Pyridinium Triflate Research Articles

Towards the synthesis of a 2-deoxy-2-fluoro-d-mannose building block and characterisation of an unusual 2-S-phenyl anomeric pyridinium triflate salt via 1 → 2 S-migration

Regio- and stereo-selective synthetic routes to 2-deoxy-2-fluoro-d-mannose building blocks are often experimentally challenging when using Selectfluor with the corresponding glycal. We targeted a late-stage method to introduce fluorine in a stereospecific manner using inversion via a triflate. Accordingly, synthesis of a conventionally protected 2-deoxy-2-fluoro-d-mannose β-thioglycoside donor, directly applicable to oligosaccharide synthesis, was attempted using C2-triflate inversion of the corresponding d-glucoside with TBAF. Unexpectedly, an anomeric pyridinium salt was isolated when attempting to form the C2-triflate using Tf2O in pyridine. Indicatively, this proceeds via a 1 → 2 S-migration delivering a 1,2-trans product with α-d-manno configuration and the anomeric pyridinium in a pseudo-equatorial position. The structure of this unexpected intermediate was confirmed in the solid-state using X-ray crystallography. Omission of the pyridine solvent led to dimer formation. Switching the aglycone to an O-para-methoxyphenyl enabled smooth C2 inversion to the desired 2-deoxy-2-fluoro d-mannose system, suitably equipped for further anomeric manipulation.

Enantioselective Dearomatization of Pyridinium Salts by Copper-Catalyzed C4-Selective Addition of Silicon Nucleophiles.

A copper-catalyzed C4-selective addition of silicon nucleophiles released from an Si-B reagent to prochiral pyridinium triflates is reported. The dearomatization proceeds with excellent enantioselectivity using Cu(CH3CN)4PF6 as the precatalyst and (R,R)-Ph-BPE (1,2-bis[(2R,5R)-2,5-diphenylphospholan-1-yl]ethane) as the chiral ligand. A carbonyl group at C3 is required for this, likely acting a weak donor group to preorganize and direct the nucleophilic attack towards C4. The resulting 4-silylated 1,4-dihydropyridines can be further converted into functionalized piperidine derivatives.

Enantioselective Dearomatization of Pyridinium Salts by Copper‐Catalyzed C4‐Selective Addition of Silicon Nucleophiles

A copper‐catalyzed C4‐selective addition of silicon nucleophiles released from an Si–B reagent to prochiral pyridinium triflates is reported. The dearomatization proceeds with excellent enantioselectivity using Cu(CH3CN)4PF6 as the precatalyst and (R,R)‐Ph‐BPE as the chiral ligand. A carbonyl group at C3 is required, likely acting a weak group to preorganize and direct the nucleophilc attack towards C4. The resulting 4‐silylated 1,4‐dihydropyridines can be further converted into functionalized piperidine derivatives.

Photoredox Trifluoromethylation/Cyclization of N-Arylacrylamides with 4-(Difluoroamino)-1-[(trifluoromethyl)sulfonyl]pyridinium Triflate (TFSP)

AbstractA photoredox trifluoromethylation/cyclization of N-arylacrylamides with inexpensive stable solid 4-(difluoroamino)-1-[(trifluoromethyl)sulfonyl]pyridinium triflate (TFSP) has been developed.

Insight into the Modes of Activation of Pyridinium and Bipyridinium Salts in Non‐Covalent Organocatalysis

AbstractA series of pyridinium and bipyridinium salts were prepared and their catalytic properties were evaluated in the aza‐Diels‐Alder reaction between imines and Danishefsky diene. Depending on the substituents of the pyridinium/bipyridinium rings and on the nature of the counterion, two mechanisms of activation were demonstrated. In case of non‐substituted rings, the substrate is activated through charge transfer involving the aryl ring on the C‐side of the imine. When halogen atoms were introduced on the catalysts, the activation mode switched to halogen bond involving the imine nitrogen lone pair. Moreover, alternative activation modes based on hydrogen bonding and radical cation were ruled out. This work allowed us to develop two families of catalysts whose potential was demonstrated in the cycloaddition of various imines with Danishefsky diene. The first family is composed of the simple methyl pyridinium triflate and dioctyl bipyridinium triflate. The former is active only with imines bearing a p‐methoxyphenyl group on the C‐side and the latter was found to be efficient with imines bearing different substituents on both the N‐ and C‐sides of the imines. The second family is based on halogenated pyridinium salts which proved active with almost all considered imines.magnified image

Pyridinium triflate catalyzed intramolecular alkyne-carbonyl metathesis reaction of O-propargylated 2-hydroxyarylaldehydes

3,5-Dibromopridinium trifluoromethanesulfonate catalyzes the intramolecular alkyne-carbonyl metathesis reaction of a variety of O-propargylated 2-hydroxyarylaldehydes and ketones bearing alkyl, aryl and heteroaryl substituted internal alkynes to provide various 3-(hetero)aroyl 2H-chromenes in high yields.

4-Hydroxy Pyridinium Triflate@SiO2 Nanoparticles as a Novel Efficient Catalyst for Fries Rearrangement of Aryl Esters with High Selectivity.

We developed a simple, fast and new method for the Fries rearrangement of aryl esters. 4-Hydroxy pyridinium triflate functionalized silica is a very efficient, reusable and economically available catalyst for the Fries rearrangement in solvent-free condition and under microwave irradiation. Also, a notable selectivity was observed in the presence of 4-hydroxy pyridinium triflate functionalized silica. Selectivity, shorter reaction time, high yield, and easy work-up are advantages of this synthetic method.

Charge Transport in Nonstoichiometric 2-Fluoropyridinium Triflate Protic Ionic Liquids

Pyridinium triflate protic ionic liquids have been demonstrated to be highly dissociated, and nonstoichiometric compositions have been used in protic energy devices such as the all-organic proton battery. Herein, we use a combination of pulsed field gradient NMR spectroscopy and electrochemical impedance spectroscopy to investigate the charge transport properties of the nonstoichiometric protic ionic liquid 2-fluoropyridinium triflate and the variation with acid doping level. While all diffusion coefficients decreased with the amount of acid doping, the room temperature conductivity increased due to the concurrent increase in charge carrier concentration. The maximum room temperature conductivity was 7.33 mS/cm, obtained when 14% of the pyridine was protonated with triflic acid, while higher acid doping levels lead to liquid/solid mixtures with low conductivity. PEDOT supercapacitor cells with this electrolyte demonstrated very high capacitance (83.9 F/g) and charge storage capacity (23.3 mAh/g). In addition we predict that using a lower acid doping level than previously will result in superior electrolyte performance in proton batteries due to improvements in conductivity, processability and electrochemical stability. (Less)

Electrochromic behavior of films and «smart windows» prototypes based on π-conjugated and non–conjugated poly(pyridinium triflate)s

This study is focused on two electrochromic poly(pyridinium triflate)s. They are aromatic rigid-rod polymer PV1 and PV12 containing alkyl linkages. Electrochromic behavior of both polymers was comparatively investigated by employing a three-electrode cell and «smart windows» prototypes. The electrochromic properties of polymer films were examined by electrochemical and spectroelectrochemical methods. Polymers with π-conjugate and non-conjugate structure demonstrate reversible redox process accompanied by a reversible color change both in three-electrode cell and electrochromic device (ECD). In general, introduction of the non-conjugated spacers to the PV12 backbone structure leads to deterioration in the optical contrast and switching time in comparison with π-conjugated PV1. The same effect was also detected for ECD. The reason behind this is thought to be a complication of electron transport in the system due to non-conjugated PV12 backbone structure.

Electrochromic behavior and electrical percolation threshold of carbon nanotube/poly(pyridinium triflate) composites

The electrochromic composite material based on poly(4,4′-(1,4-phenylene)bis(2,6-diphenylpyridinium) triflate) (PV) and multiwall carbon nanotubes (MWCNTs) was prepared by non-covalent interaction where PV acts as a functionalizing agent for MWCNTs. The increase in electrical conductivity and improvement of electrochromic properties of PV is attributed to the formation of MWCNTs networks. The percolation threshold for PV/MWCNTs occurred at 0.3 wt% of MWCNTs. Corresponding value of critical exponent was found to be 2.8 which is far from universal values. At practically the same electrochromic contrast the coloring and bleaching time for composites with higher polymer concentration (8 mg/mL) decreased from 600 ms to 300 ms and from 500 ms to 350 ms, respectively. It was demonstrated that further increase of MWCNTs weight content did not lead to the improvement of electrochromic properties.

Synthesis, Characterization, and Computational Modeling of N-(1-Ethoxyvinyl)pyridinium Triflates, an Unusual Class of Pyridinium Salts.

N-Substituted pyridinium salts constitute one of the most valuable reagent classes in organic synthesis, due to their versatility and ease of use. Herein we report a preliminary synthesis and detailed structural analysis of several N-(1-ethoxyvinyl)pyridinium triflates, an unusual class of pyridinium salts with potentially broad use as a reagent in organic synthesis. Treatment of pyridines with trifluoromethane sulfonic acid and ethoxyacetylene generates stable, isolable adducts which have been extensively characterized, due to their novelty. Three-dimensional structural stability is perpetuated by an array of C–H•••O hydrogen bonds involving oxygen atoms from the –SO3 groups of the triflate anion, and hydrogen atoms from the aromatic ring and vinyl group of the pyridinium cation. Predictions from density functional theory calculations of the energy landscape for rotation about the exocyclic C–N bond of 2-chloro-1-(1-ethoxyvinyl)pyridine-1-ium trifluoromethanesulfonate (7) and 1-(1-ethoxyvinyl)pyridine-1-ium trifluoromethanesulfonate (16) are also reported. Notably, the predicted global energy minimum of 7 was nearly identical to that found within the crystal structure.

Brønsted Acid Catalyzed Synthesis of Functionalized 1,4- and 1,6-Dicarbonyl Monosilyl Enol Ethers under Operationally Practical Conditions.

Herein, we report an improved protocol for the concise synthesis of functionalized 1,4- and 1,6-dicarbonyl-derived monosilyl enol ethers via ionization of α'-hydroxy silyl enol ethers to generate unsymmetrical silyloxyallyl cations that were subsequently captured by TBS silyl enolates. These transformations were efficiently performed in acetonitrile at room temperature by employing pyridinium triflate as a catalyst. Our new reaction conditions are operationally more practical and broaden the accessibility of various 1,4- and 1,6-dicarbonyl groups, which include diketone, ketoester, and ketothioester functionalities.

An All-Organic Proton Battery

Rechargeable batteries that use organic matter as the capacity-carrying material have previously been considered a technology for the future. Earlier batteries in which both the anode and cathode consisted of organic material required significant amounts of conductive additives and were often based on metal-ion electrolytes containing Li+ or Na+. However, we have used conducting poly(3,4-ethylenedioxythiophene) (PEDOT), functionalized with anthraquinone (PEDOT-AQ) or benzonquinone (PEDOT-BQ) pendant groups as the negative and positive electrode materials, respectively, to make an all-organic proton battery devoid of metals. The electrolyte consists of a proton donor and acceptor slurry containing substituted pyridinium triflates and the corresponding pyridine base. This slurry allows the 2e-/2H+ quinone/hydroquinone redox reactions while suppressing proton reduction in the battery cell. By using strong (acidic) proton donors, the formal potential of the quinone redox reactions is tuned into the potential region in which the PEDOT backbone is conductive, thus eliminating the need for conducting additives. In this all-organic proton battery cell, PEDOT-AQ and PEDOT-BQ deliver 103 and 120 mAh g-1, which correspond to 78% and 75%, respectively, of the theoretical specific capacity of the materials at an average cell potential of 0.5 V. We show that PEDOT-BQ determines the cycling stability of the device while PEDOT-AQ provides excellent reversibility for at least 1000 cycles. This proof-of-concept shows the feasibility of assembling all-organic proton batteries which require no conductive additives and also reveals where the challenges and opportunities lie on the path to producing plastic batteries.

Synthesis, characterization, DNA-Binding, enzyme inhibition and antioxidant studies of new N-methylated derivatives of pyridinium amine

A series of novel N-methylated derivatives of pyridinium amine, [L1][Tf]-[L5][Tf], were synthesized and characterized by FTIR, NMR, MS and XRD analyses. Preliminary biological screening of these compounds including antioxidant, enzyme inhibition and DNA (salmon sperm) interaction studies were also carried out. The targeted compounds were synthesized by a melt reaction between 4-chloro-N-methyl pyridinium triflate and corresponding amines (1-naphthyl amine, o-ansidine, 2-nitroaniline, p-ansidine and cyclohexyl amine) at temperature of 230 °C. The DPPH radical antioxidant scavenging activities of these compounds at maximum concentration of 50 μg/mL were observed in the range of 60–70%. Acetylcholine esterase (AChE) and Butylcholine esterase (BChE) inhibitory activities of synthesized compounds at 2 mM concentration were also measured to be at maximum of 79 and 71% respectively. The spectral behavior of ligand-DNA obtained from photo-luminescent measurements showed that all ligands bind with DNA via non-covalent interactions. The binding constant values were determined by UV–visible and fluorescence spectroscopy and were quite close to that obtained from molecular docking studies.

An Improved Synthesis of Lamivudine and Emtricitabine

AbstractAn improved method was developed to prepare cis(‐)nucleosides, such as lamivudine (3TC) and emtricitabine (FTC). A solvent free reaction and catalyst free reaction was developed, with reduced reaction times to afford high yields in the preparation of the key 5‐hydroxy oxathiolane intermediate. For the acetylation, we developed a greener procedure using NaHCO3 as the base instead of pyridine. In addition, a new reagent namely pyridinium triflate, was used for the crucial N‐glycosidation reaction for the first time towards the synthesis of bioactive oxathiolane nucleosides 3TC and FTC.

Pyridylidene-Mediated Dihydrogen Activation Coupled with Catalytic Imine Reduction.

In recent years, dihydrogen activation at non-metallic centers has received increasing attention. A system in which dihydrogen is trapped by a pyridylidene intermediate that is generated from a pyridinium salt and a base is now reported. The dihydropyridine formed in this process can act as reducing agent towards organic electrophiles. By coupling the hydrogen-activation step with subsequent hydride transfer from the dihydropyridine to an imine, a catalytic process was established. Treatment of the N-phenylimine of phenyl trifluoromethyl ketone with 5-20 mol% of N-mesityl-3,5-bis(2,6-dimethylphenyl)pyridinium triflate and 0.3-1.0 equivalents of LiN(SiMe3)2 under 50 bar of hydrogen gas resulted in high conversion into the corresponding amine.

Pyridylidene-Mediated Dihydrogen Activation Coupled with Catalytic Imine Reduction

In recent years, dihydrogen activation at non-metallic centers has received increasing attention. A system in which dihydrogen is trapped by a pyridylidene intermediate that is generated from a pyridinium salt and a base is now reported. The dihydropyridine formed in this process can act as reducing agent towards organic electrophiles. By coupling the hydrogen-activation step with subsequent hydride transfer from the dihydropyridine to an imine, a catalytic process was established. Treatment of the N-phenylimine of phenyl trifluoromethyl ketone with 5–20 mol % of N-mesityl-3,5-bis(2,6-dimethylphenyl)pyridinium triflate and 0.3–1.0 equivalents of LiN(SiMe3)2 under 50 bar of hydrogen gas resulted in high conversion into the corresponding amine.

Electron-deficient heteroarenium salts: an organocatalytic tool for activation of hydrogen peroxide in oxidations.

A series of monosubstituted pyrimidinium and pyrazinium triflates and 3,5-disubstituted pyridinium triflates were prepared and tested as simple catalysts of oxidations with hydrogen peroxide, using sulfoxidation as a model reaction. Their catalytic efficiency strongly depends on the type of substituent and is remarkable for derivatives with an electron-withdrawing group, showing reactivity comparable to that of flavinium salts which are the prominent organocatalysts for oxygenations. Because of their high stability and good accessibility, 4-(trifluoromethyl)pyrimidinium and 3,5-dinitropyridinium triflates are the catalysts of choice and were shown to catalyze oxidation of aliphatic and aromatic sulfides to sulfoxides, giving quantitative conversions, high preparative yields and excellent chemoselectivity. The high efficiency of electron-poor heteroarenium salts is rationalized by their ability to readily form adducts with nucleophiles, as documented by low pKR+ values (pKR+ < 5) and less negative reduction potentials (Ered > -0.5 V). Hydrogen peroxide adducts formed in situ during catalytic oxidation act as substrate oxidizing agents. The Gibbs free energies of oxygen transfer from these heterocyclic hydroperoxides to thioanisole, obtained by calculations at the B3LYP/6-311++g(d,p) level, showed that they are much stronger oxidizing agents than alkyl hydroperoxides and in some cases are almost comparable to derivatives of flavin hydroperoxide acting as oxidizing agents in monooxygenases.

Brønsted acid catalyzed α'-functionalization of silylenol ethers with indoles.

A new method which enables carbon-carbon bond formation at the α'-position of silylenol ethers by using catalytic amounts of pyridinium triflate is reported. This chemistry successfully produces, structurally challenging, highly substituted indole-containing silylenol ethers in excellent yields with complete regiocontrol, presumably through silyloxyallyl cation intermediates. Despite the use of Brønsted acid, the silylenol ether moiety does not undergo protodesilylation, thus underscoring the very mild reaction conditions.

Brønsted Acid Catalyzed α′‐Functionalization of Silylenol Ethers with Indoles

AbstractA new method which enables carbon–carbon bond formation at the α′‐position of silylenol ethers by using catalytic amounts of pyridinium triflate is reported. This chemistry successfully produces, structurally challenging, highly substituted indole‐containing silylenol ethers in excellent yields with complete regiocontrol, presumably through silyloxyallyl cation intermediates. Despite the use of Brønsted acid, the silylenol ether moiety does not undergo protodesilylation, thus underscoring the very mild reaction conditions.