Triflic Anhydride Research Articles

A Fluorescent Linear Conjugated Polymer Constructed from Pillararene and Anthracene.

Over the past few years, conjugated polymers (CPs) have aroused much attention owing to their rigid conjugated structures, which can perform well in light harvesting and energy transfer and offer great potential in materials chemistry. In this article, we fabricate a new luminescent linear CP p(P[5](OTf)2-co-9,10-dea) via the Sonogashira coupling of 9,10-diethynylanthracene and trifluoromethanesulfonic anhydride (OTf) modified pillar[5]arene, generating enhanced yellow-green fluorescence emission at around 552 nm. The reaction condition was screened to get a deeper understanding of this polymerization approach, resulting in an excellent yield as high as 92% ultimately. Besides the optical properties, self-assembly behaviors of the CP in low/high concentrations were studied, where interesting adjustable morphologies from tube to sheet were observed. In addition, the fluorescence performance and structural architecture can be disturbed by the host–guest reorganization between the host CP and the guest adiponitrile, suggesting great potential of this CP material in the field of sensing and detection.

The First Anionic Thia‐Fries Rearrangement at the Cobaltocenium Cation

While the chemistry of ferrocene is rich and widely explored, this is not the case for the isoelectronic cobaltocenium cation. Here we report the first syntheses of triflate substituted cobaltocenium cations based on respective (cyclopentadienone)(cylopentadienyl)cobalt(I) complexes, which have first been reported by Vollhardt et al. ca. forty years ago. Reaction with triflic anhydride affords the triflate substituted cobaltocenium cations, which upon treatment with lithium diisopropylamide undergo the first anionic thia-Fries rearrangements of cobaltocenium complexes. To our knowledge, this is, in addition, the first case of a deprotonation of a cobaltocenium complex by a lithium base. Alternatively, desilylation of silyl derivatives with cesium fluoride caused anion formation leading to the rearrangement products in higher yields. The 2-(trifluoromethylsulfonyl)(cyclopentadienone) complexes obtained were fully characterized including a crystal structure analysis. As with ferrocene, respective mesylates or tosylates do not undergo the rearrangement.

Synthesis of the Icetexane Diterpenoids (±)-Rosmaridiphenol, (±)-Pisiferin, and (±)-Barbatusol from Abietane

AbstractWe report the rearrangement of abietane core with trifluoromethanesulfonic anhydride in pyridine to afford the icetexane core, a key intermediate for total syntheses of the structurally intriguing and biologically active compounds (±)-barbatusol, (±)-rosmaridiphenol, and (±)-pisiferin.

Triflic Anhydride (Tf2O)-Activated Transformations of Amides, Sulfoxides and Phosphorus Oxides via Nucleophilic Trapping

AbstractTrifluoromethanesulfonic anhydride (Tf2O) is utilized as a strong electrophilic activator in a wide range of applications in synthetic organic chemistry, leading to the transient generation of a triflate intermediate. This versatile triflate intermediate undergoes nucleophilic trapping with diverse nucleophiles to yield novel compounds. In this review, we describe the features and applications of triflic anhydride in organic synthesis reported in the past decade, especially in amide, sulfoxide, and phosphorus oxide chemistry through electrophilic activation. A plausible mechanistic pathway for each important reaction is also discussed.1 Introduction2 Amide Chemistry2.1 Carbon Nucleophiles2.2 Hydrogen Nucleophiles2.3 Nitrogen Nucleophiles2.4 Oxygen and Sulfur Nucleophiles2.5 hosphorus Nucleophiles2.6 A Vilsmeier-Type Reagent2.7 Umpolung Reactivity in Amides3 Sulfoxide Chemistry3.1 Oxygen Nucleophiles3.2 Carbon Nucleophiles3.3 Nitrogen Nucleophiles3.4 Thionium Reagents4 Phosphorus Chemistry4.1 Hendrickson’s Reagent4.2 Diaryl Phosphine Oxides4.3 Phosphonates, Phosphates and Phosphinates5 Conclusion and Outlook

Retro Baeyer-Villiger reaction: thermal conversion of the [60]fullerene-fused lactones to ketones.

The conversion of the [60]fullerene-fused lactones to ketones with triflic anhydride as an unusual reductant under aerobic conditions has been achieved in excellent yields. The present thermal retro Baeyer-Villiger reaction from lactones to ketones has no precedents. In addition, the unique ring-opened peroxy [60]fullerene derivatives can be obtained by the electrochemical reactions of the synthesized [60]fullerene-fused ketones.

Direct C–H-sulfonylation of 6-membered nitrogen-heteroaromatics

Heterocyclic sulfones and sulfonamides represent important structural motives in medicinal chemistry and drug development. Therefore, efficient and reliable methods for their construction from simple building blocks are in high demand. Herein we report a novel approach for the direct C–H-sulfonylation of N-heteroaromatics via N-activation with triflic anhydride (Tf2O), base-mediated addition of a sulfinate salt and subsequent rearomatization through trifluoromethanesulfinate elimination. This operationally simple one-pot protocol enables direct access to various sulfonylated 6-ring N-heterocycles. It is applicable to the late-stage functionalization of complex, drug-like molecules. The direct incorporation of sulfur dioxide with organometallic reagents as well as the utilization of a rongalite-based sulfonylation reagent provide opportunities for a highly modular synthesis of N-heterocyclic sulfones and sulfonamides from three different building blocks.

Ammonium Pertechnetate in Mixtures of Trifluoromethanesulfonic Acid and Trifluoromethanesulfonic Anhydride.

Ammonium pertechnetate reacts in mixtures of trifluoromethanesulfonic anhydride and trifluoromethanesulfonic acid under final formation of ammonium pentakis(trifluoromethanesulfonato)oxidotechnetate(V), (NH4)2[TcO(OTf)5]. The reaction proceeds only at exact concentrations and under the exclusion of air and moisture via pertechnetyl trifluoromethanesulfonate, [TcO3(OTf)], and intermediate TcVI species. 99Tc nuclear magnetic resonance (NMR) has been used to study the TcVII compound and electron paramagnetic resonance (EPR), 99Tc NMR and X‐ray absorption near‐edge structure (XANES) experiments indicate the presence of the reduced technetium species. In moist air, (NH4)2[TcO(OTf)5] slowly hydrolyses under formation of the tetrameric oxidotechnetate(V) (NH4)4[{TcO(TcO4)4}4] ⋅10 H2O. Single‐crystal X‐ray crystallography was used to determine the solid‐state structures. Additionally, UV/Vis absorption and IR spectra as well as quantum chemical calculations confirm the identity of the species.

Ammonium Pertechnetate in Mixtures of Trifluoromethanesulfonic Acid and Trifluoromethanesulfonic Anhydride

AbstractAmmonium pertechnetate reacts in mixtures of trifluoromethanesulfonic anhydride and trifluoromethanesulfonic acid under final formation of ammonium pentakis(trifluoromethanesulfonato)oxidotechnetate(V), (NH4)2[TcO(OTf)5]. The reaction proceeds only at exact concentrations and under the exclusion of air and moisture via pertechnetyl trifluoromethanesulfonate, [TcO3(OTf)], and intermediate TcVI species. 99Tc nuclear magnetic resonance (NMR) has been used to study the TcVII compound and electron paramagnetic resonance (EPR), 99Tc NMR and X‐ray absorption near‐edge structure (XANES) experiments indicate the presence of the reduced technetium species. In moist air, (NH4)2[TcO(OTf)5] slowly hydrolyses under formation of the tetrameric oxidotechnetate(V) (NH4)4[{TcO(TcO4)4}4] ⋅10 H2O. Single‐crystal X‐ray crystallography was used to determine the solid‐state structures. Additionally, UV/Vis absorption and IR spectra as well as quantum chemical calculations confirm the identity of the species.

Divergent Synthesis of α-Fluorinated Carbonyl and Carboxyl Derivatives by Double Electrophilic Activation of Amides.

A straightforward and divergent entry to α-fluorinated carbonyl and carboxyl derivatives is reported. Upon activation of amides with triflic anhydride and a 2-halo-pyridine and subsequent trapping of the resulting keteniminium ions with nucleophiles followed by a second electrophilic activation with NFSI and final hydrolysis, a range of amides can be transformed to α-fluorinated ketones, esters, and amides under mild conditions. Moreover, this reaction can be performed to yield enantioenriched products with a traceless chiral auxiliary.

One-Pot Synthesis of CF3-Substituted Vinyl Trifluoromethanesulfonamides from Imines and Trifluoromethanesulfonic Anhydride.

The one-pot triflation/radical trifluoromethylation/triflation of imines leading to CF3-substituted vinyl trifluoromethanesulfonamides is described. The reaction proceeds via the radical trifluoromethylation of vinyl trifluoromethanesulfonamides as the key step. This reaction is suitable for a variety of imines that contain halogen atoms, electron-donating groups, or electron-withdrawing groups, leading to moderate to good yields. Vinyl trifluoromethanesulfonamides can act as bifunctional reagents whereby they serve as both the trifluoromethyl radical source and the radical acceptor.

Synthesis of 1-(1-Arylvinyl)pyridin-2(1H)-ones from Ketones and 2-Fluoropyridine

We describe a simple and efficient procedure for the synthesis of N-vinyl-substituted pyridones from ketones and 2-fluoropyridine in the presence of trifluoromethane sulfonic anhydride, followed by a base treatment. Various ketones with electron-donating or electron-withdrawing groups at the benzene rings can be used in this reaction. A preliminary mechanistic study indicates that it is not very likely that both vinyl triflates and vinyl cations play major roles as intermediates in this transformation.

Mechanochemical Solvent-Free Synthesis of Indenones from Aromatic Carboxylic Acids and Alkynes.

The mechanochemical solvent-free synthesis of indenones from aromatic carboxylic acids and alkynes was achieved through triflic anhydride (Tf2O)-induced cyclization reaction. A variety of indenones including a bioactive PPARγ agonist were obtained in up to 90% yield at room temperature. The present protocol has the advantages of mild reaction conditions, high reaction efficiency, and feasibility of scalable synthesis, providing a facile and sustainable route to diverse indenones.

Direct Synthesis of Enamides via Electrophilic Activation of Amides.

A novel, one-step N-dehydrogenation of amides to enamides is reported. This reaction employs the unlikely combination of LiHMDS and triflic anhydride, which serves as both the electrophilic activator and the oxidant, and is characterized by its simple setup and broad substrate scope. The synthetic utility of the formed enamides was readily demonstrated in a range of downstream transformations.

An Efficient and Practical Chemoenzymatic Route to (3R,3aR,6R,6aR)-Hexahydrofuro[3,2-b]furan-6-amino-3-ol (6-Aminoisomannide) from Renewable Sources

AbstractThe synthesis of 6-aminoisomannide is easily achieved starting from the renewable, inexpensive, and commercially available isosorbide in 66% overall yield. A biocatalyzed highly regioselective acetylation of the 3-endo hydroxyl group of isosorbide was followed by the stereospecific interconversion of the 6-exo hydroxyl group into an azido group, through reaction with trifluoromethanesulfonic anhydride, followed by nucleophilic displacement of the triflate group by sodium azide. Finally, reduction of the azido group and deacetylation of the 3-hydroxy group were performed in one pot using LiAlH4.

Triflic Anhydride (Tf2O): An Efficient Catalyst for Electrophilic Activation of Amides

AbstractTf2O (trifluoromethanesulfonic anhydride) as an electrophilic reagent has been increasingly attracting the attention of researchers over the last decade due to its capability in synthesizing a variety of N‐heterocycles through activation of amides. This activation is associated with the formation of intermediates such as enolonium, imino/iminium, nitrilium and keteniminium triflate ions and isocyanate species which can lead to the synthesis of different types of N‐heterocycles depending on the nature of the intermediates. In this review, we have summarized and classified the latest research in this area (from 2012 on) based on the type of intermediates produced from the triflic anhydride‐catalyzed activation of amides. The findings are classified into five main categories, namely enolonium, imino/iminium, nitrilium and keteniminium intermediates ions and isocyanate species.

Trifluoromethyl Thianthrenium Triflate: A Readily Available Trifluoromethylating Reagent with Formal CF3+, CF3•, and CF3– Reactivity

Here we report the synthesis and application of trifluoromethyl thianthrenium triflate (TT-CF3+OTf–) as a novel trifluoromethylating reagent, which is conveniently accessible in a single step from thianthrene and triflic anhydride. We demonstrate the use of TT-CF3+OTf– in electrophilic, radical, and nucleophilic trifluoromethylation reactions.

One-pot synthesis of dihydropyridine carboxylic acids via functionalization of 3-((trimethylsilyl)ethynyl)pyridines and an unusual hydration of alkynes: Molecular docking and antifungal activity

Activation of 3-((trimethylsilyl)ethynyl)pyridine with triflic anhydride followed by nucleophilic addition of bis(trimethylsili) ketene acetals and a unusual alkyne hydration allowed to obtain new series of 3-acetylated dihydropyridine acids 3a-h in a single step. Secondly, docking studies were conducted on four of the test compounds ( 3b , 3e , 17a and 17b ) and a reference drug (fluconazole) at the active site of lanosterol 14α-demethylase enzymes (CYP51) from Candida spp., in vitro inhibition assays were performed with the same compounds and yeast species. Compounds 3b , 3e , 17a and 17b interacted with key amino acids of the active site of CYP51 enzymes in a similar manner as fluconazole. Compared to fluconazole, the test compounds showed better binding energy values (−4.84 to −9.1 vs. −1.51 to 5.68 kcal/mol) and in vitro antifungal activity (lower MIC values) on different Candida species. Hence, the dihydropyridine derivatives can be considered candidates for the development of new antifungal drugs. • Dihydropyridines. • Hydration of alkynes. • Molecular docking. • antifungal activity. • Candida spp.

Divergent, Strain‐Release Reactions of Azabicyclo[1.1.0]butyl Carbinols: Semipinacol or Spiroepoxy Azetidine Formation

AbstractThe azetidine moiety is a privileged motif in medicinal chemistry and new methods that access them efficiently are highly sought after. Towards this goal, we have found that azabicyclo[1.1.0]butyl carbinols, readily obtained from the highly strained azabicyclo[1.1.0]butane (ABB), can undergo divergent strain‐release reactions upon N‐activation. Treatment with trifluoroacetic anhydride or triflic anhydride triggered a semipinacol rearrangement to give keto 1,3,3‐substituted azetidines. More than 20 examples were explored, enabling us to evaluate selectivity and the migratory aptitude of different groups. Alternatively, treatment of the same alcohols with benzyl chloroformate in the presence of NaI led to iodohydrin intermediates which gave spiroepoxy azetidines upon treatment with base. The electronic nature of the activating agent dictates which pathway operates.

Divergent, Strain-Release Reactions of Azabicyclo[1.1.0]butyl Carbinols: Semipinacol or Spiroepoxy Azetidine Formation.

The azetidine moiety is a privileged motif in medicinal chemistry and new methods that access them efficiently are highly sought after. Towards this goal, we have found that azabicyclo[1.1.0]butyl carbinols, readily obtained from the highly strained azabicyclo[1.1.0]butane (ABB), can undergo divergent strain‐release reactions upon N‐activation. Treatment with trifluoroacetic anhydride or triflic anhydride triggered a semipinacol rearrangement to give keto 1,3,3‐substituted azetidines. More than 20 examples were explored, enabling us to evaluate selectivity and the migratory aptitude of different groups. Alternatively, treatment of the same alcohols with benzyl chloroformate in the presence of NaI led to iodohydrin intermediates which gave spiroepoxy azetidines upon treatment with base. The electronic nature of the activating agent dictates which pathway operates.

A BECKMANN REARRANGEMENT INITIATED BY TRIFLUOROMETHANESULFONIC ANHYDRIDE IN THE SYNTHESIS OF COMPOUNDS CONTAINING A NEW PYRAZOLO[3',4':5,6]PYRIDO[3,2- b ]AZEPINE HETEROCYCLIC SYSTEM

N -Boc-5-formylpyrazol-4-amines reacted with 1,3-cyclohexanediones in AcOH–1,4-dioxane medium in the presence of pyrrolidine, resulting in the formation of pyrazolo[4,3- b ]quinolin-8-one derivatives that were converted into the respective oximes. A reaction of the latter with trifluoromethanesulfonic anhydride under mild conditions was used to synthesize hexahydropyrazolo[3',4':5,6]pyrido[3,2- b ]azepin-4-ium trifluoromethanesulfonates.