using N‐Fluorobenzenesulfonimide as an Oxidant

AbstractA transition‐metal‐free electrophilic bromination and iodination of arene through C−H cleavage at room temperature has been developed in excellent to quantitative yields with broad arene scope and good regioselectivity, in which environment‐benign and readily available sodium halides, NaBr or NaI, were employed as halogen sources in accompany with N‐fluorobenzenesulfonimide (NFSI) as an oxidant. Studies have also demonstrated that, in this air‐ and moisture‐resistant scalable halogenation under mild conditions, the oxidant NFSI is reduced to dibenzenesulfonimide which usually serves as the starting material for the preparation of NFSI, rendering this facile and versatile protocol promising potentials for future applications in organic synthesis.

Synthesis of α‐Fluoroamides with a C–F Quaternary Stereogenic Center by Electrophilic Fluorination: One‐Pot Four‐Component Strategy

An efficient method for the synthesis of α‐fluoroamides having C–F quaternary stereogenic center was achieved by a one‐pot four‐component strategy under mild reaction conditions. A variety of α‐fluoroamides was synthesized by using 1,3‐dicarbonyl, isocyanide, acetylenedicarboxylate and N‐fluorobenzenesulfonimide (NFSI) systems with good to excellent yields up to 93 %. The current protocol proceeds through the unstable 3‐fluoro 4H‐pyran intermediate, which is key for the reaction and further it can be hydrolyzed due to the high electronegativity of the fluorine atom to produce the desired α‐fluoroamides.