Vinyl Sulfonyl Research Articles

Discovery of A Synthetic Hub for Regio- and Stereoselective Construction of Triazolyl Vinyl Sulfonyl Fluorides.

A new sulfonyl fluoride reagent 1-bromobut-3-ene-1,3-disulfonyl difluoride (BEDF) was developed. This unique reagent possesses two clickable functionalities to be used for both azide-alkyne cycloaddition click and SuFEx click reactions. This new reagent was applied for the regioselective construction of a class of novel triazolyl vinyl sulfonyl fluorides in which the C-4 position 1H-1,2,3-triazoles were functionalized with vinyl sulfonyl fluorides of exclusively E-configuration.

Stereo- and Regioselective Installation of Vinyl Sulfonyl Fluoride onto Indoles without Transition-Metal Catalyst.

Herein, we developed a practical method for synthesizing a class of novel and highly valuable indolyl vinyl sulfonyl fluorides. This protocol has carved out a path for constructing a broad range of vinyl sulfonyl fluorinated indoles with exclusive stereo- and regioselectivity through the Friedel-Crafts/elimination reaction without any transition-metal catalyst. This transformation features mild conditions, high efficiency, excellent selectivity, and rich substrate compatibility, highlighting its significant value in medicinal chemistry and many related disciplines.

A portal to highly valuable indole-functionalized vinyl sulfonyl fluorides and allylic sulfonyl fluorides.

A practical and efficient method for the C-3 site selective alkenylation of indoles was developed for constructing novel indole-functionalized vinyl sulfonyl fluorides and indolyl allylic sulfonyl fluorides. The reaction is accomplished with exclusive regio- and stereoselectivity without using transition metal catalysts, providing novel products of great potential value in medicinal chemistry, chemical biology, and drug discovery.

Stereoselective Fluorosulfonylation of Vinylboronic Acids for (E)-Vinyl Sulfonyl Fluorides with Copper Participation.

A practical synthetic method for the synthesis of vinyl sulfonyl fluorides through copper-promoted direct fluorosulfonylation has been developed. The reaction of the vinylboronic acids with DABSO and then NFSI is performed under mild reaction conditions. This transformation efficiently affords aryl or alkyl vinyl sulfonyl fluorides with good reaction yields, exclusive E-configuration, broad substrate scope, excellent compatibility, and operational simplicity.

The construction of novel pyrrole-4H-chromene-embedded vinyl sulfonyl fluorides via a three-component process

A synthetic strategy involving salicylaldehyde, 2-chloroprop-2-ene-1-sulfonyl fluoride (CESF), and pyrrole has been developed to construct novel pyrrole-4H-chromene-embedded vinyl sulfonyl fluoride derivatives with exclusive regioselectivity.

Highly compressible and macro-porous hydrogels via the synergy of cryogelation and double-network for efficient removal of Cr(VI)

Mechanically robust and macro-porous hydrogels are urgently required for the dynamic removal of heavy metals in wastewater purification field. Herein, a novel microfibrillated cellulose/polyethyleneimine hydrogel (MFC/PEI-CD) with high compressibility and macro-porous structures was fabricated via the synergy of cryogelation and double-network for Cr(VI) adsorption from wastewater. MFCs were pre-cross-linked by bis(vinyl sulfonyl)methane (BVSM) and then formed double-network hydrogels with PEIs and glutaraldehyde below freezing. The SEM showed that the MFC/PEI-CD possessed interconnected macropores with an average pore diameter of 52 μm. Mechanical tests indicated a high compressive stress of 116.4 kPa at 80 % strain, which was 4 times higher than the corresponding MFC/PEI with a single-network. The Cr(VI) adsorption performance of MFC/PEI-CDs was systematically investigated under different parameters. Kinetic studies indicated that the adsorption process was well described by the pseudo-second-order model. Isothermal adsorption behaviors accorded well with Langmuir model with the maximum adsorption capacity of 545.1 mg/g, which was superior to most adsorption materials. More importantly, the MFC/PEI-CD was applied to dynamically adsorb Cr(VI) with the treatment volume of 2070 mL/g. Therefore, this work demonstrates that the synergy of cryogelation and double-network is a novel method for preparing macro-porous and robust materials with promising heavy metal removal from wastewater.

A General Procedure for the Construction of 2-Alkyl-Substituted Vinyl Sulfonyl Fluoride

A series of compact and multifunctional 2-alkyl-substituted vinyl sulfonyl fluorides were efficiently prepared from the corresponding alkyl iodides and 2-chloroprop-2-ene-1-sulfonyl fluoride (CESF). This Giese-type radical approach provided new and general access to alkenyl sulfonyl fluorides, including structures that would otherwise be challenging to synthesize with previously established methods. A correspondingly large collection of derivatization reactions was also demonstrated on the alkenyl sulfonyl fluorides.

New Crosslinked Single-Ion Silica-PEO Hybrid Electrolytes.

New single-ion hybrid electrolytes have been synthetized via an original and simple synthetic approach combining Michael addition, epoxidation, and sol-gel polycondensation. We designed an organic PEO network as a matrix for the lithium transport, mechanically reinforced thanks to crosslinking inorganic (SiO1.5) sites, while highly delocalized anions based on lithium vinyl sulfonyl(trifluoromethane sulfonyl)imide (VSTFSILi) were grafted onto the inorganic sites to produce single-ion hybrid electrolytes (HySI). The influence of the electrolyte composition in terms of the inorganic/organic ratio and the grafted VSTFSILi content on the local structural organization, the thermal, mechanical, and ionic transport properties (ionic conductivity, transference number) are studied by a variety of techniques including SAXS, DSC, rheometry, and electrochemical impedance spectroscopy. SAXS measurements at 25 °C and 60 °C reveal that HySI electrolyte films display locally a spatial phase separation with domains composed of PEO rich phase and silica/VSTFSILi clusters. The size of these clusters increases with the silica and VSTFSILi content. A maximum ionic conductivity of 2.1 × 10-5 S·cm-1 at 80 °C has been obtained with HySI having an EO/Li ratio of 20. The Li+ ion transfer number of HySI electrolytes is high, as expected for a single-ion electrolyte, and comprises between 0.80 and 0.92.

Development and post-functionalization of a colorless universal coating using Bis(vinyl sulfonyl)methane

Herein we reported a colorless universal and stable coating through Bis(vinyl sulfonyl)methane (BVS) polymerization that occurs on a broad range of inorganic and organic material surfaces. A set of organic bases were screened, and 1-methylimidazole was selected as the initiator. Michael addition, polymerization and crosslinking were proposed as the major stages for the coating growth. Hydrophobicity, roughness, film thickness, elemental composition, and post-reaction sites of the coating were characterized by complementary surface analysis techniques. Several functionalized coatings were demonstrated after treatments of the post-reaction sites, including nucleic acid detection, protein adsorption resistance, and biocompatible cell adhesion. Due to the covalent bond between coatings and surfaces, the surface was stable even under ultrasound, in strong acid, or after moist-heat sterilization. Rather than the oily darkness of the polydopamine (PDA) coating, our coatings are transparent to white which is much more visually comfortable for patients and medical personnel. Polybis(vinyl sulfonyl)methane (PBVS) coating provides remarkable visual appealingness, universality, mechanic stability, and easiness in preparation and functionalization for multiple end-users.

γ C-H Functionalization of Amines via Triple H-Atom Transfer of a Vinyl Sulfonyl Radical Chaperone.

A selective, remote desaturation has been developed to rapidly access homoallyl amines from their aliphatic precursors. The strategy employs a triple H-atom transfer (HAT) cascade, entailing (i) cobalt-catalyzed metal-HAT (MHAT), (ii) carbon-to-carbon 1,6-HAT, and (iii) Co-H regeneration via MHAT. A new class of sulfonyl radical chaperone (to rapidly access and direct remote, radical reactivity) enables remote desaturation of diverse amines, amino acids, and peptides with excellent site-, chemo-, and regioselectivity. The key, enabling C-to-C HAT step in this cascade was computationally designed to satisfy both thermodynamic (bond strength) and kinetic (polarity) requirements, and it has been probed via regioselectivity, isomerization, and competition experiments. We have also interrupted this radical transfer dehydrogenation to achieve γ-selective C-Cl, C-CN, and C-N bond formations.

(3+2) Cycloadditions of Vinyl Sulfonyl Fluorides with Ethyl Diazoacetate or Azides: Metal-Free Synthesis of Pyrazole and Triazole Scaffolds via SO2 Elimination

AbstractA (3+2) cycloaddition reaction between substituted vinyl sulfonyl fluorides and ethyl diazoacetate or azides for the rapid construction of pyrazole or triazole cores via Michael addition and SO2 gas elimination is developed. Trimethylsilyl azide or organic azide selectively attacks at the β-carbon of vinyl sulfonyl fluoride rather than at the S(VI) center and generates C-substituted or C,N-disubstituted triazole. In contrast, vinyl sulfonyl fluorides react with ethyl diazoacetate to generate pyrazoles in good to high yields.

Regio- and Stereoselective Installation of Bromide onto Vinyl Sulfonyl Fluorides: Construction of a Class of Versatile Sulfur Fluoride Exchange Hubs

A convenient protocol for the exclusively regio- and stereoselective installation of a bromine atom on the 2-arylvinylsulfonyl fluorides using lithium bromide (LiBr) as the bromine source was described, providing (Z)-1-bromo-2-arylethene-1-sulfonyl fluorides (Z-BASF) with versatile reactive handles (bromide, vinyl, and sulfonyl fluoride) in ≤88% yield. Meanwhile, Z-BASF molecules displayed various reactivities in a series of chemical transformations.

Vinyl sulfonyl chemistry-driven unidirectional transport of a macrocycle through a [2]rotaxane

The pH- and chemically-driven unidirectional transport of a macrocycle through a [2]rotaxane based on the vinyl sulfonyl groups is reported.

A Simple Protocol for the Stereoselective Construction of Enaminyl Sulfonyl Fluorides.

A clickable connective hub 1-bromo-2-triazolethane-1-sulfonyl fluoride BTESF (1) was developed and successfully applied for the fluorosulfonylvinylation of a host of primary and secondary cyclic or acyclic amines including amino acids and pharmaceuticals. Further antimicrobial experiments revealed that vinyl sulfonyl fluoride functionalized norfloxacin (3ak), ciprofloxacin (3am), and lomefloxacin (3an) exhibited 4-fold improved antimicrobial activity against Gram-positive bacteria compared to their parent drugs.

Copper-catalyzed mild desulfonylation of vinyl sulfonyl molecules

The first Cu-catalyzed chemical selective desulfonylation of vinyl sulfonyl molecules to olefins was developed using B2pin2–water as the reductant.

2]Rotaxane End‐Capping Synthesis by Click Michael‐Type Addition to the Vinyl Sulfonyl Group

We report the application of the click Michael-type addition reaction to vinyl sulfone or vinyl sulfonate groups in the synthesis of rotaxanes through the threading-and-capping method. This methodology has proven to be efficient and versatile as it allowed the preparation of rotaxanes using template approaches based on different noncovalent interactions (i.e., donor-acceptor π-π interactions or hydrogen bonding) in yields of generally 60-80 % and up to 91 % aided by the mild conditions required (room temperature or 0 °C and a mild base such as Et3 N or 4-(N,N-dimethylamino)pyridine (DMAP)). Furthermore, the use of vinyl sulfonate moieties, which are suitable motifs for coupling-and-decoupling (CAD) chemistry, implies another advantage because it allows the controlled chemical disassembly of the rotaxanes into their components through nucleophilic substitution of the sulfonates resulting from the capping step with a thiol under mild conditions (Cs2 CO3 and room temperature).

“Michael addition” reaction onto vinyl sulfonyl(trifluoromethylsulfonyl)imide: An easy access to sulfonyl(trifluoromethylsulfonyl)imide-based monomers and polymers

Sulfonyl(trifluoromethylsulfonyl) imide anion (STFSI, SO2N(−)SO2CF3) is one of the most important sulfonimide groups for organic and material synthesis. However, the synthesis of STFSI-functionalized monomers and related polymers is still a problematic issue, comprising multi-step and complex synthetic processes. To overcome this drawback, we developed a robust and versatile strategy to prepare original STFSI-based monomers using the “Michael addition” reaction conducted in the presence of vinyl sulfonyl(trifluoromethylsulfonyl)imide and either an amine or a malonate derivative. Furthermore, the synthesized monomers were used to prepare the corresponding STFSI-functionalized polymers using step-growth polymerization with potential applications as electrolytes.

3+2] Cycloaddition of an Azomethyne Ylide and Vinyl Sulfonyl Fluorides ― an Approach to Pyrrolidine‐3‐sulfonyl Fluorides

[3+2] Cycloaddition reactions of vinyl sulfonyl fluorides with an in‐situ generated nonstabilized azomethine ylide is described for the first time. The resulting pyrrolidine‐3‐sulfonyl fluorides were obtained in 50–83 % yield on a scale of up to 25 g. Their utility as reagents for sulfur(VI)–fluoride exchange (SuFEx) and some other transformations was also demonstrated.

Ethenesulfonyl fluoride derivatives as telomerase inhibitors: structure-based design, SAR, and anticancer evaluation in vitro

Based on our previous docking model, in order to carry out more rational drug design, totally 82 vinyl sulfonyl fluorides, including some 2-(hetero)arylethenesulfonyl fluorides and 1,3-dienylsulfonyl fluorides derivatives as potential human telomerase inhibitors were designed and synthesised. The in vitro anticancer activity assay showed that compound 57 (1E,3E)-4-(4-((E)-2-(fluorosulfonyl)vinyl)phenyl)buta-1,3-diene-1-sulfonyl fluoride exhibited high activity against A375 and MDA-MB-231 cell lines with IC50 1.58 and 3.22 µM, but it manifested obvious un-toxic effect against GES-1 and L-02 with IC50 with IC50 values less than 2.00 mM. By the modified TRAP assay, some compounds including 57 exhibited potent inhibitory activities against telomerase with IC50 values of 0.71–0.97 µM.

Proteasome inhibition by new dual warhead containing peptido vinyl sulfonyl fluorides

The success of inhibition of the proteasome by formation of covalent bonds is a major victory over the long held-view that this would lead to binding the wrong targets and undoubtedly lead to toxicity. Great challenges are now found in uncovering ensembles of new moieties capable of forming long lasting ties. We have introduced peptido sulfonyl fluorides for this purpose. Tuning the reactivity of this electrophilic trap may be crucial for modulating the biological action. Here we describe incorporation of a vinyl moiety into a peptido sulfonyl fluoride backbone, which should lead to a combined attack of the proteasome active site threonine on the double bond and the sulfonyl fluoride. Although this led to strong proteasome inhibitors, in vitro studies did not unambiguously demonstrate the formation of the proposed seven-membered ring structure. Possibly, formation of a seven-membered covalent adduct with the proteosomal active site threonine can only be achieved within the context of the enzyme. Nevertheless, this dual warhead concept may provide exclusive possibilities for duration and selectivity of proteasome inhibition.