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Molecules containing three‐membered heterocycles, including oxiranes (epoxides), thiiranes (episulfides) and aziridines, are considered privileged structures as they serve as key precursors or intermediates for the synthesis of a varied range of organic compounds, such as natural products, mimetics and pharmaceuticals. The principal advantage of this type of heterocycles is their reactivity towards the nucleophilic ring‐opening, which usually occurs in a regioselective manner, resulting in the formation of 1,2‐disubstituted products. When attached to a chiral scaffold, such as a carbohydrate molecule, the ring‐opening process is usually highly diastereoselective. Therefore, these compounds have been extensively employed in the field of carbohydrates for the synthesis of enantiomerically pure modified sugars that are useful as glycobiology tools. This review presents an overview of the recent methodologies developed for the construction of epoxide, thiirane, and aziridine rings from common or modified sugars. Due to their structural similarity to carbohydrates, three‐membered heterocyclic derivatives of cyclitols and carbasugars have been included. All these compounds, and their ring‐opening derivatives have shown to be crucial in the synthesis of glycomimetics, which display diverse biological activities. These include enzyme inhibition, binding to lectin receptors, and more recently, the use as probes for the diagnosis and monitoring of diseases. [ABSTRACT FROM AUTHOR]

Expanding the enzymatic toolbox for the green synthesis of valuable molecules is still of high interest in synthetic chemistry and the pharmaceutical industry. Chiral thiiranes are valuable sulfur‐containing heterocyclic compounds, but relevant methods for their enantioselective synthesis are limited. Herein, we report a biocatalytic thionation strategy for the enantioselective synthesis of thiiranes, which was developed based on the halohydrin dehalogenase (HHDH)‐catalyzed enantioselective ring‐opening reaction of epoxides with thiocyanate and a subsequent nonenzymatic rearrangement process. A novel HHDH was identified and engineered for enantioselective biocatalytic thionation of various aryl‐ and alkyl‐substituted epoxides on a preparative scale, affording the corresponding thiiranes in up to 43 % isolated yield and 98 % ee. Large‐scale synthesis and useful transformations of chiral thiiranes were also performed to demonstrate the utility and scalability of the biocatalytic thionation strategy. [ABSTRACT FROM AUTHOR]

Thiiranes, the corresponding sulfur analogues of epoxides, are less studied and less encountered in literature. This might be due to the limited existing synthetic approaches for their synthesis. Herein, a mild, sustainable and efficient organocatalytic synthesis of thiiranes has been developed. Starting from olefins and utilizing the epoxidation protocol developed in the Kokotos' group, which employs 2,2,2‐trifluoroacetophenone as the organocatalyst and H2O2 as the oxidant, followed by ring opening by thiourea, a variety of thiiranes were synthesized. Both aromatic and aliphatic moieties are well tolerated, leading to thiiranes in moderate to excellent yields. [ABSTRACT FROM AUTHOR]

Herein, we report the first example of enantioselective (2+1) cycloaddition of thioketones with α‐diazo pyrazoleamides for the direct synthesis of tetrasubstituted thiiranes. In the presence of chiral N,N′‐dioxide/cobalt(ΙΙ) complexes (2–5 mol%), excellent efficiency (up to 99 % yield within 15 mins) and high stereoselectivity (up to >19 : 1 dr and 97 % ee) are available. Elaborations of thiiranes via desulfuration have also been conducted to deliver tetrasubstituted olefins. Density functional theory calculations reveal that the reaction initiates from a doublet state cobalt(ΙΙ) carbenoid, which is followed by a quartet cobalt(ΙΙ)‐bound thiocarbonyl ylide pathway. This work provides a route for the selective construction of tetrasubstituted thiiranes and olefins that are otherwise difficult to access. [ABSTRACT FROM AUTHOR]

The synthesis of sulfur‐ and selenium‐containing isosters of triacyl glycerols is herein described. Regioselective fluoride‐induced ring‐opening reaction of suitable substituted thiiranes with bis(trimethyl)silyl selenide, followed by in situ S‐ and Se‐acylation with fatty acid acyl chlorides, enables the one pot synthesis of mixed chalcogeno esters in good yield. The key step of this methodology is the functionalization of S−Si and Se−Si bonds of silyl chalcogenides, generated in situ under mild conditions. A related procedure for the synthesis of functionalized selenides, bearing two thiol ester and two ester moieties, was also developed through a fine tuning of the reaction conditions. The physico‐chemical properties of these novel fatty acid chalcogeno esters have been investigated through DSC, SAXS, WAXS, FTIR and polarized optical microscopy, and compared to those of the common triglycerides in order to highlight the effect of the replacement of oxygen with other chalcogen elements in the polar head of the lipid. [ABSTRACT FROM AUTHOR]

[Display omitted] Polydentate S N O-coordinating proligands were obtained by addition of thioacetic acid to conjugated alkene, or ring-opening of thiiranes with organolithium compounds as the key stages. These S N O- and known S N S- and S O S- coordinating proligands were used for the synthesis of tetrylenes by the reaction with Lappert's tetrylenes E[N(SiMe 3) 2 ] 2 (E = Ge, Sn), giving polymeric, monomeric or dimeric species depending on the type of the ligand. The structure of stannylenes in solution was analysed by 119Sn NMR spectroscopy. [ABSTRACT FROM AUTHOR]

[Display omitted] New S N S-ligands were obtained by consequent ring-opening of substituted thiiranes by lithiated 2,6-lutidine, mono- functionalized S N -ligands having been isolated as the intermediate compounds. The molecular structure of ligand 2,6-Py(CH 2 CH 2 CBn 2 SH) 2 was elucidated by XRD analysis.The reaction of AlMe 3 with S N S-ligands afforded monomeric methyl aluminum complexes which have been tested in ring- opening polymerization of ε caprolactone in bulk. [ABSTRACT FROM AUTHOR]

The mechanism of the reaction of diphenyldiazomethane with thiobenzophenone and related hetaryl thioketones leading to the corresponding tetrasubstituted thiiranes was studied by means of DFT computational methods at the M06‐2X/6‐311+G(d) level of theory. The study showed that the initial step of this conversion is a classic one‐step (3+2) cycloaddition to give 1,3,4‐thiadiazolines in a regioselective manner. These initially formed products undergo a spontaneous extrusion of N2 resulting in the formation of tetraaryl‐substituted thiocarbonyl ylides as reactive intermediates. The calculated parameters of the activation for the subsequent 1,3‐dipolar electrocyclizations are low (ΔG = 10.8–11.9 kcal/mol) and the only products formed in these reactions are the corresponding thiiranes. The alternative pathways leading to thiocarbonyl ylides via stepwise mechanisms involving zwitterionic or biradical nitrogen‐containing intermediates were ruled out. [ABSTRACT FROM AUTHOR]

The 1,3-dipolar cycloaddition of acyclic 2-diazo-1,3-dicarbonyl compounds (DDC) and thioketones preferably occurs with Z,E-conformers and leads to the formation of transient thiocarbonyl ylides in two stages. The thermodynamically favorable further transformation of C=S ylides bearing at least one acyl group is identified as the 1,5-electrocyclization into 1,3-oxathioles. However, in the case of diazomalonates, the dominating process is 1,3-cyclization into thiiranes followed by their spontaneous desulfurization yielding the corresponding alkenes. Finally, carbocyclic diazodiketones are much less reactive under similar conditions due to the locked cyclic structure and are unfavorable for the 1,3-dipolar cycloaddition due to the Z,Z-conformation of the diazo molecule. This structure results in high, positive values of the Gibbs free energy change for the first stage of the cycloaddition process.

A series of 1-alkenyl aryl sulfides was synthesized from thiiranes and diaryliodonium salts in tetrahydrofuran in the presence of potassium tert-butoxide. The proposed reaction mechanism involves generation of benzynes from the diaryliodonium salts in the presence of the base. Then, nucleophilic attack of the benzynes by thiiranes, followed by hydrogen abstraction and ring opening of the generated thiiranium intermediates, provides the sulfides. These sulfides were further oxidized with performic acid to the corresponding sulfones. The current method provides a metal-free and safe method for the preparation of 1-alkenyl aryl sulfides and their sulfones. [ABSTRACT FROM AUTHOR]

Reactions of acetylene glycidyl ethers with butylamine and ethylene diamine lead to the oxirane ring opening according to the Krasusky rule with the formation of acetylene aminoalcohols. In reaction with thiourea the oxygen atom in the ring is replaced by sulfur leading to the corresponding thiiranes in a high yield. The synthesized compounds possess high antimicrobial activity. [ABSTRACT FROM AUTHOR]

The focus of this article is to highlight novel inhibitors and current examples where the use of selective small-molecule inhibitors has been critical in defining the roles of matrix metalloproteinases (MMPs) in disease. Selective small-molecule inhibitors are surgical chemical tools that can inhibit the targeted enzyme; they are the method of choice to ascertain the roles of MMPs and complement studies with knockout animals. This strategy can identify targets for therapeutic development as exemplified by the use of selective small-molecule MMP inhibitors in diabetic wound healing, spinal cord injury, stroke, traumatic brain injury, cancer metastasis, and viral infection. This article is part of a Special Issue entitled: Matrix Metalloproteinases edited by Rafael Fridman. [ABSTRACT FROM AUTHOR]

Novel β-hydroxy-,β-amino- and β-mercapto- dialkyl- and phenyl-alkyl tellurides have been achieved through regioselective ring opening reactions of oxiranes, aziridines and thiiranes with different Te-nucleophiles, including tellurosilanes. Tellurium-125 NMR chemical shifts of selected compounds have been measured. [ABSTRACT FROM AUTHOR]

Acyclic diazodicarbonyl compounds react at room temperature with cycloaliphatic thioketones, e.g. 2,2,4,4-tetramethyl-3-thioxocyclobutanе-1-one and adamantanethione, via a cascade process in which the key step is a 1,5-electrocyclization of the intermediate thiocarbonyl ylide leading to tetrasubstituted spirocyclic 1,3-oxathioles. The most reactive diazodicarbonyl compound was diazoacetylacetone. In the case of dimethyl diazomalonate competitive 1,3-electrocyclization yielded the corresponding thiirane at elevated temperature, which after spontaneous desulfurization produced a tetrasubstituted alkene. To explain the observed temperature dependence of the main reaction product type obtained from dimethyl diazomalonate and 2,2,4,4-tetramethyl-3-thioxocyclobutanе-1-one as well as to verify reversibility of the thiocarbonyl ylide and 1,3-oxathiole interconversion, the calculations of the energy profile for the transformation of 1,3-oxathiole to alkene were performed at the DFT PBE1PBE/6-31G(d) level.

The application of imidazolinium and amidinium salts as soft Lewis acid organocatalysts is described. These salts were suitable catalysts for the activation of unsaturated thioesters in a Diels–Alder reaction and in the ring opening of thiiranes and epoxides. The products were isolated in good yields. The mild catalysts did not cause desulfurization of the products containing a thiol or thiocarbonyl group.

Sulfurization of selected thiiranes such as 2-phenylthiirane (styrene sulfide), 2,3-tetramethylenethiirane (cyclohexene sulfide) and 2-(α-thienyl)thiirane was carried out, leading to sulfur-rich polymers. The activation of the S 8 molecule was initiated by the fluoride anion (F−) delivered by tetrabutylammonium fluoride (TBAF) dissolved in tetrahydrofuran (THF). The opening of the thiirane ring, followed by the copolymerization process, was initiated by the fluoropolysulfide anions (FS x −) generated in situ. The anionic copolymerizations were carried out under mild conditions, below the floor temperature of S 8 (159 °C), and a variable ratio of monomers (thiirane/sulfur) was applied to obtain polysulfides with a diversified sulfur content. Polysulfides were characterized using analytical (elemental analysis, gel permeation chromatography), spectroscopic (Raman spectroscopy, FTIR), and thermal (thermogravimetry (TGA), differential scanning calorimetry (DSC)) methods. Mechanistic interpretation of sulfur transfer in the anionic copolymerization of thiiranes with S 8 , in the presence of the fluoride anion, has been discussed. [Display omitted] • A series of polysulfides derived from thiiranes and elemental sulfur were synthesized. • Polymers with sulfur rank controlled by thiirane/sulfur ratio were obtained. • Structure of obtained copolymers was confirmed by vibrational spectroscopy. • Influence of sulfur rank on thermal stability and phase structure was shown. • Protocol for efficient sulfur waste management was elaborated. [ABSTRACT FROM AUTHOR]

Various epoxides are converted to their corresponding thiiranes in excellent yields with ammonium thiocyanate and thiourea under non-aqueous conditions in the presence of catalytic amounts of Bi(TFA)3 and Bi(OTf)3.

A series of ferrocenyl ketones were obtained via the Friedel–Crafts acylation with mixed anhydrides using ferrocene as a nucleophilic agent or ferrocene carboxylic acid as a precursor of the electrophilic species. The ketones obtained thereby undergo smooth thionation (tetrahydrofuran, 65°C) with Lawesson's reagent. The ferrocenyl thioketones react with diphenyldiazomethane via N2elimination to afford the hitherto unknown ferrocenyl-substituted thiiranes. [ABSTRACT FROM PUBLISHER]

Reaction of (alkoxymethyl)oxiranes with thiourea in methanol has afforded the corresponding thiiranes, and catalyst-free thermal desulfurization of the products has been studied. The major products of desulfurization are alcohols and alkenes, both in the cases of (polyfluoroalkyloxymethyl)thiiranes and their non-fluorinated analogs. Longer alkyl chain in thiiranes favors formation of alcohols over alkenes formation in the course of desulfurization. [ABSTRACT FROM AUTHOR]

Admantanethione smoothly reacted with lithiated methoxyallene at low temperatures yielding the expected allenyl-substituted thiolate, which upon aqueous work-up underwent spontaneous 1,3-cyclization to afford a hitherto unknown methoxy-substituted vinylthiirane derivative. The analogous reaction with adamantanone led to the corresponding allenyl alcohol that can be isolated and--depending on the conditions applied--either be converted into the corresponding vinyloxirane or into the 2,5-dihydrofuran derivative. Sterically more crowded thioketones were also combined with lithiated methoxy-allene, but in these cases competitive 1,5-cyclization leading to isomeric dihydrothiophene derivatives was observed. DFT calculations of model intermediates and products show distinct energy differences of the sulfur and the corresponding oxygen compounds. Desulfurization of the adamantanethione-derived vinylthiirane yielded a methoxysubstituted 1,3-diene that was studied in cycloadditions with electron-deficient dienophiles. Whereas in the case of tetracyanoethylene the corresponding cyclobutane derivative was formed, the reaction with nitrosobenzene provided the expected 1,2-oxazine derivative. By reductive cleavage of the N-O bond this heterocycle was converted into an unsaturated amino alcohol bearing an adamantane moiety. [ABSTRACT FROM AUTHOR]

A series of [1,3]thiazino[3,2- a]benzimidazolium salts modified in the benzene ring by a condensed 1,4-dioxane ring has been prepared. Reaction with epichlorohydrin occurs with recyclization to form derivatives of 3-(2,3-epithiopropyl)benzimidazol-2-one. [ABSTRACT FROM AUTHOR]

Carbenes, Cobalt(II)/N,N'-Dioxide, Thiiranes, Thioketones, -Diazo Compounds Keywords: Carbenes; Cobalt(II)/N,N'-Dioxide; Thiiranes; Thioketones; -Diazo Compounds EN Carbenes Cobalt(II)/N,N'-Dioxide Thiiranes Thioketones -Diazo Compounds 1 1 1 04/27/22 20220502 NES 220502 B Asymmetric Catalysis b Tetrasubstituted thiiranes can be synthesized by an asymmetric catalytic (2+1) cycloaddition of thioketones as reported by Xiaohua Liu, Yun-Dong Wu, Xiaoming Feng et al. in their Research Article (e202201151). [Extracted from the article]

This account summarizes the Njardarson group ring expansion journey from early vinyl oxirane explorations to the latest vinyl oxetane ring expansion discoveries. The evolution of the program and incredible success of Cu(hfacac)2 as catalyst is detailed. Application of these new ring expansion reactions to natural product, pharmaceutical and commodity chemical targets is discussed as well as our intriguing mechanistic journey and interesting entry into the world of chiral counterion catalysis. [ABSTRACT FROM AUTHOR]

Comparative investigations of adhesive composite materials based on thiirane and its oxirane analog are carried out. It is shown that compositions based on thiirane provide for a high rate of adhesion and cohesion strength gain. It is established that the maximal values of the adhesion strength for thiirane are reached at essentially lower concentrations of a curing agent than in the case of oxirane derivatives. [ABSTRACT FROM AUTHOR]

Novel domino processes that involve sequential reactions via iminium ions derived from β-amino thiols or β-amino alcohols were developed to form bisthiazolidines or bisthiiranes, respectively. The heterocycles were synthesized from readily available starting materials, forming four new chemical bonds in one process without the use of metals. The regioselectivity of the transformation could be explained on the basis of calculations of the coefficients of the frontier orbitals. [ABSTRACT FROM AUTHOR]

An efficient method for the conversion of oxiranes to thiiranes by treatment with excess ammonium thiocyanate in aqueous media under reflux or by microwave irradiation is reported. [ABSTRACT FROM AUTHOR]

A highly efficient stereoselective conversion of N-alkyl-5-(acyloxymethyl)-1,3-oxathiolane-2-imines into thiiran-2-ylmethyl alkylcarbamates is described. The reaction is catalyzed by sodium methoxide and proceeds under mild conditions at room temperature in methanol. [ABSTRACT FROM AUTHOR]

It has been shown that the reaction of epichlorhydrin with 3-hydroxybenzimidazo[2,1- b]thiazanium salts leads to recyclization of the thiazanium ring with the formation of substituted 1-(2,3-epithiopropyl)benzimidazol-2-ones in high yield. The proposed method enables the introduction of functional groups unstable in alkaline medium into the structure of thiirane derivatives. [ABSTRACT FROM AUTHOR]

Abstract: A mild, simple and efficient method for the synthesis of thiiranes from epoxides using catalytic amount of HBF4-SiO2 under solvent-free conditions has been developed. Experimental simplicity, simple work-up procedure and solvent-free reaction condition are important features of the present protocol. [Copyright &y& Elsevier]

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The nucleophilic ring opening reactions of epoxides by aliphatic alcohols and water are achieved efficiently in the presence of catalytic amounts of magnesium hydrogensulfate, Mg(HSO4)2, with high degree of regioselectivity. The reactions are chemoselective and many of the other functional groups such as ethereal carbon-oxygen bonds as well as carbon–carbon double bond remain intact under the reaction conditions. Epoxides also react with thiourea or ammonium thiocyanate in the presence of Mg(HSO4)2 to afford the corresponding thiiranes in good to excellent yields. [ABSTRACT FROM AUTHOR]

Two "Mo2O2S2"-based complexes with phosphinoyldithioformate ligands were synthesized from the metathesis reaction of [R2P(O)CS2]− with (Me4N)2[Mo2O2(µ-S)2(Cl)4] to give [Mo2O2(µ-S)2{R2P(O)CS2}2] (1; R = Ph, 2; R = Bn). The complexes were fully characterized, including the X-ray crystal structure for 1. Variable temperatures 31P NMR of 1 and 2 exhibit non-rigid behavior in solution where three and two coordination isomers were present, respectively. The organic substituent on the P atom greatly impacts the complex non-rigid properties and behavior. The catalytic activity of 1 and 2 towards sulfur atom transfer (SAT) using propylene sulfide and cyclohexene sulfide was explored, employing homogeneous reaction conditions at an ambient temperature on the NMR scale. The complexes showed distinctly different properties along with high conversions in short reaction times. A catalytic cycle consistent with the results is proposed. [ABSTRACT FROM AUTHOR]

A simple, efficient, and new method has been developed for the synthesis of thiiranes from epoxides through a one-pot reaction of epoxides with diethyl phosphite in the presence of ammonium acetate or ammonium hydrogen carbonate/sulfur/ and acidic alumina under solvent-free conditions using microwave irradiation. [Copyright &y& Elsevier]

The article focuses on a new one-step method for the preparation of 2,3-dihydrothiazolo[3,2-a]benzimidazole derivatives using the reaction of 2-chlorobenzimidazole with thiiranes 2a-c. 2,3-Dihydrothiazolo[3,2-a]benzimidazoles 3a-c are formed in moderate form upon heating benzimidazole 1 with an equimolar amount of thiiranes 2a-c in the presence of bases in DMF. The use of asymmetric thiiranes 2b and 2c leads to 2-substituted dihydrothiazolobenzimidazoles 3b and 3c.

Metallocarboxypeptidases (MCPs) are involved in many biological processes such as fibrinolysis or inflammation, development, Alzheimer's disease, and various types of cancer. We describe the synthesis and kinetic characterization of a focused library of 22 thiirane- and oxirane-based potential mechanism-based inhibitors, which led to discovery of an inhibitor for the human pro-carboxypeptidase A1. Our structural analyses show that the thiirane-based small-molecule inhibitor penetrates the barrier of the pro-domain to bind within the active site. This binding leads to a chemical reaction that covalently modifies the catalytic Glu270. These results highlight the importance of combined structural, biophysical, and biochemical evaluation of inhibitors in design strategies for the development of spectroscopically nonsilent probes as effective beacons for in vitro , in cellulo , and/or in vivo localization in clinical and industrial applications.

The 1,3-dipolar cycloaddition of acyclic 2-diazo-1,3-dicarbonyl compounds (DDC) and thioketones preferably occurs with Z,E-conformers and leads to the formation of transient thiocarbonyl ylides in two stages. The thermodynamically favorable further transformation of C=S ylides bearing at least one acyl group is identified as the 1,5-electrocyclization into 1,3-oxathioles. However, in the case of diazomalonates, the dominating process is 1,3-cyclization into thiiranes followed by their spontaneous desulfurization yielding the corresponding alkenes. Finally, carbocyclic diazodiketones are much less reactive under similar conditions due to the locked cyclic structure and are unfavorable for the 1,3-dipolar cycloaddition due to the Z,Z-conformation of the diazo molecule. This structure results in high, positive values of the Gibbs free energy change for the first stage of the cycloaddition process.

Acyclic diazodicarbonyl compounds react at room temperature with cycloaliphatic thioketones, e.g. 2,2,4,4-tetramethyl-3-thioxocyclobutanе-1-one and adamantanethione, via a cascade process in which the key step is a 1,5-electrocyclization of the intermediate thiocarbonyl ylide leading to tetrasubstituted spirocyclic 1,3-oxathioles. The most reactive diazodicarbonyl compound was diazoacetylacetone. In the case of dimethyl diazomalonate competitive 1,3-electrocyclization yielded the corresponding thiirane at elevated temperature, which after spontaneous desulfurization produced a tetrasubstituted alkene. To explain the observed temperature dependence of the main reaction product type obtained from dimethyl diazomalonate and 2,2,4,4-tetramethyl-3-thioxocyclobutanе-1-one as well as to verify reversibility of the thiocarbonyl ylide and 1,3-oxathiole interconversion, the calculations of the energy profile for the transformation of 1,3-oxathiole to alkene were performed at the DFT PBE1PBE/6-31G(d) level.