Sulfinate Salts Research Articles

Benzothiazole Sulfinate: A Sulfinic Acid Transfer Reagent under Oxidation-Free Conditions.

Sulfinic acids are commonly encountered intermediates found in natural product synthesis and medicinal chemistry. However, because of high reactivity, instability, and harsh reaction conditions, they are difficult to synthesize. Herein we have developed an oxidation-free method to produce sulfinic acids and sulfinate salts using 2-sulfinyl benzothiazole (BTS). We have also demonstrated the synthetic usefulness by developing one-pot syntheses of sulfones and sulfonamides.

Late-stage electron-catalyzed perfluoroalkylation of coumarin derivatives—Thermal fluoroalkyl radical production from sodium perfluoroalkyl sulfinate salts

Novel and high-yielding protocols for the late-stage synthesis of 3-perfluoroalkyl-substituted coumarin derivatives employing either perfluoroalkyl iodides RFI or sodium perfluoroalkylsulfinate salts NaSO2RF as perfluoroalkyl RF radical precursors is presented. The electron-catalyzed methodologies make use of two comparative and parallel protocols as an entry to the production of RF radicals: (i) from NaSO2Rf sources and the thermal tert-butylhydroperoxide (TBHP) radical initiation in MeCN: CH2Cl2 as organic solvent mixture, and (ii) from commercial RFI and the photoorganocatalyst anthraquinone-2-sulfonic acid as the room-light initiation process in DMF: CH2Cl2 as mixture of solvents.

Photocatalytic Oxidation of Sulfinates to Vinyl Sulfones with Cyanamide‐Functionalised Carbon Nitride

The cyanamide‐functionalised carbon nitride (NCN‐CNx) can be employed as a photo‐redox catalyst for the light‐induced sulfonylation of alkenes with sulfinate salts, attaining product yields twice those obtained with the non‐functionalised counterpart and comparable to those achieved with the benchmark homogeneous photocatalyst Eosin Y. NCN‐CNx as a heterogeneous photocatalyst is easily isolatable and can be re‐used for this reaction for over three cycles. This photocatalytic reaction can proceed with various sulfinates (aryl‐, alkyl‐ and thiophene‐based) and alkenes with electron‐donating and ‐withdrawing groups, obtaining good to excellent product yields. A reductive quenching route was determined to be the likely mechanism for this photocatalyst.

Iodine/TBHP‐Promoted One‐Pot Deoxygenation and Direct 2‐Sulfonylation of Quinoline N‐Oxides with Sodium Sulfinates: Facile and Regioselective Synthesis of 2‐Sulfonylquinolines

A highly efficient iodine/TBHP‐mediated one‐pot deoxygenative and regioselective 2‐sulfonylation of quinoline N‐oxides with sodium sulfinate salts has been developed. This metal‐, base‐, and phosphorus‐free protocol employs readily accessible and easy‐to‐handle reagents and can be conveniently carried out at room temperature under mild conditions, providing an alternative access to a series of 2‐sulfonylquinolines and other related heteroaryl sulfone products in moderate‐to‐excellent yields within a short reaction time.

Copper-Mediated Nucleophilic Addition/Cascade Cyclization of Aryl Diynes.

Treatment of diyne substrates with sulfinate salts under the action of copper(II) triflate results in a cascade cyclization reaction. The reaction involves nucleophilic addition of the sulfinate and formation of two new C-C bonds with concomitant cleavage of an aryl C-H bond. The reaction proceeds in good yields with a range of diyne precursors and sulfinate salts. Preliminary mechanistic analysis reveals a rare example of an operative ionic mechanism in contrast to other related cyclizations.

Synthesis of Sulfones and Sulfonamides via Sulfinate Anions: Revisiting the Utility of Thiosulfonates.

Simple and high-yielding strategies for the production of a variety of sulfones and sulfonamides, using thiosulfonates synthesized by copper-catalyzed aerobic dimerization, are reported. Although thiosulfonates are an old class of compound, practical methods for their synthesis and utilization have not been rigorously developed. In this study, we revisit the reactions of easily accessible thiosulfonates to form sulfinate anions. Because of the similar reactivity of thiosulfonates and metal sulfinates derived from toxic SO2, thiosulfinates are proposed to be stable, nontoxic alternatives to metal sulfinate salts.

Two-step conversion of carboxylic esters into distally fluorinated ketones via ring cleavage of cyclopropanol intermediates: application of sulfinate salts as fluoroalkylating reagents.

Tertiary cyclopropanols easily available from carboxylic esters have been used in the synthesis of distally fluorinated ketones. Cyclopropane ring cleavage reactions in methanol with aqueous tert-butyl hydroperoxide in the presence of a copper(ii) acetate catalyst and sodium triflinate (Langlois reagent) afford β-trifluoromethyl ketones in 16-74% isolated yields. Sodium triflinate serves as a precursor of reactive trifluoromethyl copper species, enabling ring-opening trifluoromethylation, as evidenced by mechanistic studies. We also demonstrate here that other sulfinate salts, such as sodium 1,1-difluoroethanesulfinate, sodium 2-(4-bromophenyl)-1,1-difluoroethanesulfinate and sodium 1-(trifluoromethyl)cyclopropanesulfinate, can be used as fluoroalkylation reagents, resulting in the corresponding fluorinated ketones.

Synthesis of γ-keto sulfones by copper-catalyzed oxidative sulfonylation of tertiary cyclopropanols.

Tertiary cyclopropanols undergo ring-opening oxidative sulfonylation to afford γ-keto sulfones when reacting with sulfinate salts in the presence of a copper(ii) acetate catalyst and an oxidant (tert-butyl hydroperoxide or atmospheric oxygen). Various fluoroalkyl, aryl and alkyl sulfinate salts are successfully employed as sulfonylation reagents, affording the corresponding sulfones in up to 94% yields. The experimental protocol is mild and tolerates a number of functionalities in the cyclopropanol substrate. The reaction proceeds via a one-pot oxidation-Michael addition mechanism and can serve as a useful addition to the existing methods for the preparation of γ-keto sulfones based on the sulfa-Michael reaction.

Efficient synthesis of aliphatic sulfones by Mg mediated coupling reactions of sulfonyl chlorides and aliphatic halides.

Sulfonyl chlorides were reduced to anhydrous sulfinate salts with magnesium under sonication. These sulfinates were alkylated to sulfones with alkyl chlorides in the presence of catalytic sodium iodide under sonication. A variety of aliphatic sulfones was efficiently prepared by this one-pot two-step procedure.

Unique Reactivity of α‐Substituted Electron‐Deficient Allenes using Sulfinate Salts as Lewis Base Organocatalysts

AbstractThe efficient sulfinate‐catalyzed intermolecular addition reaction of α‐substituted allenyl sulfones and allenoates with Michael acceptors is highlighted. The sequence proceeds under mild conditions to provide a scalable and efficient access to versatile functionalized alkynes, displaying a quaternary stereocentre at the propargylic position. This work enriches the diversity of Lewis base organocatalysts in the field of allene chemistry, in addition to the well‐established phosphine and amine catalysts.magnified image

Copper‐Mediated Oxidative Radical Addition/Cyclization Cascade: Synthesis of Trifluoromethylated and Sulfonated Quinoline‐2,4(1H,3H)‐diones

AbstractA copper‐mediated oxidative radical addition/cyclization cascade of o‐cyanoarylacrylamides with sodium trifluoromethanesulfonate (Langlois’ reagent) has been achieved. The reaction proceeds through radical addition, cyclization, and imine hydrolysis, in which the cyclization was accomplished by an intramolecular addition of the carbon radical to the nitrile. This transformation exhibits a wide substrate scope and good functional group tolerance, thus providing a highly efficient and practical access to a variety of trifluoromethylated quinoline‐2,4(1H,3H)‐diones. Furthermore, using other sulfinic acid sodium salts as sulfonylating agents, sulfonated quinolinediones were also obtained through a similar radical cascade.magnified image

ChemInform Abstract: Eosin Y (EY) Photoredox‐Catalyzed Sulfonylation of Alkenes: Scope and Mechanism.

AbstractAlkyl‐ and aryl vinyl sulfones are obtained by eosin Y (EY)‐mediated visible‐light photooxidation of sulfinate salts and reaction of the resulting S‐centered radicals with alkenes.

Tagging the Untaggable: A Difluoroalkyl-Sulfinate Ketone-Based Reagent for Direct C-H Functionalization of Bioactive Heteroarenes.

We have developed a new difluoroalkyl ketal sulfinate salt reagent suitable for direct derivatization of heteroarene C-H bonds. The reagent is capable of introducing a ketone functional group on heteroarene bioactive compounds via a one-pot reaction. Remarkably, in three examples the ketone analog and its parent drug had almost identical cytotoxicity. In a representative example, the ketone analog was bioconjugated with a delivery vehicle via an acid-labile semicarbazone linkage and with a photolabile protecting group to produce the corresponding prodrug. Controlled release of the drug-ketone analog was demonstrated in vitro for both systems. This study provides a general approach to obtain taggable ketone analogs directly from bioactive heteroarene compounds with limited options for conjugation. We anticipate that this sodium ketal-sulfinate reagent will be useful for derivatization of other heteroarene-based drugs to obtain ketone-taggable analogs with retained efficacy.

Efficient Synthesis of Vinyl Sulfones by Manganese-Catalyzed Decarboxylative Coupling of Cinnamic Acids with Aromatic Sulfinic Acid Sodium Salts

An efficient synthesis of vinyl sulfones is described. Reactions of cinnamic acids with aromatic sulfinic acid sodium salts in the presence of a catalytic amount of manganese(II) acetate tetrahydrate (5 mol%) in dimethyl sulfoxide (DMSO) afforded the desired vinyl sulfones in good to excellent yields. Notably, the reaction does not need any base or iodide as additive. The use of DMSO as the solvent and running the reaction under air are critical in achieving good yields.

ChemInform Abstract: Olefin Synthesis by the Pd‐Catalyzed Cross Coupling on Sulfonylhydrazones with Aromatic Sulfinates.

AbstractElectron‐rich sulfinates react under oxidative conditions with electron‐deficient arylsulfonylhydrazones to afford the corresponding olefins.

Photocatalytic Anion Oxidation and Applications in Organic Synthesis.

Ions and radicals of the same kind differ by one electron only. The oxidation of many stable inorganic anions yields their corresponding highly reactive radicals, and visible light excitable photocatalysts can provide the required oxidation potential for this transformation. Air oxygen serves as the terminal oxidant, or cheap sacrificial oxidants are used, providing a very practical approach for generating reactive inorganic radicals for organic synthesis. We discuss in this perspective several recently reported examples: Nitrate radicals are obtained by one-electron photooxidation of nitrate anions and are very reactive toward organic molecules. The photooxidation of sulfinate salts yields the much more stable sulfone radicals, which smoothly add to double bonds. A two-electron oxidation of chloride anions to electrophilic chlorine species reacting with arenes in aromatic substitutions extends the method beyond radical reactions. The chloride anion oxidation proceeds via photocatalytically generated peracidic acid as the oxidation reagent. Although the number of reported examples of photocatalytically generated inorganic radical intermediates for organic synthesis is still small, future extension of the concept to other inorganic ions as radical precursors is a clear perspective.

Eosin Y (EY) Photoredox-Catalyzed Sulfonylation of Alkenes: Scope and Mechanism.

Alkyl- and aryl vinyl sulfones were obtained by eosin Y (EY)-mediated visible-light photooxidation of sulfinate salts and the reaction of the resulting S-centered radicals with alkenes. Optimized reaction conditions, the sulfinate and alkene scope, and X-ray structural analyses of several reaction products are provided. A detailed spectroscopic study explains the reaction mechanism, which proceeds through the EY radical cation as key intermediate oxidizing the sulfinate salts.

Olefin synthesis by the Pd-catalyzed cross coupling on sulfonylhydrazones with aromatic sulfinates

This Letter describes the synthesis of olefins by coupling of electron deficient sulfonylhydrazones with aryl sulfinate salts in the presence of a palladium(II) catalyst under aerobic conditions. This methodology obviates the need for preparation of an organometallic and separate activation of the ketone starting material via a vinyl halide or triflate. The oxidant, reagent stoichiometry, and the electronics of the sulfinate coupling partner are reported.

Desulfination as an Emerging Strat­egy in Palladium‐Catalyzed C–C Coupling Reactions

AbstractAs carbon–carbon bonds are an essential bond type in Nature, reactions that form C–C bonds are of great interest in organic chemistry. Among the most popular C–C bond formation methods with aromatic systems are palladium‐catalyzed coupling reactions, such as the Heck, Suzuki, Negishi and Stille reactions. Even though these methods are efficient, they produce stoichiometric amounts of high molecular weight byproducts, placing them in conflict with the increasingly important ideas of sustainable reactions and green chemistry. In contrast, palladium‐catalyzed desulfinative coupling reactions produce minimal waste; in general, only hydrogen halides or alkali halides are formed as byproducts in addition to SO2 gas, which can potentially be recycled. This microreview provides a brief historic overview on palladium‐catalyzed coupling reactions with organosulfur compounds, with the main focus on the use of sulfinate salts as nucleophilic or electrophilic reaction partners. Various methods to access the sulfinate salts, and the coupling reactions of sulfonyl precursors that proceed through sulfinic acid/salt intermediates generated in situ are also discussed.

ChemInform Abstract: Efficient Palladium‐Catalyzed Synthesis of Sulfonyl‐Substituted Vinyl Arenes: Hydrazones Provide the Cross‐Coupling Partner and Nucleophile Components.

A practical and efficient approach for the synthesis of various sulfonyl-substituted vinyl arenes is reported. In the process, hydrazones provide coupling partners for the Pd-catalyzed cross-coupling with aryl halides and sulfinate salts as nucleophiles, which realizes minimal waste and excellent atom economy.