Cyclic Sulfonium Research Articles

Visible‐Light‐Induced Copper‐Catalyzed Alkylation/exo‐Cyclization of 1,7‐Dienes with Sulfonium Salts to Access Sulfur‐Containing Polycyclic Compounds

AbstractA direct visible‐light‐promoted radical‐triggered tandem cyclization of 1,7‐diene systems with cyclic sulfonium salts by using copper(I)‐based complexes as photoredox catalyst is developed. With this approach, a variety of sulfur‐containing polycyclic derivatives are prepared through alkylation/6‐exo‐trig cyclization/5‐exo‐trig cyclization of 1,7‐diene systems under mild conditions. In addition, the photoinduced copper‐catalyzed ring‐opening of cyclic sulfonium salts provides the alkyl radical intermediates, which prefers addition to the C−C double bond that connected to the aromatic ring rather than the electron‐deficient vinyl in 1,7‐dienes. Moreover, oxidation of the desired sulfur‐containing polycyclic products provides a strategy for the preparation of remote nitrogen‐fused polycyclic substituted sulfoxide or sulfone‐containing derivatives.

Ring-Opening Sulfonylation of Cyclic Sulfonium Salts with Sodium Sulfinates under Transition-Metal- and Additive-Free Conditions.

Incorporating a sulfonyl group into parent molecules has been shown to effectively improve their synthetic applications and bioactivities. In this study, we present a straightforward and practical approach for the ring-opening reaction of alkenyl-aryl sulfonium salts with sodium sulfinates to produce a range of sulfur-containing alkyl sulfones. This method offers the benefits of mild reaction conditions, easily accessible raw materials, wide substrate applicability, good functional group compatibility, and operational simplicity. Importantly, the resulting products can be readily converted into sulfoxides, sulfones, sulfoximines, and some heterocyclic compounds.

Bicarbonate-binding catalysis for the enantioselective desymmetrization of keto sulfonium salts

Herein, an enantioselective desymmetrization of cyclic keto sulfonium salts through enantioselective deprotonation/ring opening process by anion-binding catalysis is presented. We report a squaramide/HCO3- complex as catalytic active species which is able to stereo-differentiate two enantiomeric protons, triggering the ring opening event taking advantage of the great tendency of sulfonium salts to act as leaving groups. Thus, this desymmetrization methodology give rise to β-methylsulfenylated sulfa-Michael addition type products with excellent yields and very good enantioselectivities. The bifunctional organocatalyst has been demonstrated to be capable of activating simultaneously the base and the keto sulfonium salt by DFT calculations and experimental proofs.

Ligand-promoted reductive coupling between aryl iodides and cyclic sulfonium salts by nickel catalysis

Ligand-promoted reductive coupling between aryl iodides and cyclic sulfonium salts by nickel catalysis

Base-Promoted Ring-Opening Hydroxylation of Cyclic Sulfonium Salts.

Herein, we reported a general strategy for the synthesis of sulfur-containing primary alcohol derivatives by base-promoted ring-opening hydroxylation of cyclic sulfonium salts. A variety of sulfonium salts were successfully transformed into the desired hydroxylated products in moderate to excellent yields with good functional group tolerance. Moreover, the one-pot synthesis, scale-up reaction, and late-stage functionalization of complex molecules demonstrated the practicability of this synthetic protocol in the field of synthetic chemistry.

Synthesis, Characterization, and Evaluation of Sulfonium Lipids as Potential Nonviral Gene Vectors

Introduction: Non-viral gene vectors have attracted much attention in the last few decades because of their potential activity and fewer side effects. Headgroup chemistry is a key aspect of lipid design. Methods: In this study, a group of sulfonium lipids were designed and constructed by combining tetrahydrothiophene or tetrahydrothiopyran with an ethoxy linker and carbon aliphatic chains and were evaluated in terms of their ability as potential gene vectors. The sulfonium lipids were synthesized and characterized by 1H NMR, 13C NMR, and Mass. Condensates of sulfonium lipids (SL) and DNA were examined by gel electrophoresis and particle size and zeta potential were measured. Sulfonium compounds were tested on HepG2 cells for cytotoxicity. SL/DNA condensates were studied in cellular uptake and distribution using fluorescent microscopy. Results: 12 sulfonium lipids were obtained. Gel electrophoresis experiments showed that sulfonium cation can effectively interact with phosphorous in DNA. Compounds containing longer lipid chains can effectively retard DNA at an S/P ratio higher than 10/1 and can condense DNA into nano size particles with particle size in the range of 150 nm ~ 300 nm and zeta potential in the range of +20~+40. Sulfonium compounds were calculated against HepG2 cells in the range of 0.035 μg/mL to 1.64 μg/mL. The intracellular uptake experiments revealed that SL/DNA nanoparticle was taken into the cell at low efficiency. Conclusion: Sulfonium head group can interact with the phosphates of DNA. The structural environment of sulfonium ions influences the DNA bonding effect. The designed cyclic sulfonium ion was buried in the middle of the structure and thus hindered interaction with DNA. This type of molecule is worthy of further modification to increase DNA capacity and reduce cell cytotoxicity.

Hypervalent iodide(iii)-mediated thiofluorination of alkenes and alkynes from thioureas/thiocarbamoyl fluorides with water and a nucleophilic fluoride source

This article discloses the unprecedented hypervalent iodide(iii)-mediated thiofluorination of alkenes/alkynes involving the cyclic sulfonium ion intermediate or traditional π-complexes.

Visible light/copper catalysis enabled Heck-like coupling between alkenes and cyclic sulfonium salts via selective C–S bond cleavage

A Heck-like coupling of cyclic sulfonium salts with alkenes via selective C–S bond cleavage using a copper complex as a photosensitizer through a visible-light-driven redox-neutral process has been developed.

Synthesis of S-alkyl phosphorothioates/phosphorodithioates via ring-opening reaction of sulfonium salts with S8, H-phosphonates or P4S10, and alcohols

A simple and practical method for the synthesis of S-alkyl phosphorothioates/phosphorodithioates through the three-component reaction of cyclic sulfonium salts with S8, H-phosphonates, or P4S10, and alcohols was readily developed.

Mechanistic Insight from Lewis-Acid-Dependent Selectivity and Reversible Haloboration, as Harnessed for Boron-Based Electrophilic Cyclization Reactions.

Different reaction selectivity occurs with the Lewis acids B-chlorocatecholborane (ClBcat), B-bromocatecholborane (BrBcat), and BBr3, favoring either alkyne haloboration, electrophilic cyclization of a tethered nucleophilic sulfur onto the alkyne, or group transfer of the nucleophile. This reaction selectivity also depends on the chain length of the tethered nucleophile, revealing a subtle interplay of relative kinetics and thermodynamics. In all cases, BBr3 reacts readily with alkynes to form haloborated products; however, this process is reversible, and this reversibility can be harnessed to ultimately access regio- and stereodefined cyclic sulfonium zwitterions via the slower but thermodynamically favored electrophilic cyclization pathway. Reversibility was noted by following the reaction by NMR spectroscopy, and by characterizing the kinetic and thermodynamic products by a combination of 2D NMR spectroscopy and single-crystal X-ray diffraction. The "mixed" reagent bromocatechol borane (BrBcat) displayed reactivity between ClBcat and BBr3, producing bromoboration in some cases and electrophilic cyclization in others. With this enhanced understanding of the reaction dynamics, it becomes possible to use boron Lewis acids in a predictable manner in cases where haloboration is the kinetic product but in which the reversibility of this reaction maintains access to eventual alternative reactivity leading to desired building blocks in organic synthesis.

Effective degradation of sulfur mustard simulant using novel sulfur-doped mesoporous zinc oxide under ambient conditions

Sulfur doped metal oxides were synthesized using a two-step precipitation method. When reacted against neat 2-CEES (2-chloroethyl-ethyl sulfide, a mustard gas simulant) under ambient conditions, sulfur doped mesoporous zinc oxide (MS-Zn) showed higher catalytic activity than the other metal oxides with 92.7% overall conversion in 24 h for a 2.5 μL neat 2-CEES droplet added on top of 2 × 2 cm large 400 mg catalyst layer. The reaction proceeded mainly by hydrolysis and further solvolysis reaction also occurred depending on the extracting solvents. Cyclic sulfonium ion intermediate reaction was thought to be involved in this reaction, and metal oxide surfaces were thought to facilitate the formation of sulfonium ions from adsorbed 2-CEES. All other by-products were also found to form via sulfonium ions, reconfirming the well-known importance of this intermediate species for the degradation reaction to proceed. The sulfur content for MS-Zn was varied and tested for degradation of neat 2-CEES. This modification showed that there is an optimal amount of sulfur content for the peak catalytic activity of MS-Zn for 2-CEES degradation. Adsorption energy of a 2-CEES molecule was calculated on model sulfur doped and non doped zinc oxide surfaces and the different adsorption energy levels were correlated with the catalytic activity of sulfur doped zinc oxide.

Identification and toxicological evaluation of cyclic sulfonium ion degradation products of sulphur mustard

In the aftermath of WWII large amount seized German chemical munitions were dumped in the Baltic Sea by Allied forces. In this work, we have compared the chemical content of the solidified blocks of dumped WWII mustard gas collected from the Baltic Sea with solid precipitate from stored mustard gas, known as heel. We have identified the same cyclic sulfonium ions in both samples. In assessing the environmental and toxicological impact of dumped sulphur mustard munitions on the world's oceans the potential risk posed by cyclic sulphur mustard salts have so far not been incorporated.The toxicity of 1-(2-chloroethyl)-1,4-dithiane and its hydrolysis product 1-(2-hydroxyethyl)- 1,4-dithiane was evaluated using three different cell lines. Their effect on released pro-inflammatory cytokines was also measured. The toxicity tests showed low toxicity and low pro-inflammatory response and we therefore conclude that the environmental threat posed by these compounds is low.

Rationally designed high-performance Zr(OH)4@PAN nanofibrous membrane for self-detoxification of mustard gas simulant under an ambient condition

Self-detoxifying materials capable of destructing chemical warfare agents (CWAs) under an ambient condition is highly desirable for the next generation of personal protection. To obtain the self-detoxifying material toward mustard gas, herein, Zr(OH)4@PAN nanofibrous membrane (NFM) was designed and fabricated through an electrospinning and subsequently alkali treatment, which showed sequestration and catalytic destruction properties simultaneously toward the surrogate of mustard gas, 2-chloroethyl ethyl sulfide (CEES). Thanks to the large number and high alkalinity of the terminal hydroxyls of the present Zr(OH)4, the membrane exhibits superior self-detoxification property toward CEES (t1/2 = 0.98 h, 0.28 h at 20 °C and 40 °C, rh = 50%) at a simulative applied scenario of chemical warfare agents (CWAs), that is, the detoxification of CEES can be realized under ambient condition without any other requirements, such as the solvent, buffer solution, irradiation, oxidant, etc. Combing the sequestration effect of the porous membrane, the as-prepared Zr(OH)4@PAN NFM shows force-protection potential toward CWAs. Over 90% of CEES was transformed to non-toxic products in 4 h with Zr(OH)4@PAN NFM as the catalyst. In addition, the membrane can prevent the CEES droplets from entering, and only 0.238% of the CEES can penetrate after exposed in CEES aerosols for 3 h. The detoxification mechanism was further investigated in detail based on the experiments and the quantum mechanical studies, which revealed a multiple pathways transformation route from the toxic CEES to non-toxic HEES and EVS via cyclic sulfonium cations.

Synthesis and physical properties of new low-viscosity sulfonium ionic liquids

Several new sulfonium ionic liquids (ILs) with dicyanamide ([DCA]−) and bis(trifluoromethylsulfonyl)imide ([TFSI]−) counter anions have been synthesized. Their viscosity and ionic conductivity values were determined. The ILs with [DCA]− were previously prepared by the metathesis reaction involving silver dicyanamide (AgDCA). We report here a very convenient and much less expensive method using an ion-exchange resin. The structures of these ILs have been confirmed by 1H-NMR, 13C-NMR, and elemental analysis. Some of these sulfonium ILs displayed low viscosity ( 10 mS cm−1). A concluding remark on structure-property relationship has also been drawn involving alicyclic and cyclic sulfonium cations vs. [DCA]− and [TFSI]− anions.

Recent advance in sulfur ylide and sulfonium salts chemistry

Organosulfur compounds are ubiquitous in natural products and active pharmaceutical ingredients. They are also versatile scaffold that are widely applicable in material and food chemistry. The increasing demand indeed lead to a continuous progress in developing of new methodologies in organosulfur chemistry. Among them, sulfur ylides and sulfonium salts with unique reactivities have been employed to provide simple, effective, and often stereoselective methods to gain access to sulfur containing molecules. The essential goal of this review is to provide a comprehensive account of representative research progress on sulfonium salt and sulfur ylide chemistry in the past three years. Seminal reports on this topic are occasionally covered with the purpose of providing a brief research background. For the sake of convenience, this review is organized in three parts based on the role they played in organic reactions (synthetic intermediates, reagents and catalysts). In the first section, the development of new approaches for generate sulfur ylide or sulfonium salt intermediates were summarized. Electrophilic aryne species could be employed to react with sulfides or sulfoxides to form the desired sulfur intermediates, which could underwent a variety of interesting transformations. Moreover, recent progress in metal carbene-based sulfur ylide approaches have also been introduced. Both the progress in asymmetric catalysis variants and reactions in aqueous solution have been presented. The second section describes the transformations using stabilized sulfonium salts and sulfur ylides as bench-stable reactants. The extra stability of these species is accompanied by a compromise in the reactivity, which usually requires developing activation methods. With transition metal catalysts to activate sulfonium salts, they have been discovered as efficient coupling partners in carbon-carbon bond and carbon-heteroatom bond formation reactions. Stable sulfur ylides could also be utilized to install fluorine-containing groups in a large variety of transformations. The third section covers recent progress in employing sulfonium salts as catalysts in organic reactions. The acidity of the α C−H in sulfonium salt is relatively high than its nitrogen and phosphine analogues. Therefore, it could be easily removed to form the sulfur ylide, which have restricted its application as catalysts. On one hand, scientists took advantage of these properties and developed new cyclic sulfonium salts as hydrogen bonding catalysts. On the other hand, sulfonium salts could be used as stable phase transfer catalysts under base free conditions in order to avoid degradations. Finally, the review discussed the limitations of the known chemistry in this field as well as the future opportunities. Sulfur ylide and sulfonium salts have displayed many unique reactivities as summarized in this review. New reactivity will still be the central theme of research given the importance of organosulfur compounds. In addition, insights into the factors controlling the reactivity via mechanistic studies will be of great importance for further research and development. Moreover, the applications of sulfonium salts as organocatalysts are still limited to a relatively narrow range of transformations. Therefore, it remains to be an elusive task to unlock their full potential, and future research must include the development of scalable and cost-efficient methods, broadening of reaction scopes, and integration with other catalytic manifolds. We hope that this review will pique the interests of readers and deliver inspiration for future development in this interesting and promising field.

Acyclic and Cyclic Alkyl and Ether-Functionalised Sulfonium Ionic Liquids Based on the [TFSI]- and [FSI]- Anions as Potential Electrolytes for Electrochemical Applications.

This work provides a study based on acyclic and cyclic sulfonium ionic liquids (ILs) with alkyl and ether-functionality on the cation paired with the bis{(trifluoromethyl)sulfonyl}imide, [TFSI]- , or the bis(fluorosulfonyl)imide, [FSI]- , as the counter anion. Herein, thermophysical characterisation of nine sulfonium-based ILs concerning the density, viscosity and conductivity and thermal properties including phase transition behaviour and decomposition temperature is reported. The electrochemical stability of the ILs was also measured by cyclic voltammetry at a glassy carbon macro-disk electrode. All of the ILs showed low melting point, low viscosity and good conductivity and could serve as potential electrolytes for energy storage devices.

Delayed gelation kinetics of hydrogel formation by ionic nano-gel cross-linkers

In our previous work, linear polyelectrolyte cross-linker-bridged hydrogel showed fast gelation within hours, which constrained in-depth deployment of such gels. In the present report, precipitation polymerization of bifunctional VBCTHt monomers in ethanol and acetonitrile generated the nano-gel cross-linkers bearing cyclic sulfonium moieties. The addition of nano-gels cross-linkers to partially hydrolyzed poly(acrylamide) formed covalently cross-linked in situ gels at the temperatures greater than 25 °C. As the morphology of the cross-linker changed from linear form to nano-gel in the state of sphere, the gelation time was controlled from 3 to 40 h. Nano-gel–HPAM system showed three orders of magnitude of delayed gelation while maintaining comparable mechanical integrity in comparison with conventional metallic cross-linked in situ gel, where sulfonium-functionalized nano-gel cross-linkers acting as covalent gelator were utilized for in situ gel formation. The change in cross-linker morphology and bonding nature of the gels dramatically extended gelation time. The mechanics of nano-gel cross-linker-derived covalently cross-linked HPAM in situ gels could be tuned by nano-gel cross-linkers concentration. The viscosity of HPAM and ionic cross-linker gelant had lower viscosity compared to conventional Cr3+–HPAM gel system as confirmed by rheological measurements. The gelant showed excellent salt and pH resistance, rendering it applicable to reservoir conditions. We believe this pioneer work in examination of cross-linker morphology to dictate hydrogel gelation offered the possibility to deploy mechanically tunable gels with delayed gelation for in-depth treatment of reservoir formation to improve fossil energy recovery.

Barium titanate perovskite nanoparticles as a photoreactive medium for chemical warfare agent detoxification

Barium titanate nanoparticles (BTO-NPs) in the size range 8–12 nm, prepared by gel collection, are found to be a photoreactive detoxifier for Chemical Warfare Agent vapors, specifically, the sulfur mustard surrogate (2-chloroethyl ethyl sulfide). The relatively monodisperse, uniformly spherical BTO-NPs, initially dispersed in alcohol solvents, form a stable and porous aggregated structure reminiscent of a nanostructured material with voids/pores of an average diameter of 4.6 nm and a relatively narrow distribution of their sizes (2.5–8.7 nm). Due to the interparticle porosity and a polar, chemically active surface, signifcant amounts of CWA surrogate and its decomposition products were adsorbed on the BTO-NPs. The recorded weight uptake on the perovskite was the highest among a series of materials and nanocomposites known for their detoxification activity and tested at the same conditions (169 mg/g, compared to 117 mg/g for zinc oxide and <100 mg/g for other transition metal oxides). Besides adsorption, BTO nanomaterial acts simultaneously as an efficient heterogeneous catalyst by degrading the toxic vapors to alcohols, sulfides and thiols – molecules of significantly lower toxicity than the CWA surrogate. Hydrolysis and dehydrohalogenation were the predominant detoxification pathways, via the formation of the intermediate cyclic sulfonium, whether under light or in the dark. Ambient light irradiation promoted the photo-oxidation and photo-degradation by radical intermediates formed. With an unhindered oxygen rich surface, underlying highly polarizable lattice structure, and large accessible surface area, barium titanate nanoparticles are investigated as a potentially useful medium for photoreactive detoxification of chemical warfare agent vapors.

Low temperature applicable polyelectrolyte gelator to covalently bridged partially hydrolyzed poly(acrylamide) in situ gel for fossil energy recovery

Low temperature applicable cyclic sulfonium functionalized poly(vinylbenzyl chloride) (PVBC) electrolyte gelator for partially hydrolyzed poly(acrylamide) (HPAM) in situ gel is described herein. Addition of polyelectrolyte gelator to HPAM generated covalently crosslinked in situ gels through formation of ester crosslinks under reservoir conditions. The generation of covalent crosslinks through chemically nucleophilic attack by carboxylate groups tethered to HPAM backbone to sulfonium moieties was demonstrated by corresponding spectra analysis of nuclear magnetic resonance (NMR) and rheological studies. Compared to high temperature phenol/formaldehyde and poly(ethyleneimine) gelator system, the gelation of PVBCTHt polyelectrolyte gelator and HPAM occurred over a broad range of temperatures from 25 to 80 °C. At 25 °C the gelation of PVBCTHt gelator and HPAM was significantly delayed to weeks compared to Cr3+-HPAM system having fast gelation kinetics in 6 h. Due to its delayed gel formation over weeks at room temperature, the gel could be deployed for in-depth reservoir treatment. The gelant showed excellent salt and pH resistance under reservoir conditions as reflected by mechanical integrity of in situ bulk gel. Core flooding experiment on sandpack demonstrated the gel could efficiently divert brine flow for conformance control, which displayed better plugging efficiency than Cr3+-HPAM system.

An ether-functionalised cyclic sulfonium based ionic liquid as an electrolyte for electrochemical double layer capacitors

A novel cyclic sulfonium cation-based ionic liquid (IL) with an ether-group appendage and the bis{(trifluoromethyl)sulfonyl}imide anion was synthesised and developed for electrochemical double layer capacitor (EDLC) testing. The synthesis and chemical-physical characterisation of the ether-group containing IL is reported in parallel with a similarly sized alkyl-functionalised sulfonium IL. Results of the chemical-physical measurements demonstrate how important transport properties, i.e. viscosity and conductivity, can be promoted through the introduction of the ether-functionality without impeding thermal, chemical or electrochemical stability of the IL. Although the apparent transport properties are improved relative to the alkyl-functionalised analogue, the ether-functionalised sulfonium cation-based IL exhibits moderately high viscosity, and poorer conductivity, when compared to traditional EDLC electrolytes based on organic solvents (propylene carbonate and acetonitrile). Electrochemical testing of the ether-functionalised sulfonium IL was conducted using activated carbon composite electrodes to inspect the performance of the IL as a solvent-free electrolyte for EDLC application. Good cycling stability was achieved over the studied range and the performance was comparable to other solvent-free, IL-based EDLC systems. Nevertheless, limitations of the attainable performance are primarily the result of sluggish transport properties and a restricted operative voltage of the IL, thus highlighting key aspects of this field which require further attention.