Sulfonate Research Articles

α-Diazo-λ3-iodanes and α-diazo sulfonium salts: the umpolung of diazo compounds.

This minireview aims to cover the developments of the last few years in the design of reagents able to accomplish the umpolung of the azomethine carbon in diazo compounds namely, α-diazo-λ3-iodanes and α-diazo sulfonium salts. Specifically, the routes available for their preparation and a classification of their unique reactivity patterns (either acting as equivalents of carbene-radical or carbene-carbocation synthons) are discussed. We also present a detailed overview of the synthetic utility of such species and, when possible, a critical comparation their reactivity and properties.

Enantioselective construction of dihydropyranone-fused indoles by [3 + 3] annulation of in situ-derived indolin-3-ones and unsaturated carboxylic esters

This work discloses an N-heterocyclic carbene (NHC) and base-mediated [3 + 3] annulation reaction of unsaturated carboxylic esters and sulfonium salts for rapid and direct access to enantioselective dihydropyrano[3,2-b]indoles.

3 + 2] Cycloaddition of azides with arynes formedviaC–H deprotonation of aryl sulfonium salts

Herein, we developed a new methodology of using aryl sulfonium salts as the aryne precursor for [3 + 2] cycloaddition reactions with azides.

Anti-Markovnikov Ring-Opening of Sulfonium Salts with Alkynes Catalyzed by Visible Light/Copper

Anti-Markovnikov Ring-Opening of Sulfonium Salts with Alkynes Catalyzed by Visible Light/Copper

Photoredox-catalyzed coupling of aryl sulfonium salts with CO2 and amines to access O-aryl carbamates.

An efficient photoredox-catalyzed three-component coupling reaction of aryl sulfonium salts, carbon dioxide and amines has been developed for the first time. This reaction provides a new strategy for the synthesis of a range of valuable O-aryl carbamates from readily available arenes via a site-selective thianthrenation/carbamoyloxylation two-step process. Mild conditions, broad substrate scope and good functional group tolerance are the features of the transformation. The synthetic utility of the method was demonstrated by the late-stage modification of bioactive molecules and pharmaceuticals.

Copper-catalyzed ring-opening sulfonylation of cyclopropanols via the insertion of sulfur dioxide toward the synthesis of γ-keto aryl sulfones

A copper-catalyzed three-component sulfonylation reaction is presented. This protocol provides easy and straightforward access to structurally diverse γ-keto aryl sulfones with good yields, mild reaction conditions, low catalyst loading, and good functional group tolerance.

Nickel catalyzed three-component sulfonylation of non-activated alkyl chlorides.

We describe a nickel-catalyzed three-component sulfonylation of readily available non-activated alkyl chlorides. A wide range of alkyl aryl sulfones can be synthesized from alkyl chlorides, aryl boronic acids, and potassium metabisulfite, a cheap, efficient, and commercially available SO2 source under simple and easy-to-handle reaction conditions. High selectivity can be achieved with a slight excess of phenylboronic acid and a sulfur dioxide source.

Aryl sulfonate anion stabilized aromatic triangular cation [Pd3]+: syntheses, structures and properties.

A series of sulfonate anions paired aromatic triangular palladium clusters 3-7, abbreviated as [Pd3]+[ArSO3]-, were synthesized using a simple "one pot" method, and gave excellent isolated yields (90-95%). Their structures and properties have been fully characterized and further investigated by fluorescence, single crystal X-ray Diffraction (XRD) and X-ray Photoelectron Spectroscopy (XPS). In varying organic solvents, they presented apparently stronger absorption and emission in MeOH, driven by the combined interactions of hydrogen bonds and polarity. The crystallographic data demonstrated that the methyl orange ion stabilized complex 7 possessed a D3h symmetric metallic core which was still coplanar and almost equilateral, jointly influenced by the giant hindrance and milder donating effect from the sulfonate. The binding energies for Pdn+ 3d5/2 and Pdn+ 3d3/2 measured by XPS presented at 336.55 and 342.00 eV, respectively. These data were much lower than that of a usual Pd2+ 3d and significantly higher than that of a Pd0 species, further proving the unified palladium valence state (+4/3) in the tri-palladium core and its aromaticity featured by the cyclic electron delocalization.

S-Adenosylmethionine: more than just a methyl donor.

Covering: from 2000 up to the very early part of 2023S-Adenosyl-L-methionine (SAM) is a naturally occurring trialkyl sulfonium molecule that is typically associated with biological methyltransfer reactions. However, SAM is also known to donate methylene, aminocarboxypropyl, adenosyl and amino moieties during natural product biosynthetic reactions. The reaction scope is further expanded as SAM itself can be modified prior to the group transfer such that a SAM-derived carboxymethyl or aminopropyl moiety can also be transferred. Moreover, the sulfonium cation in SAM has itself been found to be critical for several other enzymatic transformations. Thus, while many SAM-dependent enzymes are characterized by a methyltransferase fold, not all of them are necessarily methyltransferases. Furthermore, other SAM-dependent enzymes do not possess such a structural feature suggesting diversification along different evolutionary lineages. Despite the biological versatility of SAM, it nevertheless parallels the chemistry of sulfonium compounds used in organic synthesis. The question thus becomes how enzymes catalyze distinct transformations via subtle differences in their active sites. This review summarizes recent advances in the discovery of novel SAM utilizing enzymes that rely on Lewis acid/base chemistry as opposed to radical mechanisms of catalysis. The examples are categorized based on the presence of a methyltransferase fold and the role played by SAM within the context of known sulfonium chemistry.

Keggin Cluster Modulated Photocatalytic Activity of Aryl Sulfonium Polyoxometalate Hybrids toward Dichromate Reduction

Dichromate (Cr2O72-) ion having chromium in its +6 oxidation state is a carcinogen and a potential threat to humans and aquatic life. The photocatalytic reduction of toxic Cr(VI) species into less toxic Cr(III) is an important target in heterogeneous catalysis. In this work, the catalytic activities of a series of Keggin cluster-based aryl sulfonium polyoxometalate hybrids, (FPDS)3[PMo12O40] (1), (FPDS)3[PW12O40] (2), (FPDS)4[SiMo12O40] (3), and (FPDS)4[SiW12O40] (4), toward the photocatalytic reduction of Cr(VI) have been analyzed and compared. Here, we used the aryl sulfonium counterions to modulate the POM cluster's solubility in water and stabilize the photogenerated e--h+ pair on the cluster. All of the hybrids 1-4 catalyzed the reduction of Cr(VI) to Cr(III) under ultraviolet (UV) irradiation, and their photocatalytic efficiencies followed the order hybrid 1 > hybrid 3 > hybrid 2 > hybrid 4, with the rate-constant values of 0.048, 0.0056, 0.0035, and 0.0028 min-1, respectively. Hybrid 1 with [PMo12O40]3- Keggin cluster exhibited the best photocatalytic activity in the series yielding a 99% reduction in 120 min. The reasons behind the best photocatalytic activity of hybrid 1 are identified as its low band gap, less charge recombination, and fast photoresponse. The electron-trapping analyses performed using AgNO3 revealed electrons as the main reactive species responsible for the photocatalytic reduction of Cr(VI). A plausible photocatalytic mechanism has also been proposed based on electron-trapping experiments. The present study shows that aryl sulfonium Keggin hybrids can function as efficient photocatalysts for Cr(VI) reduction, and their catalytic efficiency varies with the nature of the Keggin cluster.

Facile Entry to Pharmaceutically Important 3-Difluoromethyl-quinoxalin-2-ones Enabled by Visible-Light-Driven Difluoromethylation of Quinoxalin-2-ones.

CF2H moiety has a significant potential utility in drug design and discovery, and the incorporation of CF2H into biologically active molecules represents an important and efficient strategy for seeking lead compounds and drug candidates. On the other hand, quinoxalin-2-one is of great interest to pharmaceutical chemists as a common skeleton frequently occurring in plenty of natural products and bioactive compounds. Herein, we reported a practical and efficient protocol for the synthesis of 3-CF2H-quinoxalin-2-ones. Thus, in the presence of 3 mol% of photocatalyst and S-(difluoromethyl)sulfonium salt as difluoromethyl radical sources, a wide range of quinoxalin-2-ones readily underwent a visible-light redox-catalyzed difluoromethylation reaction, to deliver structurally diverse 3-difluoromethyl-quinoxalin-2-ones. We believe that this would facilitate increasing chances and possibilities for seeking potential lead compounds and drug candidates and further boost the development of fluorine-containing pharmaceuticals.

Mixed Organic Counterion Strategy Modulates the Self-Assembly of Polyoxometalate Hybrids into Toroids and Affects Their Photochromic and Photocatalytic Properties.

A series of five mixed-counterion polyoxometalate (POM) hybrids 1-5 have been developed starting from the [SiW12O40]4- cluster and two different aryl sulfonium counterions (ASCIs), (4-hydroxyphenyl)dimethylsulfonium (HPDS) and (4-formylphenyl)dimethylsulfonium (FPDS), bearing different functional groups -OH and -CHO, respectively. The HPDS/FPDS counterion ratio in hybrids 1-5 varied as 4:0 (1), 3:1 (2), 2:2 (3), 1:3 (4), and 0:4 (5), and it resulted in a morphological transition of the self-assembly of these hybrids. Hybrid 1 exhibited spherical self-assembly, while hybrid 5 exhibited large toroidal self-assembly predominantly. The hybrids 2-4 gave a mixture of spherical, dimpled spherical, and toroidal self-assemblies in varying amounts, indicating a gradual transition of self-assembly from spherical to toroidal as the percentage of FPDS increases in the system. A plausible explanation for the differences in the self-assembly properties of these hybrids has been proposed based on the differences in the H-bonding interactions of the two counterions with the dispersion medium. The HPDS and FPDS counterions exhibited different HOMO-LUMO gaps, and their varying percentages in hybrids 1-5 led to differences in optical band gaps and photochromic activities. Hybrid 2 showed the lowest band gap value and the best photochromic activity (t1/2 = 0.72 min) in the series. The influence of the mixed-counterion strategy in catalysis has been demonstrated by evaluating the photocatalytic activity of these hybrids toward rhodamine B dye degradation. The hybrid 4, exhibiting stable toroidal self-assembly, showed the best catalytic activity in the series, probably due to a combination of reasons such as the enhanced surface area due to toroid formation and also the presence of H-bonding -OH functionality on the counterion. Therefore, the present study suggests a new method for altering the self-assembly and the materials and catalytic properties of POM hybrids through a mixed-counterion strategy.

Visible‐Light‐Induced Radical Type Ring‐Opening of Sulfonium Salts with Heteroarenes by Copper Photocatalyst

AbstractIn this manuscript, we report a radical type ring‐opening of sulfonium salts with heteroarenes under visible light conditions. This developed method does not require noble metal photocatalysts, or stoichiometric amount of external oxidants, and has a application prospect in the synthesis of organosulfur compounds and bioactive molecules. This radical type ring‐opening photocatalytic system could inspire further applications of sulfonium salts in C(sp3)−C(sp2) bond forming reactions.magnified image

The Use of Polydialkylsiloxanes/Triflic Acid as Derivatization Agents in the Analysis of Sulfur-Containing Aromatics by “Soft”-Ionization Mass Spectrometry

Polycyclic aromatic sulfur-containing compounds are widely distributed in oil, especially in its low-volatile and heavy fractions (resins, asphaltenes), and this dictates the need for their determination when reliable methods for sulfur removing, cleaning and processing oil are developed. In these cases, "soft" ionization mass spectrometry methods, based on electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI), are particularly effective. However, aromatic sulfur-containing compounds have low polarity and cannot be readily ionized by these methods. To overcome the problem, their preliminary conversion into sulfonium salts by the action of alkyl iodides and a silver-containing agent is widely used. In the process of developing more economical derivatization methods, we found a rather unexpected possibility of implementing S-alkylation of organic sulfides with commercial polydialkylsiloxanes (alkyl = CH3 or C2H5) in the presence of triflic acid (CF3SO3H) as a superacid co-alkylating agent. For homologous dibenzothiophenes as a typical model representative of petroleum sulfur-containing aromatic compounds, ESI and MALDI mass spectra exhibited the signals of corresponding S-alkylsulfonium salts with a high signal-to-noise ratio. A rational mechanism for the described chemical transformation is proposed, including the indispensable activation by triflic acid and the cleavage of the Si-C bond. Specific collision-induced dissociation of corresponding S-alkylated sulfonium cations is considered. The applicability of the derivatization approach to the analysis of petroleum products by high-resolution mass spectrometry is demonstrated.

Visible Light-Induced Coupling Cyclization Reaction of α-Diazosulfonium Triflates with α-Oxocarboxylic Acids or Alkynes.

A photocatalyst-free radical cleavage of α-diazo sulfonium salts has been developed for the first time. The reaction provides an efficient method for the generation of diazomethyl radicals from α-diazosulfonium triflates under photochemical conditions. Utilizing the in situ generated diazomethyl radicals as key intermediate, the coupling cyclization reaction of α-diazosulfonium triflates with α-oxocarboxylic acids or alkynes has been achieved. The method affords a diverse set of important 2,5-disubstituted 1,3,4-oxadiazoles and 3,5-disubstituted-1H-pyrazoles with excellent regioselectivity in a single step. A reaction mechanism involving a radical pathway was further supported by control experiments and DFT calculations.

A general arene C-H functionalization strategy via electron donor-acceptor complex photoactivation.

The photoactivation of electron donor-acceptor complexes has emerged as a sustainable, selective and versatile strategy for the generation of radical species. However, when it comes to aryl radical formation, this strategy remains hamstrung by the electronic properties of the aromatic radical precursors, and electron-deficient aryl halide acceptors are required. This has prevented the implementation of a general synthetic platform for aryl radical formation. Our study introduces triarylsulfonium salts as acceptors in photoactive electron donor-acceptor complexes, used in combination with catalytic amounts of newly designed amine donors. The sulfonium salt label renders inconsequential the electronic features of the aryl radical precursor and, more importantly, it is installed regioselectively in native aromatic compounds by C-H sulfenylation. Using this general, site-selective aromatic C-H functionalization approach, we developed metal-free protocols for the alkylation and cyanation of arenes, and showcased their application in both the synthesis and the late-stage modification of pharmaceuticals and agrochemicals.

Gem-Difluoroallylation of Aryl Sulfonium Salts.

The unprecedented photochemical late-stage defluorinative gem-difluoroallylation of aryl sulfonium salts, which are formed site-selectively by direct C(sp2)─H functionalization, is herein disclosed. This method is distinguished by its mild reaction conditions, wide scope, and excellent site-selectivity. As showcase examples, a Flurbiprofen and Pyriproxyfen derivatives could be late stage C(sp2)─H gem-difluoroallylated with high yields. Experimental and computational investigations were conducted.

Synergistic Pd/Cu catalysis enabled cross-coupling of glycosyl stannanes with sulfonium salts to access C-aryl/alkenyl glycals

A highly efficient coupling of glycosyl stannanes and sulfonium salts enabled by synergistic Pd/Cu catalysis is disclosed, facilitating the construction of C-aryl/alkenyl glycals under mild conditions in high yields. The protocol tolerates a wide scope of functional groups including ketone, cyano, ester, amide, nitro, halide. The one-pot formal CH glycosylation starting from arene is demonstrated with a reaction sequence of dibenzothiophenylation/Stille coupling. Besides, a gram-scale reaction is performed successfully, showing the high applicability of this protocol.

Nucleophilic Substitution at Tricoordinate Sulfur-Alkaline Hydrolysis of Optically Active Dialkoxysulfonium Salts: Stereochemistry, Mechanism and Reaction Energetics.

Optically active dialkoxyisopropylsulfonium salts were obtained by methylation (ethylation) of optically active alkyl isopropanesulfinates using methyl (ethyl) trifluoromethanesulfonate. Alkaline hydrolysis of a series of methoxy(alkoxy)sulfonium salts afforded the two sulfinate products methyl isopropanesulfinate and alkyl isopropanesulfinate, both formed with a slightly prevailing inversion of configuration at the sulfur atom. DFT calculations revealed that this substitution reaction proceeded stepwise according to an addition-elimination (A-E) mechanism involving the formation of high tetracoordinate SIV sulfurane intermediates. In addition, the DFT calculations showed that recombination of the hydroxy anion with the methoxy(alkoxy)sulfonium cation-leading to the parallel formation of the two most stable primary sulfuranes, with the hydroxy and alkoxy groups in apical positions and their direct decomposition-is the most energetically favorable pathway.

Anti-Markovnikov ring-opening of sulfonium salts with alkynes by visible light/copper catalysis

Anti-Markovnikov ring-opening of sulfonium salts with alkynes by visible light/copper catalysis