Dechalcogenative allylic selenosulfide and disulfide rearrangements: complementary methods for the formation of allylic sulfides in the absence of electrophiles. Scope, limitations, and application to the functionalization of unprotected peptides in aqueous media

Primary allylic selenosulfates (seleno Bunte salts) and selenocyanates transfer the allylic selenide moiety to thiols giving primary allylic selenosulfides, which undergo rearrangement in the presence of PPh3 with the loss of selenium to give allylically rearranged allyl alkyl sulfides. This rearrangement may be conducted with prenyl-type selenosulfides to give isoprenyl alkyl sulfides. Alkyl secondary and tertiary allylic disulfides, formed by sulfide transfer from allylic heteroaryl disulfides to thiols, undergo desulfurative allylic rearrangement on treatment with PPh3 in methanolic acetonitrile at room temperature. With nerolidyl alkyl disulfides this rearrangement provides an electrophile-free method for the introduction of the farnesyl chain onto thiols. Both rearrangements are compatible with the full range of functionality found in the proteinogenic amino acids, and it is demonstrated that the desulfurative rearrangement functions in aqueous media, enabling the derivatization of unprotected peptides. It is also demonstrated that the allylic disulfide rearrangement can be induced in the absence of phosphine at room temperature by treatment with piperidine, or simply by refluxing in methanol. Under these latter conditions the reaction is also applicable to allyl aryl disulfides, providing allylically rearranged allyl aryl sulfides in good yields.     

二碘化钐促进的二硫代氨基甲酸酯和硫代氨基甲酸酯的还原断裂反应

室温下SmI2-THF-HMPA-t-BuOH体系可顺利地将二硫代氨基甲酸酯还原断裂得到二硫醚和硫代甲酰胺; 同样条件下, 硫代氨基甲酸酯还原断裂得到二硫醚篅34The reductive cleavage of dithiocarbamic esters are promoted by the SmI2-HMPA-THF-t-BuOH System successfully to give disulfides and thiocarboxamides at room temperature in good yields; The reduction of thiocarbamic esters are also promoted by the same system to give disulfides and carboxamides.     

Iodine-catalyzed disulfidation of alkenes

The disulfidation reactions of alkenes with disulfides were thoroughly investigated in this paper. Using H₂O or DCE as the solvent, most reactions occurred smoothly to give the corresponding disulfidated products in good to high yields at room temperature within 12 h.     

Stereoselective Synthesis of (Z)-1,2-Diarylthio-1-alkene via the Reaction of Diaryl Disulfides with Terminal Alkynes Catalyzed by Cesium Hydroxide

In the presence of a catalytic amount of cesium hydroxide under a nitrogen atmosphere, terminal alkynes reacted with diaryl disulfides at room temperature in dimethylformamide to give almost exclusively (Z)-1,2-diarylthio-1-alkene in good yields, but under an air atmosphere, the reaction gave a mixture of alkynyl sulfide and (Z)-1,2-diarylthio-1-alkene.     

Substituent effect on the efficiency of desulfurizative rearrangement of allylic disulfides

Crich ligation is a new method for the functionalization of peptides and proteins under mild conditions. To more fully understand the mechanism of the ligation and to explore the effect of substitution on its efficiency, a systematic theoretical study is carried out for the first time. It is found that the MP2 method wrongly predicts the substituent effect whereas the ONIOM(CCSD(T):B3LYP) method overestimates the free energy barriers by ca. 4 kcal/mol. Only the ONIOM(G3B3:B3LYP) method is found to be reliable as well as feasible for studying the ligation. The rate-limiting step of the ligation is found to be the [2,3]-sigmatropic rearrangement of the alkyl allyl disulfide, followed by an S N2 phosphine-mediated desulfurization. The S-S bond is significantly polarized during the rearrangement and, therefore, the reaction proceeds more rapidly in polar solvents. R S and R 3 substitutions elevate the free energy barrier of the ligation, whereas the R 2 substitution does not exert a useful effect. Only the substitution at R 1 can effectively reduce the free energy barrier of the reaction to less than 20 kcal/mol (a value required to allow the reaction to complete in minutes at 25 degrees C). Therefore, secondary and tertiary allyl alkyl disulfides can undergo the ligation at the room temperature. Marcus theory analysis indicates that the major factor for the retardation of the reaction by substituents at R S and R 3 and for the acceleration by substituents at R 1 is the thermodynamic equilibrium between the disulfide and thiosulfoxide. To shift the equilibrium to favor the ligation, placement of substituents at R 1 is obligatory for alkyl allyl disulfides. Nonetheless, alkyl buta-2,3-dienyl disulfides may also undergo the ligation at room temperature without the help of the R 1 substituent.     

一氟甲基二硫化物的高效合成

以PhSO2SCH2F为一氟甲硫基化试剂,室温下实现了硫酚/硫醇的一氟甲硫基化反应,高收率地合成了一系列一氟甲基二硫化物.该方法具有反应时间短、条件温和、操作简单以及无需外加添加剂等特点,为高效制备一氟甲基二硫化物提供了一条简便的途径.     

Rhodium-catalyzed disulfide exchange reaction

A system of RhH(PPh3)4, trifluoromethanesulfonic acid, and (p-tol)3P catalyzes the disulfide exchange reaction. Treatment of two symmetrical dialkyl disulfides with the catalyst provides an equilibrium mixture of three disulfides within 15 min in refluxing acetone. The catalyst is active after reaching the equilibrium, and addition of a disulfide to the mixture changes the ratio of the products. The use of 4 mol equiv excess of one of the disulfides provides the unsymmetrical disulfide in a yield exceeding 80%. Disulfide-containing peptides also undergo an exchange reaction. The reactions of diaryl disulfides and dialkyl disulfides are even faster, and reach equilibrium within 5 min at room temperature in the presence of the rhodium complex and 1,2-bis(diphenylphosphino)ethane (dppe). This exchange reaction is considerably affected by the substituents on the disulfides. Treatment of diphenyl disulfide, di(p-tolyl) disulfide, and bis(sec-butyl) disulfide yields phenyl p-tolyl disulfide at room temperature with unchanged bis(sec-butyl) disulfide; random disproportionation occurs at reflux. The rhodium catalysis can be used for the exchange reaction of disulfides and diselenides giving selenosulfides as well as disulfides and ditellurides giving tellurinosulfides.     

Preparation of Disulfides by Reduction of Sodium Alkyl Thiosulfates with Metallic Samarium and Catalytic Amount of Iodine

Sm/I₂ reduces sodium alkyl thiosulfates to the corresponding disulfides in good to excellent yields in THF at room temperature.     

Reaction of thiolsulfinates with trihaloacetic anhydrides—I : Evidence for the formation of sulfenyl and sulfinyl carboxylates

Thiolsulfinates react with trifluoro- or trichloroacetic anhydride to give equimolar mixtures of the corresponding disulfides and sulfinyl trifluoro- or trichloroacetates which are in equilibria with sulfenyl carboxylates. Although the equilibrium lies far toward sulfinyl carboxylates at room temperature, addition of olefins to the mixed solution of sulfinyl carboxylate and a corresponding disulfide affords the adducts which are formed in the reaction between the corresponding sulfenyl carboxylates and the olefins. Meanwhile, treatment of carboxylic acid silver salts with sulfinyl chlorides also gives sulfinyl carboxylates, however, sulfinyl carboxylates have not been successfully isolated yet.     

Reduction of disulfides in the milligram range with hypophosphorous acid and organic phosphites

A number of organic disulfides in the milligram range were reduced to the corresponding thiol by reaction with hypophosphorous acid at elevated temperatures in aqueous solvents. Reduction is extensive after several hours. Aromatic disulfides were reduced by triethyl phosphite and triphenyl phosphite at room temperature. Products were deterimned by polarographic and amperometric titration techniques.     

Clean and fast oxidative transformation of thiols to disulfides under solvent-free conditions

We present here a fast, solvent-free synthesis of symmetrical disulfides using solid supported catalyst (Al₂O₃/KF). The reaction was performed at room temperature, by gentle heating or under MW irradiation. This efficient and improved method is general for liquid thiols, affording the disulfides in good to excellent yields. The catalytic system can be re-used two times without previous treatment and with comparable activity.     

Visible-light-mediated facile synthesis of disulfides using reusable TiO2/MoS2 nanocomposite photocatalyst

A nontoxic and inexpensive TiO₂/MoS₂ nanocomposite was prepared and employed as an efficient photocatalyst for the synthesis of symmetrical disulfides under visible light irradiation at room temperature. Both aryl and alkyl thiols survived the reaction conditions, affording the corresponding disulfides in good to excellent yields. The photocatalyst could be easily recovered by simple centrifugation and filtration and reused several times without significant loss in its activity.     

Solvent- and metal-free selective oxidation of thiols to disulfides using I2/DMSO catalytic system

We describe herein a simple, fast and inexpensive protocol for the oxidative coupling of thiols employing a stoichiometric amount of DMSO and iodine as the catalyst. Various aromatic disulfides were obtained in good to excellent yields in short reaction times at room temperature, while aliphatic disulfides were achieved in good yields when the reactions were conducted under microwave irradiation.     

Benzyltriethylammon Tetrathiomolybdate: An Improved Sulfur Transfer Reagent for the Synthesis of Disulfides

Benzyltriethylammonium tetrathiomolybdate has been found to be a superior reagent for the conversion of alkyl halides to the corresponding disulfides in chloroform at room temperature.     

Photoinduced intramolecular cyclization of o-ethenylaryl isocyanides with organic disulfides mediated by diphenyl ditelluride

Photoinduced reaction of o-ethenylaryl isocyanides with organic disulfides in the presence of diphenyl ditellurides affords the corresponding bisthiolated indole derivatives via a radical cyclization process. The cyclization can proceed at room temperature upon visible-light irradiation and exhibits good tolerance to functional groups. Several organic disulfides also can be employed for this cyclization, and the corresponding bisthiolated indole derivatives are obtained selectively. In addition, the photoinduced reaction of o-ethenylaryl isocyanides with bis(2-aminophenyl) disulfide affords tetracyclic compounds in one portion.     

An Efficient and Selective Oxidation of Sulfides and Thiols with Silica-Supported 1,1,3,3-Tetramethylguanidine/Br2 Complex

Silica-supported 1,1,3,3-tetramethylguanidine/Br₂ complex is an efficient reagent for the selective oxidation of aliphatic and aromatic sulfides to the corresponding sulfoxides and the oxidative coupling of thiols to disulfides in aqueous solution at room temperature in a short reaction time.     

Rapid and efficient synthesis of symmetrical alkyl disulfides under phase transfer conditions

A one-pot, rapid and general method for the synthesis of symmetrical disulfides based on reaction of sulfur with sodium sulfide in the presence of didecyldimethylammonium bromide (DDAB) as a phase transfer catalyst is reported. Reaction with a variety of alkyl halides, at room temperature, afforded the disulfides in good to excellent isolated yields in a short time.     

Oxidation of disulfides with electrophilic halogenating reagents: concise methods for preparation of thiosulfonates and sulfonyl halides

The reaction of aromatic or benzylic disulfides with 2.5 equiv of Selectfluor™ in acetonitrile/water (10:1) at room temperature efficiently produced the corresponding thiosulfonates. Conversely, the reaction of disulfides with 6.5 equiv of Selectfluor™ or thiosulfonates with 4.5 equiv of Selectfluor™ in refluxing acetonitrile/water (10:1) provided sulfonyl fluorides in high yields. Accufluor™ and FP-T300™ are also effective in preparing sulfonyl fluorides from disulfides under the similar reaction conditions. Sulfonyl chlorides or sulfonyl bromides were effectively obtained from the reaction of disulfides with 6 equiv of either N-chlorosuccinimide or N-bromosuccinimide in acetonitrile/water (10:1) at room temperature. Some other electrophilic chlorinating or brominating reagents are also able to be used instead of N-chlorosuccinimide or N-bromosuccinimide for the syntheses of sulfonyl halides from disulfides. These reactions of disulfides with electrophilic halogenating reagents are convenient methods to prepare thiosulfonates and sulfonyl halides.     

A Simple and Practical Method for the Oxidation of Thiols to Disulfides at Mild Conditions Without Solvents

Abstract

A green, straightforward, and novel method for the oxidation of thiols to the corresponding disulfides is reported using hydrogen peroxide catalyzed by tetrabutylammonium iodide (TBAI) without solvents at room temperature. The corresponding disulfides were obtained with excellent yields and short reaction times.     

TEMPO visible light photocatalysis: The selective aerobic oxidation of thiols to disulfides

TEMPO(2,2,6,6-tetramethylpipe ridine-1-oxyl) is well-established in orangocatalysis that usually work in synergy with transition-metal catalysis or semiconductor photocatalysis.Here,TEMPO was turned into a visible light photocatalyst to conduct the selective aerobic oxidation of thiols into disulfides.With O_2 as an oxidant,a mild and efficient protocol for the selective oxidation of thiols into disulfides including symmetrical and unsymmetrical ones with 5 mol% of TEPMO as a photocatalyst was developed at room temperature under the irradiation of 460 nm blue LEDs.It was found that a complex formed between TEMPO and thiols underpinned the visible light activity and disulfides were obtained in very high isolated yields.This work suggests that TEMPO takes diverse roles in for photocatalytic selective oxidative transformations with O_2 as the oxidant.