Vinyl Sulfones Research Articles

Trifluoromethylated Oxidopyridinium Betaines: Unique (5+2) Cycloaddition Selectivity Imposed by 2- or 6-Trifluoromethyl Groups.

Despite the significant advances in trifluoromethylation methods, the synthesis of complex trifluoromethylated molecules, bearing a natural-product-like three-dimensional framework, remains as a formidable challenge. Therefore, the cycloaddition of unprecedented CF3 -substituted oxidopyridinium betaines was investigated. After the methylation of trifluoromethylated pyridin-3-ols with methyl triflate, pyridinium ions generated in-situ were treated with triethylamine in the presence of N-methylmaleimide to produce trifluoromethylated 8-azabicyclo[3.2.1]octane derivatives via (5+2) cycloaddition of the corresponding oxidopyridinium betaines. Exo/endo-selectivity varied depending on the positions of the CF3 substituents; endo-products were preferred in the reactions of oxidopyridinium betaines with the CF3 group at the 2- or 6-positions, whereas the 5-CF3 -substituted betaine exclusively produced an exo-product. Moreover, unique regio- and stereoselectivities have been observed in the reactions of 2- or 6-CF3 -substituted oxidopyridinium betaines with vinyl sulfones and trans-1,2-disubstituted alkenes. To gain insight into the reactivity of trifluoromethylated oxidopyridinium betaines, computational investigations were also conducted.

Mn(OAc)3-Mediated Unexpected Cycloannulative Sulfonyl Migration Cascade using (E)-β-Iodovinyl Sulfones and ortho-Alkynylphenols for Direct Synthesis of Chromene-Derived Vinyl Sulfones.

Cycloannulative sulfonyl migration has received much attention; however, a carbon-to-carbon sulfonyl group shift still needs to be discovered. We hereby report a base-mediated oxa-Michael addition-elimination of (E)-β-iodovinyl sulfones with ortho-alkynylphenols, followed by cycloisomerization and unique stereoselective sulfonyl migration in one-pot, is realized under the influence of Mn(OAc)3·2H2O. A broad range of vinyl sulfone-tethered chromenes were readily accessed in moderate to high yields with good functional group compatibility. Notably, the reaction was robust at the gram scale, and postsynthetic transformations were successfully uncovered. Moreover, plausible mechanistic pathways were rationalized on the basis of existing experimental results.

Catalyst- and Base-Free Synthesis of Morita-Baylis-Hillman and Rauhut-Currier Adducts of β-Aminonitroalkenes.

A facile, base- and catalyst-free synthesis of Morita-Baylis-Hillman and Rauhut-Currier adducts of β-aminonitroalkenes with different electrophiles such as ethyl glyoxylate, trifluoropyruvate, ninhydrin, vinyl sulfone, and N-tosylazadiene is reported. The products are formed in good to excellent yields at room temperature with a broad substrate scope. The adducts of ninhydrin and β-aminonitroalkene spontaneously cyclize to fused indenopyrroles. Gram-scale reactions and synthetic transformations of the adducts are also reported here.

Mitigating the risk of antimalarial resistance via covalent dual-subunit inhibition of the Plasmodium proteasome

The Plasmodium falciparum proteasome constitutes a promising antimalarial target, with multiple chemotypes potently and selectively inhibiting parasite proliferation and synergizing with the first-line artemisinin drugs, including against artemisinin-resistant parasites. We compared resistance profiles of vinyl sulfone, epoxyketone, macrocyclic peptide, and asparagine ethylenediamine inhibitors and report that the vinyl sulfones were potent even against mutant parasites resistant to other proteasome inhibitors and did not readily select for resistance, particularly WLL that displays covalent and irreversible binding to the catalytic β2 and β5 proteasome subunits. We also observed instances of collateral hypersensitivity, whereby resistance to one inhibitor could sensitize parasites to distinct chemotypes. Proteasome selectivity was confirmed using CRISPR/Cas9-edited mutant and conditional knockdown parasites. Molecular modeling of proteasome mutations suggested spatial contraction of the β5 P1 binding pocket, compromising compound binding. Dual targeting of P.falciparum proteasome subunits using covalent inhibitors provides a potential strategy for restoring artemisinin activity and combating the spread of drug-resistant malaria.

Asymmetric synthesis of aryl-substituted pyrrolidines by using CFAM ligand-AgOAc chiral system via 1,3-dipolar cycloaddition reaction.

We have prepared a ligand library based on a ferrocenyl aziridinyl methanol core unit (simply called FAM) having a phenyl group, a cyclohexyl group, and a naphthyl group to be used in 1,3-dipolar cycloaddition (1,3-DC) reactions for the synthesis of chiral pyrrolidines. These chiral ligands were used with AgOAc in 1,3-DC reactions taking place between the aryl-substituted azomethine ylides and N-methylmaleimide as the dipolarophile. In each case, the expected aryl-substituted pyrrolidines were obtained in good to excellent yields with acceptable enantioselectivities favoring only the endo product. The chiral catalyst system CFAM4-AgOAc was also used in 1,3-DC reaction with different dipolarophiles such as dimethyl maleate, tert-butyl acrylate, methyl acrylate, trans-chalcone, and vinyl sulfone. In each case, the cycloadducts were obtained in acceptable yields albeit with low ee. Fortunately, it was possible to increase the ee up to >99% upon crystallization.

Short wet-steaming low-carbon cleaner pad dyeing of cotton/polyamide/lyocell fabric with reactive dyes

Cotton/polyamide/lyocell three-component fabrics are usually dyed by the traditional dip dyeing technology with two kinds of dyes, which has the disadvantages of long process, high energy consumption and high cost. In this research, the short process cleaner pad dyeing technology for cotton/polyamide/lyocell fabric was developed. The optimal dyeing conditions were that the pH value of initial dye solution was 3–4, the reactive red 195 dye concentration was 10 g/L in the preliminary dye bath, the concentration of NaOH and Na2CO3 were 10 g/L in the alkaline fixing solution, and the steaming time of acid solution and alkali solution was 4 mins. The dyeing effects and fixation rate indicated that short wet-steaming technology was the optimum method. The developed short wet-steaming low-carbon cleaner pad dyeing technology of cotton/polyamide/lyocell fabric not only ensured the color yield, reproducibility, dyeing uniformity and permeability, but also saved dyes and chemicals, shortened dyeing time by 17.4 %, reduced power and heat consumption by 27.1 % and 15.1 %, and decreased carbon emission by 24.6 % compared with traditional dyeing. The K/S values of the dyed samples by short wet-steaming pad dyeing technique indicated that bifunctional reactive dyes with monochlorotriazine and vinyl sulfone sulfate groups (M-type) were superior to the other three kinds of reactive dyes. In the era of low-carbon economy, short wet-steaming low-carbon cleaner pad dyeing of cotton/polyamide/lyocell fabric with reactive dyes is an advanced short process dyeing technology worth of promotion for dyeing a variety of industrial crops and products.

A Smart MMP13‐Responsive Injectable Hydrogel with Inflammatory Diagnostic Logic and Multiphase Therapeutic Ability to Orchestrate Cartilage Regeneration

AbstractDespite numerous attempts to engineer cartilage tissue in recent years, significant challenges remain regarding hyaline cartilage regeneration. One main reason is that the overactivated inflammatory response after injury suppresses inherent cartilage regenerative capabilities. Since the arthritic microenvironment is constantly changing during posttraumatic stress, an inflammatory diagnostic logic‐based hydrogel for cartilage regeneration is developed for the first time through cross‐linking of 4‐arm poly(ethylene glycol)‐vinyl sulfone (PEG‐VS) and specific matrix metalloproteinase (MMP) 13‐sensitive peptides. The hydrogel exhibits diagnostic logic to identify the pathological cue MMP13 and accordingly determine drug release kinetics in an inflammatory microenvironment. Additionally, multiphase therapeutic ability is designed to program different cargo release behaviors to match the inflammation‐chondrogenesis cascade for better cartilage regeneration. Here, it is first proposed that MMP13 is a suitable diagnostic biomarker to modulate the inflammatory microenvironment in the early stage of cartilage injury. In vitro and in vivo studies show that the hydrogel has good injectability, on‐demand anti‐inflammation, and immunomodulation capabilities. Ultimately, loaded with multiple therapeutic factors, the hydrogel shows both microenvironmental modulation and chondrogenesis therapeutic ability, resulting in satisfactory hyaline cartilage regeneration. This study provides critical insight into the design and biological mechanism of both diagnostic and therapeutic ability‐based cartilage tissue engineering strategies.

Organocatalytic Asymmetric Morita-Baylis-Hillman Reaction of Isatins with Vinyl Sulfones.

The organocatalytic asymmetric Morita-Baylis-Hillman (MBH) reaction of isatin derivatives with various vinyl sulfones is disclosed. Chiral sulfone-containing 3-hydroxyoxindoles were produced in good to high yields and with good to high ee's. This report displays an unprecedented example to apply activated alkenes with sulfone moiety other than carbonyl groups in asymmetric MBH reactions and provides an efficient strategy to incorporate the sulfone functional group for the synthesis of chiral 3-hydroxyoxindoles.

Evaluation of Polyelectrolyte Complex Nanoparticles for Prolonged Scale Inhibitor Release in Porous Media

The formation of inorganic scales on the surfaces of porous media, production wells, and pipelines can substantially reduce the efficiency of oil production and damage reservoir formations. Scale inhibitors (SIs) are often applied to prevent or mitigate scale formation using a “squeeze treatment”, where the SI is injected into a formation and allowed to equilibrate, and then the flow is reversed (return phase). Although organic polymers, such as poly(vinyl sulfonic acid) (PVS), can tolerate high temperatures and have been effective for scale control, repeated applications may be required because they exhibit weak adsorption (retention) in most reservoir formations. To address this limitation, the release performance of a polyelectrolyte complex nanoparticle (PECNP) loaded with PVS was evaluated in laboratory-scale squeeze tests and compared to PVS alone. After injection of the PECNP into a Berea sandstone core and a 24 h shut-in period, a brine solution was introduced to the core. Following injection, the free or “active” PVS concentration in the effluent spiked to approximately 600 mg/L, decreased to 10 mg/L after 10 pore volumes (PVs), and then gradually declined to concentrations between 1 and 3 mg/L over the remaining 450 PVs of the test. Minimal PECNPs were detected in effluent samples during the return phase, indicating that PECNP attachment was irreversible under these experimental conditions. In contrast, the PVS-only squeeze test exhibited elevated PVS concentrations that approached the applied concentration immediately after a brine solution was introduced during the return phase, and the PVS return concentration decreased to below the detection limit (0.5 mg/L) after only 70 PVs. A mathematical model that incorporated nanoparticle attachment and rate-limited release of the SI successfully reproduced the experimental results and can be used to predict PECNP squeeze lifetime. These findings demonstrate the potential application of PECNPs for scale control in reservoir formations.

Cyclodextrin-Calcium Carbonate Micro- to Nano-Particles: Targeting Vaterite Form and Hydrophobic Drug Loading/Release

Tailor-made and designed micro- and nanocarriers can bring significant benefits over their traditional macroscopic counterparts in drug delivery applications. For the successful loading and subsequent release of bioactive compounds, carriers should present a high loading capacity, trigger release mechanisms, biodegradability and biocompatibility. Hydrophobic drug molecules can accumulate in fat tissues, resulting in drawbacks for the patient's recovery. To address these issues, we propose to combine the advantageous features of both host molecules (cyclodextrin) and calcium carbonate (CaCO3) particles in order to load hydrophobic chemicals. Herein, hybrid cyclodextrin-CaCO3 micro- to nano-particles have been fabricated by combining Na2CO3 solution and CaCl2 solution in the presence of an additive, namely poly (vinylsulfonic acid) (PVSA) or glycerol (gly). By investigating experimental parameters and keeping the Na2CO3 and CaCl2 concentrations constant (0.33 M), we have evidenced that the PVSA or gly concentration and mixing time have a direct impact on the final cyclodextrine-CaCO3 particle size. Indeed, by increasing the concentration of PVSA (5 mM to 30 mM) or gly (0.7 mM to 4 mM) or the reaction time (from 10 min to 4 h), particles with a size of 200 nm could be reached. Interestingly, the vaterite or calcite form could also be selected, according to the experimental conditions. We hypothesised that the incorporation of PVSA or gly into the precipitation reaction might reduce the nucleation rate by sequestering Ca2+. The obtained particles have been found to keep their crystal structure and surface charge after storage in aqueous media for at least 6 months. In the context of improving the therapeutic benefit of hydrophobic drugs, the developed particles were used to load the hydrophobic drug tocopherol acetate. The resulting particles are biocompatible and highly stable in a physiological environment (pH 7.4, 0.15 M NaCl). A selective release of the cargo is observed in acidic media (pH lower than 5).

Ion Pair Catalyst - Pentanidinium.

In this account, we further describe our already developed N-sp2 hybrid guanidinium as an efficient phase-transfer catalyst and ion pair catalysis based on N-sp2 hybrid pentanidinium and its application in some new reactions. The sp3 hybrid quaternary ammonium salt has a tetrahedral structure, which means that three sides of it can be effectively steric, allowing the remaining side to be close to the substrate. However, the sp2 hybrid ammonium salt allows the substrate to form ion pairs from both directions respectively, so it is a greater challenge to control the stereoselectivity of the reaction. Van der Waals forces, such as hydrogen bonds and interactions, have been used to make electrophiles approach from a certain direction, leading to a higher enantioselectivity. Based on the above idea, we designed an N-sp2 hybrid phase-transfer catalyst, pentanidinium. Pentanidinium has five conjugated nitrogen atoms, one of which has a formal positive charge, which is necessary for it to become an ion pair catalyst. We have confirmed that pentanidinium can catalyze α-hydroxylation of 3-substituted-2-oxindoles, Michael addition of 3-alkyloxindoles with vinyl sulfone, and alkylation reactions of sulfenate anions and dihydrocoumarins, desymmetrization of pro-chiral sulfinate to afford enantioenriched sulfinate esters. Pentanidinium with side chain structure changes can also be catalyzed efficiently with enantioconvergent halogenophilic nucleophilic substitution, including azidation and thioesterification. In the reaction catalyzed by pentanidinium, it always attracts us with the advantages of low catalytic load and good enantioselectivity.

Fluorinated Vinyl Sulfonium Salts and Their Synthetic Utilization.

The fluorinated building block strategy and the direct fluorination strategy are of great importance for the synthesis of new fluorinated molecules. These strategies complement each other and can be combined to develop a new methodology for the construction of a wide variety of fascinating organofluorine compounds. In our opinion, the versatile building blocks used in this method should satisfy the following conditions: 1) readily prepared from commercially available reagents; 2) easy to handle; 3) storage under ordinary conditions without noticeable decomposition; 4) wide applicability. Based on the aforementioned requirements, we focused on the use of vinyl sulfonium salts. This brief review describes the synthesis of five types of fluorinated vinyl sulfonium salts and their reactions. Especially, we featured typical fluorinated groups containing trifluoromethyl (CF3 ), difluoromethyl (CF2 H), monofluoromethyl (CFH2 ), monofluoro (F) or β-bromotetrafluoroethyl (BrCF2 CF2 ) moieties in combination with vinyl sulfonium salts.

Vinyl Sulfone-functionalized Acetalated Dextran Microparticles as a Subunit Broadly Acting Influenza Vaccine.

Influenza is a global health concern with millions of infections occurring yearly. Seasonal flu vaccines are one way to combat this virus; however, they are poorly protective against influenza as the virus is constantly mutating, particularly at the immunodominant hemagglutinin (HA) head group. A more broadly acting approach involves Computationally Optimized Broadly Reactive Antigen (COBRA). COBRA HA generates a broad immune response that is capable of protecting against mutating strains. Unfortunately, protein-based vaccines are often weekly immunogenic, so to help boost the immune response, we employed the use of acetalated dextran (Ace-DEX) microparticles (MPs) two ways: one to conjugate COBRA HA to the surface and a second to encapsulate cGAMP. To conjugate the COBRA HA to the surface of the Ace-DEX MPs, a poly(L-lactide)-polyethylene glycol co-polymer with a vinyl sulfone terminal group (PLLA-PEG-VS) was used. MPs encapsulating the STING agonist cGAMP were co-delivered with the antigen to form a broadly active influenza vaccine. This vaccine approach was evaluated in vivo with a prime-boost-boost vaccination schedule and illustrated generation of a humoral and cellular response that could protect against a lethal challenge of A/California/07/2009 in BALB/c mice.

Polarity Transduction Enables the Formal Electronically Mismatched Radical Addition to Alkenes.

The formation of carbon-carbon bonds via the intermolecular addition of alkyl radicals to alkenes is a cornerstone of organic chemistry and plays a central role in synthesis. However, unless specific electrophilic radicals are involved, polarity matching requirements restrict the alkene component to be electron deficient. This limits the scope of a fundamentally important carbon-carbon bond forming process that could otherwise be more universally applied. Herein, we introduce a polarity transduction strategy that formally overcomes this electronic limitation. Vinyl sulfonium ions are demonstrated to react with carbon-centered radicals, giving adducts that undergo in situ or sequential nucleophilic displacement to provide products that would be inaccessible via traditional methods. The broad generality of this strategy is demonstrated through the derivatization of unmodified complex bioactive molecules.

Electrolyte regulating and interface engineering for high voltage LiCoO2 lithium metal batteries

To achieve higher energy density of lithium ion batteries (LIBs), researchers are developing a new generation of high-voltage (≥4.5 V) LiCoO2 (LCO). Increasing the voltage is accompanied by the decomposition of the electrolyte, successive irreversible phase transitions, and dissolution of transition metals, etc., which are largely benefit from detrimental cathode-electrolyte interface reactions. Here, we construct a stable N, S-rich electrode/electrolyte interphase on both Li anode as well as LCO cathode to solve the above problems through the electrolyte design with the dual additives of acrylonitrile and phenyl vinyl sulfone. Specifically, the uniform N, S-rich cathode/electrolyte interphase (CEI) separates the electrolyte and LCO, and reduces the catalytic decomposition of the electrolyte by Co4+. Moreover, phenyl vinyl sulfone has an excellent compatibility with the Li metal anode due to the in-situ formed LiF-rich solid electrolyte interphase (SEI). With the modification of dual-additives, the LCO lithium metal battery exhibits high-capacity retention about 80 % over 1000 cycles at upper cut-off voltage of 4.5 V and 76 % over 300 cycles at 4.6 V.

Rigidified Bis(sulfonyl)ethylenes as Effective Michael Acceptors for Asymmetric Catalysis: Application to the Enantioselective Synthesis of Quaternary Hydantoins.

The catalytic, enantio- and diastereoselective addition of hydantoin surrogates II to "rigidified" vinylidene bis(sulfone) reagents is developed, thus overcoming the inability of commonly employed β-substituted vinylic sulfones to react. Adducts are transformed in enantioenriched 5,5-disubstituted hydantoins through hydrolysis and reductive desulfonylation processes providing new structures for eventual bioassays. Density functional theory studies that rationalize the observed reactivity and stereoselectivity trends are also provided.

TBADT‐Mediated C‐C Bond Formation Exploiting Aryl Aldehydes in a Photochemical Flow Reactor

AbstractA robust and general photochemical process is reported converting various aryl aldehydes into β‐ketonitriles and related species. Tetrabutylammonium decatungstate (TBADT) is used as photocatalyst in combination with a high‐power LED emitting at 365 nm. Standardization and scalability are enabled by using a flow reactor platform integrating the LED light source placed within an encased reactor coil. Under optimized conditions a variety of aromatic and heteroaromatic aldehydes is reacted with acrylonitrile, methyl methacrylate and phenyl vinyl sulfone to give the desired products in high yields, short residence times of 5–30 minutes and a throughput of up to 41 mmol/h. This continuous process overcomes limitations previously encountered for aromatic substrates and represents an effective means to generate a variety of difunctionalized building blocks for further elaborations with an ideal atom economy.

An efficient strategy based on polyelectrolyte of constructing a sequential energy transfer artificial light-harvesting system for photocatalysis

In this work, an efficient artificial light-harvesting system with a two-step sequential energy transfer process was first constructed based on the polyelectrolyte material sodium carboxymethyl cellulose (CMC) and AIE molecule cyano-substituted amphiphilic hydroquinone derivative (PPTA) in an aqueous solution. The energy harvested by the two fluorescent dyes EY and SR101 from the supramolecular assembly PPTA-CMC was fully used for photochemical catalysis for the dehalogenation of α-bromoacetophenone, cross dehydrogenation coupling reaction (CDC), and alkylation of C–H bonds of phenyl vinyl sulfone (PVS) and tetrahydrofuran (THF) in the aqueous medium.

Heterofunctional Methacrylate Beads Bearing Octadecyl and Vinyl Sulfone Groups: Tricks to Obtain an Interfacially Activated Lipase from Thermomyces lanuginosus and Covalently Attached to the Support

Lipase from Thermomyces lanuginosus (TLL) has been immobilized on a methacrylate macroporous resin coated with octadecyl groups (Purolite Lifetech®® ECR8806F). This immobilization protocol gave a biocatalyst with significantly higher stability than that obtained using octyl agarose. To further improve the biocatalyst features, we tried to covalently immobilize the enzyme using this support. For this purpose, the support was activated with divinyl sulfone. The results showed that at least 1/3 of the immobilized enzyme molecules were not covalently immobilized. To solve the problem, we produced an aminated support and then activated it with divinyl sulfone. This permitted the full covalent immobilization of the previously immobilized TLL. The use of different blocking agents as the reaction endpoint (using ethylenediamine, Asp, Gly, and Cys) greatly altered the biocatalyst functional features (activity, specificity, or stability). For example, the blocking with ethylenediamine increased the ratio of the activity versus R- and S-methyl mandelate by a three-fold factor. The blocking with Cys produced the most stable biocatalyst, maintaining close to 90% of the activity under conditions where the just adsorbed enzyme maintained less than 55%. That way, this strategy to modify the support has permitted obtaining an enzyme interfacially activated versus the octadecyl layer and, later, covalently immobilized by reaction with the vinyl sulfone groups.

Regio- and stereoselective manganese-catalyzed hydrosulfonylation of alkynes: facile access to Z-vinyl sulfones

We have reported a concise and complementary approach for the synthesis of high-selectivity (Z)-vinyl sulfones via a ligand-tuned metalloradical reactivity strategy.