Vinyl Ether Research Articles

Visible-Light-Induced Intermolecular Trifluoromethyl Heteroarylation of Vinyl Ethers for the Syntheses of β-Trifluoromethyl Alkyl Thiochromones.

Herein, we reported a transition-metal-free three-component trifluoromethyl heteroarylation of vinyl ethers under visible light irradiation. This protocol proceeded through a radical addition/cyclization sequence which hinged on the intrinsic nucleo/electrophilic reactivity of both the radicals, alkene, and alkynones, allowing β-trifluoromethyl alkyl thiochromones furnished with high efficiency and excellent functional group tolerance. By virtue of this procedure, three distinct chemical bonds including C(sp2)-C(sp3), C(sp3)-C(sp3), and C(sp2)-S have been successively forged in a single pot.

1,2‐Arylsulfonylation of Vinyl Ethers and Esters Enabled by Dual Ni Catalysis

AbstractA dual photocatalytic sulfonylation‐arylation of electron‐rich alkenes is described. By combining sulfinate salts, (hetero)‐aryl‐bromides and 2,3‐dihydrofuran under Ru and Ni dual catalysis, over 35 examples of aryl‐sulfonylated scaffolds could be obtained in good to excellent yields, under mild reaction conditions and high diastereoselectivity.

Synthesis of hyocholic acid and its derivatization with sodium periodate to distinguish it from cholic acid by mass spectrometry

Low concentrations of hyocholic acid in human serum has been linked to diabetes. Due to its important role in human health, we were interested in synthesizing hyocholic acid to explore potential biochemical properties of this bile acid. Here, a synthesis of hyocholic acid is reported from chenodeoxycholic acid. The key step was a Rubottom oxidation of a silyl enol ether intermediate to directly incorporate the oxygen at C6. Furthermore, the synthesized hyocholic acid product was treated with NaIO4 to cleave the C6-C7 bond to yield a hemiacetal at C6. This CC bond cleavage reaction using NaIO4 was used to develop an ultra-performance liquid chromatography mass spectrometry method to distinguish between a 1 to 1 mixture of hyocholic acid and cholic acid (a 12α-hydroxylated bile acid), two bile acid regioisomers with identical masses. Upon treatment of the mixture with NaIO4, hyocholic acid was selectively cleaved in the B ring (C6-C7 bond) to yield the hemiacetal that formed between the C3-hydroxy and the C6-aldehyde moiety with an m/z 405 while cholic acid remained intact with an m/z 407 in the negative electrospray ionization mode. Subsequently, a commercially available ox bile extract was treated with NaIO4 to detect bile acid derivatives by mass spectrometry. Two possible hyocholic acid derivatives conjugated to serine and gamma-glutamic semialdehyde were detected in electrospray ionization positive mode, which oxidatively cleaved with NaIO4 (m/z 496 and 522 to m/z 494 and 520, respectively).

Are (Co)Polymers of 1,1,3,3,3-Pentafluoropropene Possible?

The copolymerization and terpolymerization of 1,1,3,3,3-pentafluoropropene (PFP) with various combinations of fluorinated and hydrogenated comonomers were investigated. The chosen fluoromonomers were vinylidene fluoride (VDF), 3,3,3-trifluoropropene (TFP), hexafluoropropene (HFP), perfluoromethylvinyl ether (PMVE), chlorotrifluoroethylene (CTFE) and tert-butyl-2-trifluoromethacrylate (MAF-TBE), while the hydrocarbon comonomers were vinylene carbonate (VCA), ethyl vinyl ether (EVE) and 3-isopropenyl-α,α-dimethylbenzyl isocyanate (m-TMI). Copolymers of PFP with non-homopolymerizable monomers (HFP, PMVE and MAF-TBE) led to quite low yields, while the introduction of VDF enabled the synthesis of poly(PFP-ter-VDF-ter-M3) terpolymers with improved yields. PFP does not homopolymerize and delays the copolymerizations. All polymers were either amorphous fluoroelastomers or fluorothermoplastics with glass transition temperatures ranging from -56 °C to +59 °C, and they exhibited good thermal stability in air.

One-Pot Synthesis of Depolymerizable δ-Lactone Based Vitrimers.

A depolymerizable vitrimer that allows both reprocessability and monomer recovery by a simple and scalable one-pot two-step synthesis of vitrimers from cyclic lactones is reported. Biobased δ-valerolactone with alkyl substituents (δ-lactone) has low ceiling temperature; thus, their ring-opening-polymerized aliphatic polyesters are capable of depolymerizing back to monomers. In this work, the amorphous poly(δ-lactone) is solidified into an elastomer (i.e., δ-lactone vitrimer) by a vinyl ether cross-linker with dynamic acetal linkages, giving the merits of reprocessing and healing. Thermolysis of the bulk δ-lactone vitrimer at 200°C can recover 85-90wt% of the material, allowing reuse without losing value and achieving a successful closed-loop life cycle. It further demonstrates that the new vitrimer has excellent properties, with the potential to serve as a biobased and sustainable replacement of conventional soft elastomers for various applications such as lenses, mold materials, soft robots, and microfluidic devices.

Features of the intramolecular Hosomi–Sakurai reaction of allylic cyclopentenylsilane containing an enol ether moiety

A new intramolecular variant of the Hosomi–Sakurai reaction of 5-(2-methoxyvinyl)-4-((phenylthio)methyl)cyclopent-2-en-1-yl)trimethylsilane is presented, which is a by-process between hydrolysis to aldehyde and acetalization to dimethylacetal. The key steps are the generation of methoxy methylene carbocation from enol ether during acid catalysis and its subsequent attack on the allylsilane moiety with formation of norbornene derivative. In turn, the corresponding aldehyde undergoes Hosomi–Sakurai cyclization by interaction with BF3·Et2O in acetonitrile, as well as by reaction with TBAF in THF through various transition states, leading to epimeric alcohols of the same norbornene structure. At the same time, the starting enol ether by treatment with TBAF undergoes exclusively protodesilylation and hydrolysis, while with BF3·Et2O it gives mixtures of epimeric products of topology both bicyclo[2.2.1]heptane and bicyclo[3.2.0]heptane.

In vitro activity and mechanism of cell death induction of cyanomethyl vinyl ethers derivatives against Trypanosoma cruzi

Chagas disease causes a problematic pathology that can lead to megacolon and heart disease, and can even cause the death of the patient. Current therapies for this disease are the same as they were 50 years ago, are not fully effective and have strong side effects. The lack of a safe and effective therapy makes it necessary to search for new, less toxic and totally effective compounds against this parasite. In this work, the antichagasic activity of 46 novel cyanomethyl vinyl ether derivatives was studied. In addition, to elucidate the type of cell death that these compounds produce in parasites, several events related to programmed cell death were studied. The results highlight four more selective compounds, E63, E64, E74 and E83, which also appear to trigger programmed cell death, and are therefore postulated as good candidates to use in future therapeutics for Chagas disease.

Wax Composition of Serbian Dianthus spp. (Caryophyllaceae): Identification of New Metabolites and Chemotaxonomic Implications.

Although ethnopharmacologically renowned, wax constituents of Dianthus species were sporadically studied. A combination of GC-MS analysis, synthesis, and chemical transformations enabled the identification of 275 constituents of diethyl-ether washings of aerial parts and/or flowers of six Dianthus taxa (Dianthus carthusianorum, D. deltoides, D. giganteus subsp. banaticus, D. integer subsp. minutiflorus, D. petraeus, and D. superbus) and one Petrorhagia taxon (P. prolifera) from Serbia. Seventeen of these constituents (nonacosyl benzoate, additional 12 benzoates with anteiso-branched 1-alkanols, eicosyl tiglate, triacontane-14,16-dione, dotriacontane-14,16-dione, and tetratriacontane-16,18-dione) and two additional synthesized eicosyl esters (angelate and senecioate) represent completely new compounds. The structures of the tentatively identified β-ketones were confirmed by analysis of the mass fragmentation of the corresponding pyrazoles and silyl enol ethers obtained by transformations of crude extracts and extract fractions. Silylation allowed the identification of 114 additional constituents, including a completely new natural product (30-methylhentriacontan-1-ol). The results obtained by multivariate statistical analyses showed that the chemical profile of Dianthus taxa's surface waxes is subject to both genetic and ecological factors, whereas the latter seemingly takes a more important role for the studied Dianthus samples.

3-Alkoxyphthalides as Nonhomopolymerizable, Highly Reactive Comonomers for ABC Pseudo-Periodic Terpolymers and Degradable Polymers via Cationic Co- and Terpolymerizations with Oxiranes and/or Vinyl Ethers

3-Alkoxyphthalides (ROPTs) are promising candidate monomers that react with a cationic species at the carbonyl group and subsequently undergo ring-opening to generate a carbocation adjacent to both aryl and alkoxy groups (oxocarbenium ion). In this study, cationic polymerizations of ROPTs bearing methoxy, isopropoxy, tert-butoxy, or phenoxy groups were investigated with a particular focus on the copolymerizations with oxiranes. Cationic homopolymerization of ROPTs did not occur under any of the examined conditions. In contrast, cationic copolymerizations of ROPT with oxiranes, such as 4-vinyl-1-cyclohexene-1,2-epoxide (VCHO), proceeded smoothly via very frequent crossover reactions. The copolymers could be degraded under acidic conditions due to the cleavage of the acetal moieties generated by the crossover reactions from ROPT to VCHO. Cationic copolymerizations of ROPT with most of the examined vinyl ethers (VEs) and styrene derivatives did not proceed, likely due to inefficient crossover reactions from the vinyl monomers to ROPT. However, cationic terpolymerizations of VE, oxirane, and ROPT successfully proceeded via highly selective crossover reactions, resulting in ABC-type pseudo-periodic terpolymers under optimized conditions.

Regioselective Formal β-Allylation of Carbonyl Compounds Enabled by Cooperative Nickel and Photoredox Catalysis.

The Tsuji-Trost reaction between carbonyl compounds and allylic precursors has been widely used in the synthesis of natural products and pharmaceutical compounds. As the α-C-H bond is far more acidic than the β-C-H bond, carbonyl compounds undergo highly regioselective allylation at the α-position and their β-allylation is therefore highly challenging. This innate α-reactivity conversely hampers diversity, especially if the corresponding β-allylation product is targeted. Herein, we present a formal intermolecular β-C-C bond formation reaction of a broad range of aldehydes and ketones with different allyl electrophiles through cooperative nickel and photoredox catalysis. β-Selectivity is achieved via initial transformation of the aldehydes and ketones to their corresponding silyl enol ethers. The overall transformation features mild conditions, excellent regioselectivity, wide functional group tolerance and high reaction efficiency. The introduced facile and regioselective β-allylation of carbonyl compounds proceeding through cooperative catalysis allows the preparation of valuable building blocks that are difficult to access from aldehydes and ketones using existing methodology.

Regioselective Formal β‐Allylation of Carbonyl Compounds Enabled by Cooperative Nickel and Photoredox Catalysis

AbstractThe Tsuji–Trost reaction between carbonyl compounds and allylic precursors has been widely used in the synthesis of natural products and pharmaceutical compounds. As the α‐C−H bond is far more acidic than the β‐C−H bond, carbonyl compounds undergo highly regioselective allylation at the α‐position and their β‐allylation is therefore highly challenging. This innate α‐reactivity conversely hampers diversity, especially if the corresponding β‐allylation product is targeted. Herein, we present a formal intermolecular β‐C−C bond formation reaction of a broad range of aldehydes and ketones with different allyl electrophiles through cooperative nickel and photoredox catalysis. β‐Selectivity is achieved via initial transformation of the aldehydes and ketones to their corresponding silyl enol ethers. The overall transformation features mild conditions, excellent regioselectivity, wide functional group tolerance and high reaction efficiency. The introduced facile and regioselective β‐allylation of carbonyl compounds proceeding through cooperative catalysis allows the preparation of valuable building blocks that are difficult to access from aldehydes and ketones using existing methodology.

Sequence-Controlled Polymer Synthesis Derived from Alcohols, Cyclic Enol Ethers, and Vinyl Ethers: Selective Generation of 2-Alkoxy Cyclic Ethers Followed by Living Cationic Alternating Copolymerization by the One-Pot Process

Syntheses of sequence-controlled copolymers with controllable molecular weights and chain ends composed of alcohols, cyclic enol ethers, and vinyl ethers (VEs) were demonstrated using an approach consisting of selective monomer generation and subsequent alternating copolymerization. Acid-catalyzed additions of alcohols to 2,3-dihydrofuran or 3,4-dihydro-2H-pyran proceeded quantitatively to yield 2-alkoxy cyclic ethers (2-ACEs). Subsequent cationic alternating copolymerization of the 2-ACE and a VE proceeded successfully via concurrent ring-opening and vinyl-addition mechanisms, yielding copolymers with periodically arranged alcohol-derived side chain-containing cyclic enol ether and VE moieties in the repeating units. Complete degradation of the obtained copolymers into a single compound by alcoholysis confirmed the alternating sequences. The use of 2-propanol, (−)-menthol, and (1R)-endo-(+)-fenchyl alcohol was effective for the syntheses of well-defined polymers, whereas the use of methanol resulted in oligomers. The bulkiness of the alkoxy groups of the 2-ACEs likely contributed to the preference for propagation rather than chain transfer.

Conventional Radical and RAFT Alternating Copolymerizations of Hydroxyalkyl Vinyl Ethers and Dialkyl Maleates

Conventional Radical and RAFT Alternating Copolymerizations of Hydroxyalkyl Vinyl Ethers and Dialkyl Maleates

In Situ Polymerization on a 3D Ceramic Framework of Composite Solid Electrolytes for Room-Temperature Solid-State Batteries.

Solid-state batteries (SSBs) are ideal candidates for next-generation high-energy-density batteries in the Battery of Things era. Unfortunately, SSB application is limited by their poor ionic conductivity and electrode-electrolyte interfacial compatibility. Herein, in situ composite solid electrolytes (CSEs) are fabricated by infusing vinyl ethylene carbonate monomer into a 3D ceramic framework to address these challenges. The unique and integrated structure of CSEs generates inorganic, polymer, and continuous inorganic-polymer interphase pathways that accelerate ion transportation, as revealed by solid-state nuclear magnetic resonance (SSNMR) analysis. In addition, the mechanism and activation energy of Li+ transportation are studied and visualized by performing density functional theory calculations. Furthermore, the monomer solution can penetrate and polymerize in situ to form an excellent ionic conductor network inside the cathode structure. This concept is successfully applied to both solid-state lithium and sodium batteries. The Li|CSE|LiNi0.8 Co0.1 Mn0.1 O2 cell fabricated herein delivers a specific discharge capacity of 118.8 mAh g-1 after 230 cycles at 0.5 C and 30°C. Meanwhile, the Na|CSE|Na3 Mg0.05 V1.95 (PO4 )3 @C cell fabricated herein maintains its cycling stability over 3000 cycles at 2 C and 30°C with zero-fading. The proposed integrated strategy provides a new perspective for designing fast ionic conductor electrolytes to boost high-energy solid-state batteries.

Examining the Scope of Deriving β-Aryl Enones from Enol Silanes as Ketone Equivalents via Pd(II)-Mediated Sequential Dehydrosilylation and Arylation.

Silyl enol ethers were examined as a masked source of saturated ketones to derive β-aryl enones and their derivatives by dehydrosilylation to generate enones in situ and subsequent oxidative arylation with arylboronic acids as transmetallation coupling partners using relayed Pd(II) catalysis in one pot under base-free conditions. Oxygen was found to be an efficient and green oxidant to enable both dehydrosilylation of enol silanes and arylation. Additionally, arylation conditions can be custom-designed to take advantage of aryl halides as an alternative source of arylating agents. The preparative scope was investigated with 35 examples (up to 95% yield), and mechanistic studies implied a cationic Pd(II)-based catalytic system.

Experimental and theoretical insights into cationic polymerization of para-N,N-dimethylaminostyrene

The cationic polymerization electron-rich para-N,N-dimethylaminostyrene (DMAS) for high-molecular-weight polymer is few and highly challenging because of the ease reaction of N,N-dimethylamino group with proton or carbocation. In this contribution, three kinds of initiating systems including Lewis’s acid (BF3•OEt2), Brønsted acid (CF3SO3H, TfOH), and the carbocation system (IBVE-HCl/SnCl4, IBVE: isobutyl vinyl ether) were used in DMAS polymerization·BF3•OEt2 showed the highest efficiency for DMAS polymerization to afford high-molecular-weight poly(para-N,N-dimethylaminostyrene) (PDMAS). Copolymerizations of DMAS and 4-methoxystyrene (MOS) were unsuccessful no matter what the monomer feeding mode was, which only produced PDMAS or the blends of two homopolymers. Polymer chain-end analysis and NMR analysis of the intermediate showed that DMAS polymerizations obeyed cationic chain polymerization mechanism. Comprehensive theoretical DFT studies were performed to gain insight into the polymerization mechanism of DMAS. The chain transfer to the dimethylamino group of DMAS monomer was clearly found to be unique and curial to unexpected DMAS polymerization behavior.

Synthesis of Methylene Tetrahydrofurane‐Fused Carbohydrates

AbstractA reliable method is disclosed to introduce a fused methylene tetrahydrofuran ring into carbohydrates. The resulting bicyclic saccharides can be used as scaffolds in medicinal chemistry and drug design. In addition, the enol ether functionality serves as a handle that enables modification in biological systems via photoclick chemistry. The approach is based on the regioselective oxidation of the C‐3 hydroxy group in gluco‐configured pyranosides, followed by stereoselective indium‐mediated allylation. The ring formation is induced by an iodocyclization reaction with a neighboring hydroxy group. Subsequent dehydrohalogenation affords the desired methylene‐tetrahydrofuran‐containing carbohydrates.

Mechanistic Insight into Anion-Binding Catalytic Living Cationic Polymerization.

Exploiting non-covalent interactions to catalyze challenging ionic polymerizations is an ambitious goal but is in its infancy. We recently demonstrated non-covalent anion-binding catalysis as an effective methodology to enable living cationic polymerization (LCP) of vinyl ethers in an environmentally benign manner. Here, we further elucidate the structure-reactivity relationships of the elaborately designed seleno-cyclodiphosph(V)azanes catalysts and the roles of anion-binding interactions by a combined theoretical DFT study and experimental study. The investigation suggests that the distinct cis-cyclodiphosph(V)azane framework combined with "selenium effect" and electron-withdrawing 3,5-(CF3 )2 -Phenyl substitution pattern in catalyst enables a critical contribution to accessing excellent stability, anion affinity and solubility under polymerization conditions. Thus, the catalyst could leverage anion-binding interactions to precisely control reversible and transient dormant-active species equilibrium, allowing it to dynamically bind, recognize and pre-organize propagating ionic species and monomer, thereby facilitating efficient chain propagation and minimizing irreversible chain transfer events under mild conditions. The more in-depth understanding of the mechanism for anion-binding catalytic LCP reported herein should help to guide future catalyst design and to extend this concept to broader polymerization systems where ionic species serve as crucial intermediates.

Mechanistic Insight into Anion‐Binding Catalytic Living Cationic Polymerization

AbstractExploiting non‐covalent interactions to catalyze challenging ionic polymerizations is an ambitious goal but is in its infancy. We recently demonstrated non‐covalent anion‐binding catalysis as an effective methodology to enable living cationic polymerization (LCP) of vinyl ethers in an environmentally benign manner. Here, we further elucidate the structure‐reactivity relationships of the elaborately designed seleno‐cyclodiphosph(V)azanes catalysts and the roles of anion‐binding interactions by a combined theoretical DFT study and experimental study. The investigation suggests that the distinct cis‐cyclodiphosph(V)azane framework combined with “selenium effect” and electron‐withdrawing 3,5‐(CF3)2‐Phenyl substitution pattern in catalyst enables a critical contribution to accessing excellent stability, anion affinity and solubility under polymerization conditions. Thus, the catalyst could leverage anion‐binding interactions to precisely control reversible and transient dormant‐active species equilibrium, allowing it to dynamically bind, recognize and pre‐organize propagating ionic species and monomer, thereby facilitating efficient chain propagation and minimizing irreversible chain transfer events under mild conditions. The more in‐depth understanding of the mechanism for anion‐binding catalytic LCP reported herein should help to guide future catalyst design and to extend this concept to broader polymerization systems where ionic species serve as crucial intermediates.

Atmospheric oxidation of unsaturated hydrofluoroethers initiated by OH radicals

Hydrofluoroethers (HFEs) are perfluorinated chemicals that were developed as alternative for chlorofluorocarbons (CFCs) in various applications. Among notable unsaturated HFEs are perfluoro methyl vinyl ether (PMVE, CF3OCFCF2) and perfluoro ethyl vinyl ether (PEVE, C2F5OCF = CF2). During the implementation of PMVE and PEVE, they spill and release to the atmosphere. Due to the tendency of perfluorinated compounds to have strong infrared absorption features and long atmospheric lifetimes, they are among the most potent greenhouse gases. Thus, it is important to accurately assess their atmospheric sink routes in order to assess their impact on climate change. Herein, we illustrated detailed mechanistic pathways and developed kinetic models with the underlying aim to comprehend the atmospheric fate of the title HFEs and the likely products of decomposition. It was found that the production of main products to stem from the addition of OH radical to the inner carbon-carbon double bond atoms. Atmospheric lifetimes of PMVE and PEVE were calculated to be ∼23 and ∼56 h; respectively. Time-dependent molar yields are acquired for the experimentally major products; namely carbonyl fluoride (CF2O), perfluorinated glyoxal (CFOCFO), perfluorinated methylformates (CF3OCFO and CF3CF2OCFO). Photochemical Ozone Creation Potentials (POCPs) of PMVE and PEVE were calculated to be 1.78 and 1.18, respectively. Obtained results tap into efforts that aim to understand the atmospheric chemistry cycles of perfluorinated chemicals in general.