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Article

Regioselective Synthesis of Novel Functionalized Dihydro-1,4-thiaselenin-2-ylsufanyl Derivatives under Phase Transfer Catalysis

by
Andrey S. Filippov
,
Svetlana V. Amosova
,
Alexander I. Albanov
and
Vladimir A. Potapov
*
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Division of The Russian Academy of Sciences, 1 Favorsky Str., 664033 Irkutsk, Russia
*
Author to whom correspondence should be addressed.
Catalysts 2022, 12(8), 889; https://doi.org/10.3390/catal12080889
Submission received: 4 July 2022 / Revised: 7 August 2022 / Accepted: 11 August 2022 / Published: 12 August 2022
(This article belongs to the Special Issue The Influence of Phase Transfer Catalysis (PTC) in the Synthesis of Bioactive Compounds)
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Abstract

:
The regioselective one-pot synthesis of novel functionalized 2,3-dihydro-1,4-thiaselenin-2-ylsufanyl derivatives in high yields based on 2-bromomethyl-1,3-thiaselenole and activated alkenes was developed under phase transfer catalysis conditions. The reactions proceed under mild conditions at room temperature in a regioselective manner with the addition of sodium dihydro-1,4-thiaselenin-2-ylthiolate exclusively at the terminal carbon atom of the double bond of vinyl methyl ketone, alkylacrylates, acrylamide, acrylonitrile, divinyl sulfone, and divinyl sulfoxide. The sodium dihydro-1,4-thiaselenin-2-ylthiolate was generated from 2-[amino(imino)methyl]sulfanyl-2,3-dihydro-1,4-thiaselenine hydrobromide. The latter compound was obtained by the reaction of 2-bromomethyl-1,3-thiaselenole with thiourea, which was accompanied by a rearrangement with ring expansion to the six-membered heterocycle. The obtained 2,3-dihydro-1,4-thiaselenin-2-ylsufanyl derivatives are a novel family of compounds with putative biological activity. The addition products of sodium dihydro-1,4-thiaselenin-2-ylthiolate at one double bond of divinyl sulfone and divinyl sulfoxide, containing vinylsulfonyl and vinylsulfinyl groups, are capable of further addition reactions. A possibility to obtain corresponding alcohol derivatives was shown in the reaction with vinyl methyl ketone.

1. Introduction

The chemistry of organoselenium compounds began to develop intensively after the discovery of selenium as an essential trace element for mammals, including humans [1]. Since then, many new classes of organoselenium compounds have been synthesized and their biological activity has been studied [2,3,4,5,6,7].
A number of organoselenium compounds show glutathione peroxidase-like properties. It is known that glutathione peroxidase is a selenium-containing enzyme that reduces the concentration of peroxide compounds in the human body and thereby reduces the risk of many diseases [2,3,4,5,6,7]. Selenium-containing heterocycles are known to exhibit antitumor, antibacterial, antiviral, and glutathione peroxidase-like activities.
Among organoselenium compounds with biological activity, the leading place is occupied by selenium-containing heterocycles. The selenium heterocycles exhibit diverse biological activities, including antibacterial, antitumor, anti-HIV, anti-inflammatory, antiviral, antiproliferative, and glutathione peroxidase-like properties (Figure 1) [3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20].
Ebselen, a well-known heterocyclic compound, is a novel anti-inflammatory drug with neuroprotective and glutathione peroxidase-like action [8,9,10]. This selenium heterocycle is also used for the cardiovascular disease treatment, as well as for prevention of ischemic stroke and overcoming acute stroke. Ebselen has been shown to inhibit CoV-2 activity and viral replication. Recently, ebselen (in the form of ebselen-containing oral capsules SPI-1005) has been undergoing clinical trials in COVID-19 patients after gaining FDA clearance [8,9,10]. In addition, ebselen is recommended for the treatment of various disorders and diseases, including arthritis, Meniere’s disease, and cancer (in combination with other drugs).
The involvement of novel electrophilic reagents, selenium dihalides, in the synthesis of selenium heterocycles is an important trend in the chemistry of organoselenium compounds [21,22,23,24,25]. We were the first [21] to use selenium dichloride and dibromide for the synthesis of organoselenium compounds, including selenium heterocycles by cyclization, annulation, transannular addition, annulation–methoxylation, and selenocyclofunctionalization reactions, and these electrophilic reagents showed high efficiency and selectivity [24,25,26,27,28]. Selenium dichloride and dibromide have also been used for the synthesis of selenium heterocycles by other researchers [29,30,31,32,33,34,35,36].
The anchimeric assistance effect of the selenium atom was quantitatively evaluated for the first time by estimation of the rates of nucleophilic substitution reactions in 2,6-dichloro-9-selenabicyclo[3.3.1]nonane, synthesized by the transannular addition of selenium dichloride to cis,cis-1,5-cyclooctadiene [37].
A new organoselenium reagent, 2-bromomethyl-1,3-thiaselenole, was obtained in high yield by a one-pot synthesis from selenium dibromide and divinyl sulfide [38,39]. 2-Bromomethyl-1,3-thiaselenole is a unique, highly reactive reagent exhibiting unusual chemistry in nucleophilic substitution reactions due to the high anchimeric assistance effect of the selenium atom [37]. It was assumed that 2-bromomethyl-1,3-thiaselenole exists in equilibrium with the corresponding seleniranium cation, which largely determines its chemical behavior. In the last decade, we have developed efficient regio- and stereo-selective approaches to novel heterocyclic organochalcogen compounds by reactions of 2-bromomethyl-1,3-thiaselenole with a variety of nucleophilic reagents [38,39,40,41,42,43,44]. The novel families of unsaturated and heterocyclic organoselenium compounds were obtained based on the reactions of this reagent with various sulfur-centered nucleophiles: (Z)-2-[(organylsulfanyl)selanyl]ethenyl vinyl sulfides, bis[(Z)-2-(vinylsulfanyl)ethenyl] diselenide, 2-alkylsulfanyl-2,3-dihydro-1,4-thiaselenines, (Z)-(2-vinylsulfanyl)ethenyl-1-selanyl(N,N-dialkylcarbamo)dithioates, 2,3-dihydro-1,4-thiaselenin-2-ylthiocyanate, 2,3-dihydro-1,4-thiaselenin-2-yl(N,N-dialkylcarbamo)dithioates [38,39,40,41,42,43,44] (Figure 2).
It is worthy to note that dihydro-1,4-thiaselenines represent a very rare family of compounds. Prior to our investigation, only two representatives of dihydro-1,4-thiaselenines were described in the literature: 5-methyl- and 5-ethyl-2,3-dihydro-1,4-thiaselenines were obtained in 60–64% yields by the reaction of 1-(2-chloroethylsulfanyl)-1-alkynes with lithium selenide [43].
It has been established that 1,4-thiaselenines and their analogs exhibit antitumor and antibacterial activity [19,20].

2. Results and Discussion

The aim of this work was to develop the regioselective synthesis of novel functionalized dihydro-1,4-thiaselenin-2-ylsufanyl derivatives based on nucleophilic addition of dihydro-1,4-thiaselenin-2-ylthiolate anion to activated alkenes.
The sodium dihydro-1,4-thiaselenin-2-ylthiolate (3) was generated from 2-[amino(imino)methyl]sulfanyl-2,3-dihydro-1,4-thiaselenine hydrobromide (2) by the action of sodium hydroxide and involved in situ in further nucleophilic addition reactions. The hydrobromide 2 was obtained by the reaction of 2-bromomethyl-1,3-thiaselenole (1) with thiourea, accompanied by a rearrangement with ring expansion from the five-membered heterocycle to the six-membered thiaselenine derivative (Scheme 1).
We made attempts to obtain corresponding thiol from sodium dihydro-1,4-thiaselenin-2-ylthiolate 3 in a two-phase system by acidifying its aqueous solution and separating organic phase. However, the obtained 2,3-dihydro-1,4-thiaselenine-2-thiol 4 always contained some amount of corresponding disulfide, bis(2,3-dihydro-1,4-thiaselenine-2-yl) disulfide (5), even if the synthesis was carried out in inert atmosphere under argon. In an attempt to isolate thiol 4 by column chromatography (silica gel, eluent: hexane), only disulfide 5 was obtained.
We succeeded in describing the spectral characteristics of thiol 4, including 1H- and 13C-NMR data and mass spectrum (there is a molecular ion, m/z 198), but we failed to isolate it in its pure form due to the high ability of this compound to oxidize to disulfide 5 (Scheme 1).
The intermediate sodium dihydro-1,4-thiaselenin-2-ylthiolate 3 also showed the ability to oxidize to disulfide 5. However, we found that this tendency can be sufficiently suppressed by using sodium borohydride together with sodium hydroxide for the procedure of the generation of thiolate 3 from hydrobromide 2. If a certain amount of disulfide 5 is formed during accidental oxidation with air, then this compound is reduced to thiolate 3 under the action of sodium borohydride.
The reaction of 2-bromomethyl-1,3-thiaselenole 1 with thiourea was efficiently carried out at room temperature in acetonitrile, affording compound 2 in quantitative yield (Scheme 1). Hydrobromide 2 was formed as an easily separable precipitate. Acetonitrile was decanted from the precipitate, which was used without isolation in further reactions in the same flask. Traces of acetonitrile remaining in the flask do not reduce the yield of target products. Thus, the procedures for obtaining target products by nucleophilic addition of thiolate 3 to the double bond of activated alkenes, vinyl methyl ketone, alkyl acrylates, acrylamide, acrylonitrile, divinyl sulfone, and divinyl sulfoxide, were implemented as one-pot syntheses based on starting thiaselenole 1 (Scheme 1).
In the preliminary experiments with methyl vinyl ketone, the hydrobromide 2 reacted in homogeneous systems NaOH/NaBH4/water/THF and NaOH/NaBH4/EtOH at room temperature. Under these conditions, alcohol derivative 4-(2,3-dihydro-1,4-thiaselenin-2-ylsulfanyl)-2-butanol (6) was isolated in 82% yield instead of the expected product, containing the ketone group (Scheme 2).
The synthesis of butanol 6 demonstrates the possibility to obtain corresponding alcohol derivatives from vinyl ketones using a similar approach.
It was concluded that the carbonyl function was reduced to the carbinol group by sodium borohydride under homogeneous conditions. However, when we used phase transfer catalysis conditions in the two-phase system: a methylene chloride solution of methyl vinyl ketone, aqueous solution of hydrobromide 2, sodium hydroxide, sodium borohydride, and a phase transfer catalyst, triethylbenzylammonium chloride (TEBAC), the expected product, butanone 7 was obtained in 90% yield (Scheme 2).
The phase transfer catalysis conditions were found to be preferable not only for methyl vinyl ketone, but also for other activated alkenes. The preferred reaction conditions were developed based on studies of the reaction of hydrobromide 2 with methyl and ethyl acrylates (Scheme 3).
The developed conditions include the sequential addition of an aqueous solution of sodium hydroxide and an aqueous NaOH/NaBH4 solution to an aqueous solution of compound 2, followed by the addition of a solution of acrylate (taken in slight excess, 15–20%) in methylene chloride and TEBAC. After 1 h stirring at room temperature, the organic layer was separated, and the residue was additionally extracted with methylene chloride. Removal of the solvent by a rotary evaporator followed by drying the residue in vacuum afforded 3-(2,3-dihydro-1,4-thiaselenin-2-ylsulfanyl)propanoates 8 and 9 in 95% and 91% yields, respectively (Scheme 3). It is important that the products 8 and 9 did not require additional purifications. When carrying out the reaction with methyl and ethyl acrylates under the same conditions, but in the absence of TEBAC, significantly lower yields of the products 8 and 9 were obtained (5–8%).
Other derivatives of acrylic acid, acrylamide and acrylonitrile, were involved in the nucleophilic addition reaction with sodium thiolate 3, generated from hydrobromide 2 under phase transfer catalysis conditions in the NaOH/NaBH4/TEBAC/H2O/CH2Cl2 system (Scheme 4). Unlike other acrylic acid derivatives, acrylamide has a high boiling point, and it is difficult to remove the excess of this reagent under the reduced pressure after finishing the reaction. Therefore, stoichiometric amounts of the reagents were used in the reaction, however, the reaction duration was increased to 5 h to obtain product 10 in high yield (90%).
The reaction with acrylonitrile requires a longer duration (3 h) compared to the synthesis of compounds 8 and 9 (1 h) under the same conditions from acrylates, which, apparently, surpasses acrylonitrile in reactivity in these reactions. The product, propanenitrile 11, was obtained in 91% yield (Scheme 4).
Finally, compounds containing two double bonds, divinyl sulfone and divinyl sulfoxide, were involved in the nucleophilic addition reactions under phase transfer catalysis conditions. Reaction conditions were found that make it possible to selectively obtain products of the nucleophilic addition of sodium thiolate 3 both at one and at two double bonds of divinyl sulfone. A solution of sodium hydroxide and sodium borohydride in water was slowly added dropwise for 2 h to a two-phase mixture: a solution of divinyl sulfone in methylene chloride and an aqueous solution of hydrobromide 2 (equimolar ratio of divinyl sulfone and hydrobromide 2) with stirring at room temperature. Under these conditions, monoadduct, vinyl sulfone 12, was obtained in 80% yield (Scheme 5). Using the same methodology, the reaction of nucleophilic addition of sodium thiolate 3 at one double bond of divinyl sulfoxide was carried out, affording product 13 in 85% yield (Scheme 5).
It is worthy to note that the products 12 and 13, containing vinylsulfonyl and vinylsulfinyl groups, are capable of further addition reactions. When a two-fold molar excess of hydrobromide 2 with respect to divinyl sulfone was used, bis[2-(2,3-dihydro-1,4-thiaselenin-2-ylsulfanyl)ethyl] sulfone (14) was obtained in 88% yield (Scheme 5). Under the same conditions, the reaction with divinyl sulfoxide was complicated by side processes with the formation of a mixture, from which the expected bis-adduct could not be isolated by column chromatography and re-crystallization methods.
It should be emphasized that all these reactions proceed with high regioselectivity with the addition of thiolate 3 exclusively at the terminal carbon atom of the double bond of activated alkenes. The regioselectivity can be explained using Scheme 6, which demonstrates the examples of the nucleophilic addition of sodium thiolate anion 3 to alkenes containing a carbonyl group.
The nucleophilic addition of dihydro-1,4-thiaselenin-2-ylthiolate anion to activated alkenes proceeds as a 1,4-conjugated addition, and the carbonyl (or sulfonyl) group plays an important role in stabilizing the reaction intermediates. It is well-known that the carbonyl group has a high ability to stabilize the negative charge on the adjacent carbon atom. The negative charge is well-stabilized by the carbonyl group in intermediate B due to the mesomeric effect (relevant resonance structures are outlined in Scheme 6). The protonation of intermediate B by water leads to the formation of the products 7–10. There is no such stabilization in intermediate A.
The structural assignments of synthesized compounds were made using 1H-, 13C-, and 77Se-NMR spectroscopy, including two-dimensional experiments (Supplementary Materials containing NMR spectra are available online), mass spectrometry, and confirmed by elemental analysis.
Molecular ions were observed in the mass spectra of the synthesized compounds.
The obtained values of 77Se-NMR chemical shifts of the products 5–14, which are presented in Scheme 1, Scheme 2, Scheme 3, Scheme 4 and Scheme 5, are typical for the 2,3-dihydro-1,4-thiaselenine derivatives [41]. The spin–spin coupling constants between the selenium atom and the sp3-hybridized carbon atom of the methylene group (1JC-Se = 63–65 Hz) and between the selenium atom and the olefinic carbon atom of the =CH group (1JC-Se = 115–117.5 Hz) are observed in the 13C NMR spectra of the products 5–14 and 2. The obtained values (1JC-Se) are characteristic for the direct C–Se coupling constants [44].
Compounds 5, 6, 13, and 14, containing two asymmetric centers, consist of two or more diastereomers, which are manifested themselves in the 13C and 77Se NMR spectra as “doublet signals” (two closely spaced signals instead of one). Compounds 5 and 14 are mixtures of two diastereomers (d,l- and meso-forms, RR/SS and SR/RS) due to the presence of two asymmetric carbon atoms in the symmetrical molecules. Compound 13 contains the sulfoxide group, which is the asymmetric center.

3. Materials and Methods

3.1. General Information

The 1H (400.1 MHz), 13C (100.6 MHz), and 77Se (76.3 MHz) NMR spectra (the spectra can be found in the Supplementary Materials) were recorded on a Bruker DPX-400 spectrometer (Bruker BioSpin GmbH, Rheinstetten, Germany) in CDCl3 or DMSO-d6 solutions and referred to the residual solvent peaks of CDCl3 (δ = 7.27 and 77.0 ppm), DMSO-d6 (δ = 2.50 and 39.5 ppm) (for 1H- and 13C-NMR, respectively), and dimethyl selenide (77Se-NMR).
Mass spectra were recorded on a Shimadzu GCMS-QP5050A (Shimadzu Corporation, Kyoto, Japan) with electron impact (EI) ionization (70 eV). Elemental analysis was performed on a Thermo Scientific Flash 2000 Elemental Analyzer (Thermo Fisher Scientific Inc., Milan, Italy). Melting points were determined on a Kofler Hot-Stage Microscope PolyTherm A apparatus (Wagner & Munz GmbH, München, Germany). The distilled organic solvents and degassed water were used in the syntheses.

3.2. Synthesis of Starting Hydrobromide 2

2-[Amino(imino)methyl]sulfanyl-2,3-dihydro-1,4-thiaselenine hydrobromide (2). A solution of 2-bromomethyl-1,3-thiaselenole 1 (0.244 g, 1 mmol) was added dropwise to a solution of thiourea (0.076 g, 1 mmol) in MeCN (5 mL) with vigorous stirring. The mixture was stirred at room temperature for 8 h. The formed precipitate was filtered off, and dried in vacuo to yield hydrobromide 2 (0.319 g, 100% yield) as a beige powder, mp 135–136 °C.
The hydrobromide 2 was formed as a separable precipitate. Acetonitrile was decanted from the precipitate, which was used in further reactions in the same flask without isolation. Traces of acetonitrile that remain in the flask do not reduce the yields of the target products.
1H NMR (400 MHz, d6-DMSO): δ 3.33 (dd, 2J = 12.7 Hz, 3J = 5.4 Hz, 1H, CHSe), 3.63 (dd, 2J = 12.7 Hz, 3J = 2.3 Hz, 1H, CHSe), 6.56 (d, 3J = 10.1 Hz, 1H, =CHS), 5.70 (br d, 3J = 5.4 Hz, 1H, SCHS), 6.71 (d, 3J = 10.1 Hz, 2JSe-H = 52.2 Hz, 1H, =CHSe), 9.20 (br s, 2H, NH2), 9.35 (br s, 2H, NH2).
13C NMR (100 MHz, d6-DMSO): δ 24.5 (CH2Se, 1JSe-C = 63.9 Hz), 42.1 (SCHS), 111.7 (SeCH=, 1JSe-C = 116.6 Hz), 115.6 (SCH=), 167.0 (SC(NH2)2).
77Se NMR (76.3 MHz, d6-DMSO): δ 152.1.
Anal. Calcd for C5H9BrN2S2Se (320.13): C, 18.76; H, 2.83; N, 8.75; S, 20.03; Se, 24.66%. Found: C, 18.39; H, 2.70; N, 8.60; S, 19.89; Se, 24.73%.

3.3. Synthesis of Thiol 4 and Disulfide 5

A solution of sodium hydroxide (80%, 0.040 g, 0.8 mmol) in water (1 mL) was added dropwise to a solution of compound 2 (0.16 g, 0.5 mmol) in water (1 mL) with stirring at room temperature. The reaction mixture was stirred for 20 min under argon. Then, methylene chloride (3 mL) and ammonium hydrochloride (0.054 g, 1 mmol) were added followed by the addition of a solution of concentrated hydrochloric acid (35%, 0.05 g, 0.5 mmol) in water (1 mL). The mixture was stirred at room temperature for 10 min under argon and the organic layer was separated. The aqueous phase was extracted with methylene chloride (3 mL). The organic phase was dried over CaCl2, the solvent was removed by a rotary evaporator, and the residue was dried in a vacuum, yielding a mixture of thiol 4 (71 mg, 72% yield) and disulfide 5 (21 mg, 22% yield) as a light-yellow oil. Attempted purification of thiol 4 by column chromatography (silica gel, eluent: hexane) led to isolation of disulfide 5 (67 mg, 69% yield).
2,3-Dihydro-1,4-thiaselenine-2-thiol (4). 1H NMR (400 MHz, CDCl3): δ, 2.26 (br s, 1H, SH), 3.18 (dd, 2J = 11.9 Hz, 3J = 8.6 Hz, 1H, CH2Se), 3.48 (dd, 2J = 11.9 Hz, 3J = 2.5 Hz, 1H, CH2Se), 4.43 (dd, 3J = 8.6 Hz, 3J = 2.5 Hz, 1H, SCHS), 6.45 (br s, 2H, CHSe=CHS).
13C NMR (100 MHz, CDCl3): δ, 28.8 (CH2Se), 37.7 (SCHS), 108.7 (SeCH=), 119.7 (SCH=).
MS (EI), m/z (%): 198 (45) [M]+, 165 (48), 138 (41), 103 (50), 85 (100), 58 (61), 45 (40).
Bis(2,3-dihydro-1,4-thiaselenin-2-yl) disulfide(5), a light-yellow oil.
1H NMR: δ 6.53 (d, 1H, =CHSe, 3J = 9.9 Hz, 2JSe-H = 51.6 Hz), 6.51 (d, 1H, =CHSe, 3J = 9.9 Hz, 2JSe-H = 51.6 Hz), 6.41 (d, 2H, =CHS, 3J = 9.9 Hz), 4.68 (dd, 1H, SCHS, 3J = 7.3 Hz, 3J = 2.6 Hz), 4.63 (dd, 1H, SCHS, 3J = 7.3 Hz, 3J = 2.6 Hz), 3.54 (dd, 1H, CHbSe, 2J = 12.1 Hz, 3J = 2.5 Hz), 3.51 (dd, 1H, CH2Se, 2J = 12.4 Hz, 3J = 2.6 Hz), 3.41 (dd, 1H, CHaSe, 2J = 12.4 Hz, 3J = 7.3 Hz), 3.32 (dd, 1H, CH2Se, 2J = 12.1 Hz, 3J = 7.2 Hz).
13C NMR: δ 117.79, 117.52 (SCH=), 111.09, 110.90 (SeCH=, 1JSe-C = 117.5, 116.7 Hz), 49.76, 49.36 (SCHS), 24.09, 24.03 (CH2Se, 1JSe-C = 63.9 Hz). 77Se NMR: δ 180.00, 178.50.
MS: m/z (%): 392 (3) [M]+, 198 (27), 165 (100), 151 (14), 138 (23), 103 (21), 85 (82), 45 (42).
Anal. Calcd for C8H10S4Se2: C, 24.49; H, 2.57; S 32.69; Se 40.25. Found: C, 24.68; H, 2.42; S 32.93; Se 39.89.

3.4. Synthesis of Butanol 6 and Butanone 7

4-(2,3-Dihydro-1,4-thiaselenin-2-ylsulfanyl)-2-butanol (6). A solution of 2-bromomethyl-1,3-thiaselenole 1 (0.122 g, 0.5 mmol) was added dropwise to a solution of thiourea (0.038 g, 0.5 mmol) in MeCN (3 mL) upon vigorous stirring. The mixture was stirred at room temperature for 8 h. Hydrobromide 2 was formed as an easily separable precipitate. Acetonitrile was decanted from the precipitate, which was used without isolation in further reactions in the same flask.
A solution of sodium hydroxide (80%, 0.02 g, 0.4 mmol) in water (1 mL) was added dropwise to a solution of compound 2 (0.16 g, 0.5 mmol) in water (1 mL) with stirring at room temperature. After 1 min, a solution of sodium hydroxide (80%, 0.02 g, 0.4 mmol) and of sodium borohydride (0.031 g, 0.8 mmol) in water (1 mL) was added dropwise with stirring and the reaction mixture was stirred for 1 min. Then, a solution of vinyl methyl ketone (0.04 g, 0.57 mmol) in THF (2 mL) was added, and the mixture was stirred at room temperature for 3 h. THF was removed by a rotary evaporator and the residue was extracted with methylene chloride (3 × 8 mL). The organic phase was dried over Na2SO4, the solvent was removed by a rotary evaporator, and the residue was dried in a vacuum, yielding product 6 (111 mg, 82% yield) as a light-yellow oil.
1H NMR (400 MHz, CDCl3): δ 1.22 (d, 3J = 6.1 Hz, 3H, CH3), 1.74–1.79 (m, 2H, CH2CH(O)), 1.93 (br s, 1H, OH) 2.87 (n, 2H, SCH2), 3.22 (dd, 2J = 11.7 Hz, 3J = 9.8 Hz, 1H, CH2Se), 3.40 (dd, 2J = 11.7 Hz, 3J = 2.4 Hz, 1H, CH2Se), 3.94 (q, 2J = 6.1 Hz, 1H, CH(OH)CH3), 4.43 (dd, 3J = 9.8 Hz, 2J = 11.7 Hz, 3J = 2.4 Hz, 1H, SCHS), 6.45 (d, 3J = 9.8 Hz, 1H, =CHS), 6.45 (d, 3J = 9.8 Hz, 2JSeH = 54.0 Hz, 1H, =CHSe).
13C NMR (100 MHz, CDCl3): δ 23.49, 23.51 (CH3), 24.91, 24.94 (SeCH2, 1JSeC = 63.6 Hz), 27.50, 27.54 (CH2C(OH)), 38.47, 38.51 (SCH2), 44.89 (SCHS), 66.64, 66.73 (CH(OH)CH3), 109.60, 109.64 (=CHSe, 1JSeC = 116.9 Hz), 119.85, 119.88 (=CHS).
77Se NMR (76 MHz, CDCl3): δ 233.1.
MS (EI), m/z (%): 270 (13) [M]+, 165 (18), 151 (21), 125 (30), 85 (100).
Anal. Calcd for C8H14OS2Se (269.29): C 35.68; H 5.24; S 23.82; Se 29.32. Found: C 35.72; H 4.83; S 23.91; Se 29.68.
4-(2,3-Dihydro-1,4-thiaselenin-2-ylsulfanyl)-2-butanone (7). A solution of sodium hydroxide (80%, 0.02 g, 0.4 mmol) in water (1 mL) was added dropwise to a solution of compound 2 (0.16 g, 0.5 mmol) in water (1 mL) with stirring at room temperature. After 1 min, a solution of sodium hydroxide (80%, 0.02 g, 0.4 mmol) and of sodium borohydride (0.031 g, 0.8 mmol) in water (1 mL) was added dropwise with stirring and the reaction mixture was stirred for 1 min. Then, a solution of vinyl methyl ketone (0.04 g, 0.57 mmol) in methylene chloride (1 mL) and triethylbenzylammonium chloride (3 mg, 3% mol) was added, and the mixture was stirred at room temperature for 3 h. A lower organic layer was separated, and the residue was additionally extracted with methylene chloride (2 × 5 mL). The organic phase was dried over Na2SO4, the solvent was removed by a rotary evaporator, and the residue was dried in a vacuum, yielding product 3 (120 mg, 90% yield) as a light-yellow oil.
1H NMR (400 MHz, CDCl3): δ 2.15 (s, 3H, CH3), 2.78 (t, 3J = 6.9 Hz, 2H, SCH2), 2.93 (t, 3J = 6.9 Hz, 2H, CH2C(O)), 3.17 (dd, 2J = 11.8 Hz, 3J = 9.1 Hz, 1H, CH2Se), 3.37 (dd, 2J = 11.8 Hz, 3J = 2.6 Hz, 1H, CH2Se), 4.40 (dd, 3J = 9.1 Hz, 2J = 11.8 Hz, 3J = 2.6 Hz, 1H, SCHS), 6.40 (d, 3J = 9.8 Hz, 1H, =CHS), 6.44 (d, 3J = 9.8 Hz, 2JSeH = 54.5 Hz, 1H, =CHSe).
13C NMR (100 MHz, CDCl3): δ 24.6 (CH3), 24.8 (SeCH2, 1JSeC = 63.4 Hz), 29.9 (CH2C(O)), 43.6 (SCH2), 45.1 (SCHS), 109.7 (=CHSe, 1JSeC = 115.6 Hz), 119.6 (=CHS), 206.1 (C=O).
77Se NMR (CDCl3): δ 218.7.
MS (EI), m/z (%): 268 (26) [M]+, 165 (25), 151 (15), 125 (36), 85 (100).
Anal. Calcd for C8H12OS2Se (267.27): C 35.95; H 4.53; S 24.00; Se 29.54. Found: C 35.89; H 4.73; S 24.05; Se 29.06.

3.5. Synthesis of Products 8–11

Methyl 3-(2,3-dihydro-1,4-thiaselenin-2-ylsulfanyl)propanoate (8). A solution of 2-bromomethyl-1,3-thiaselenole 1 (0.122 g, 0.5 mmol) was added dropwise to a solution of thiourea (0.038 g, 0.5 mmol) in MeCN (3 mL) with vigorous stirring. The mixture was stirred at room temperature for 8 h. Hydrobromide 2 was formed as an easily separable precipitate. Acetonitrile was decanted from the precipitate, which was used without isolation in further reactions in the same flask. The precipitate 2 (0.5 mmol) was dissolved in water (1 mL) and used in further reactions. A solution of sodium hydroxide (80%, 0.02 g, 0.4 mmol) in water (1 mL) was added dropwise to a solution of hydrobromide 2 (0.5 mmol) in water (1 mL) with stirring at room temperature. After 1 min, a solution of sodium hydroxide (80%, 0.02 g, 0.4 mmol) and of sodium borohydride (0.031 g, 0.8 mmol) in water (1 mL) was added dropwise with stirring and the reaction mixture was stirred for 1 min. Then, a solution of methyl acrylate (0.052 g, 0.6 mmol) in methylene chloride (1 mL) and triethylbenzylammonium chloride (3 mg, 3% mol) was added, and the mixture was stirred at room temperature for 1 h. A lower organic layer was separated, and the residue was additionally extracted with methylene chloride (2 × 5 mL). The organic phase was dried over Na2SO4, the solvent was removed by a rotary evaporator, and the residue was dried in a vacuum, yielding product 8 (135 mg, 95% yield) as a light-yellow oil.
1H NMR (400 MHz, CDCl3): δ 2.66 (t, 3J = 7.2 Hz, 2H, CH2C(O)), 2.99 (dt, 2J = 13.2 Hz, 3J = 7.2 Hz, 2H, SCH2), 3.18 (dd, 2J = 11.6 Hz, 3J = 9.3 Hz, 1H, CH2Se), 3.38 (dd, 2J = 11.6 Hz, 3J = 2.6 Hz, 1H, CH2Se), 3.66 (s, 3H, CH3), 4.42 (dd, 3J = 9.3 Hz, 2J = 11.6 Hz, 3J = 2.6 Hz, 1H, SCHS), 6.40 (d, 3J = 9.9 Hz, 1H, =CHS), 6.44 (d, 3J = 9.9 Hz, 2JSeH 48.5 Hz, 1H, =CHSe).
13C NMR (100 MHz, CDCl3): δ 24.8 (SeCH2, 1JSeC = 63.7 Hz), 25.8 (CH2C(O)), 34.6 (SCH2), 44.7 (SCHSe), 51.7 (CH3), 109.7 (=CHSe, 1JSeC = 116.7 Hz,), 119.4 (=CHS), 171.8 (CH2C(O)).
77Se NMR (76 MHz, CDCl3): δ 218.9.
MS (EI), m/z (%): 284 (55) [M]+, 165 (63), 145 (97), 125 (35), 85 (100).
Anal. Calcd for C8H12O2S2Se (283.27): C 33.92; H 4.27; S 22.64; Se 27.87%. Found: C 33.82; H 4.32; S 22.48, Se 27.21%.
Ethyl 3-(2,3-dihydro-1,4-thiaselenin-2-ylsulfanyl)propanoate (9), 91% yield (135 mg), a light-yellow oil. The product was obtained under the same conditions as compound 8.
1H NMR (400 MHz, CDCl3): δ 1.24 (t, 3J = 7.3 Hz, 3H, CH3CH2), 2.64 (t, 3J = 7.2 Hz, 2H, CH2C(O)), 3.00 (dt, 2J = 13.2 Hz, 3J = 7.2 Hz, 2H, SCH2), 3.20 (dd, 2J = 11.6 Hz, 3J = 9.4 Hz, 1H, CH2Se), 3.39 (dd, 2J = 11.6 Hz, 3J = 2.3 Hz, 1H, CH2Se), 4.13 (q, 3J = 7.3 Hz, 2H, CH2CH3), 4.43 (dd, 3J = 9.4 Hz, 2J = 11.6 Hz, 3J = 2.3 Hz, 1H, SCHS), 6.41 (d, 3J = 9.7 Hz, 1H, =CHS), 6.45 (d, 3J = 9.7 Hz, 2JSeH 57.1 Hz, 1H, =CHSe).
13C NMR (100 MHz, CDCl3): δ 14.1 (CH3), 24.8 (SeCH2, 1JSeC = 63.4 Hz), 25.9 (CH2C(O)), 34.9 (SCH2), 44.9 (SCHSe), 60.6 (OCH2CH3), 109.7 (=CHSe, 1JSeC = 116.5 Hz), 119.6 (=CHS), 171.3 (CH2C(O)).
77Se NMR (76 MHz, CDCl3): δ 219.3.
MS (EI), m/z (%): 298 (19) [M]+, 165 (33), 151 (10), 125 (35), 85 (100).
Anal. Calcd for C9H14O2S2Se (297.30): C 36.36; H 4.75; S 21.57, Se 25.56%. Found: C 36.52; H 4.72; S 21.44. Se 26.10%.
3-(2,3-Dihydro-1,4-thiaselenin-2-ylsulfanyl)propanamide (10). A solution of sodium hydroxide (80%, 0.02 g, 0.4 mmol) in water (1 mL) was added dropwise to a solution of hydrobromide 2 (0.5 mmol) in water (1 mL) with stirring at room temperature. After 1 min, a solution of sodium hydroxide (80%, 0.02 g, 0.4 mmol) and of sodium borohydride (0.031 g, 0.8 mmol) in water (1 mL) was added dropwise with stirring and the reaction mixture was stirred for 1 min. Then, a solution of acrylamide (0.036 g, 0.5 mmol) in methylene chloride (1 mL) and triethylbenzylammonium chloride (3 mg, 3% mol) was added, and the mixture was stirred at room temperature for 5 h. A lower organic layer was separated, and the residue was additionally extracted with methylene chloride (2 × 5 mL). The organic phase was dried over Na2SO4, the solvent was removed by a rotary evaporator, and the residue was dried in a vacuum, yielding product 10 (121 mg, 90% yield) as a white powder, mp 81–83 °C.
1H NMR (400 MHz, CDCl3): δ 2.60 (t, 3J = 7.1 Hz, 2H, CH2C(O)), 3.07 (dt, 2J = 13.2 Hz, 3J = 7.1 Hz, 2H, SCH2), 3.23 (dd, 2J = 11.7 Hz, 3J = 9.1 Hz, 1H, CH2Se), 3.43 (dd, 2J = 11.7 Hz, 3J = 2.3 Hz, 1H, CH2Se), 4.47 (dd, 3J = 9.1 Hz, 2J = 11.7 Hz, 3J = 2.3 Hz, 1H, SCHS), 5.71 (br s, 1H, NH2), 5.84 (br s, 1H, NH2), 6.44 (d, 3J = 9.8 Hz, 1H, =CHS), 6.48 (d, 3J = 9.8 Hz, 2JSeH 54.9 Hz, 1H, =CHSe).
13C NMR (100 MHz, CDCl3): δ 24.9 (SeCH2, 1JSeC = 64.9 Hz), 26.4 (CH2C(O)), 35.9 (SCH2), 45.0 (SCHSe), 109.8 (=CHSe, 1JSeC = 118.0 Hz), 119.5 (=CHS) 173.5 (CH2C(O)).
77Se NMR (76 MHz, CDCl3): δ 216.7.
MS (EI), m/z (%): 269 (37) [M]+, 165 (100), 145 (85), 125 (6), 85 (87).
Anal. Calcd for C7H11NOS2Se (268.26): C 31.34; H 4.13; N 5.22; S 23.91; Se 29.43%. Found: C 31.50; H 4.19; N 5.18; S 23.68; Se 28.85%.
3-(2,3-Dihydro-1,4-thiaselenin-2-ylsulfanyl)propanenitrile (11), 91% yield (114 mg), a light-yellow oil. The product was obtained under the same conditions as compound 8, but the reaction time was 3 h.
1H NMR (400 MHz, CDCl3): δ 2.75 (t, 3J = 7.4 Hz, 2H, CH2CN), 3.06 (dt, 2J = 13.8 Hz, 3J = 7.4 Hz, 2H, SCH2), 3.22 (dd, 1H, CH2Se, 2J = 11.9 Hz, 3J = 8.7 Hz), 3.49 (dd, 2J = 11.9 Hz, 3J = 2.5 Hz, 1H, CH2Se), 4.51 (dd, 3J = 8.7 Hz, 2J = 11.9 Hz, 3J = 2.5 Hz, 1H, SCHS), 6.43 (d, 3J = 9.5 Hz, 1H, =CHS), 6.52 (d, 3J = 9.5 Hz, 2JSeH 51.8 Hz, 1H, =CHSe).
13C NMR (100 MHz, CDCl3): δ 19.1 (CH2CN), 24.8 (SeCH2, 1JSeC = 64.6 Hz), 26.4 (SCH2), 44.7 (SCHSe), 110.6 (=CHSe, 1JSeC = 116.7 Hz), 117.9 (CN), 118.5 (=CHS).
77Se NMR (76 MHz, CDCl3): δ 213.5.
MS (EI), m/z (%): 251 (50) [M]+, 165 (63), 145 (97), 125 (35), 85 (100).
Anal. Calcd for C7H9NS2Se (250.25): C 33.60; H 3.63; N 5.60; S 25.63; Se 31.55. Found: C 33.80; H 3.39; N 5.56; S 25.58; Se 31.98.

3.6. The Syntheses of Divinyl Sulfone and Sulfoxide Derivatives

2-(2,3-Dihydro-1,4-thiaselenin-2-ylsulfanyl)ethyl vinyl sulfone (12). A solution of divinyl sulfone (0.060 g, 0.5 mmol) in methylene chloride (2 mL) and triethylbenzylammonium chloride (3 mg, 3% mol) was added to a solution of compound 2 (0.16 g, 0.5 mmol) in water (1 mL). A solution of sodium hydroxide (80%, 0.04 g, 0.8 mmol) and of sodium borohydride (0.04 g, 1.1 mmol) in water (5 mL) was added dropwise with stirring at room temperature for 2 h. The reaction mixture was stirred at room temperature for 1 h. The lower organic layer was separated, and the aqueous layer was extracted with methylene chloride (2 × 5 mL). The organic phase was dried over Na2SO4, the solvent was distilled off on a rotary evaporator, and the residue was dried in a vacuum to yield the product (0.126 g, 80% yield) as a white powder, mp 64–66 °C.
1H NMR (400 MHz, CDCl3): δ 3.10–3.16 (m, 2H, SCH2), 3.21 (dd, 2J = 11.8 Hz, 3J = 8.6 Hz, 1H, CH2Se), 3.31–3.37 (m, 2H, CH2S(O)2), 3.45 (dd, 2J = 11.8 Hz, 3J = 2.6 Hz, 1H, CH2Se), 4.45 (dd, 3J = 8.6 Hz, 2J = 11.8 Hz, 3J = 2.6 Hz, 1H, SCHS), 6.25 (d, 3Jcis = 9.9 Hz, 1H, =CH2), 6.42 (d, 3J = 9.9 Hz, 1H, =CHS), 6.50 (d, 3J = 9.9 Hz, 1H, =CHSe), 6.51 (d, 3Jtrans = 16.7 Hz, 1H, =CH2), 6.69 (d, 3Jcis = 9.9 Hz, 3Jtrans = 16.7 Hz, 1H, CH=CH2).
13C NMR (100 MHz, CDCl3): δ 23.3 (SCH2), 24.8 (SeCH2, 1JSeC = 64.3 Hz), 45.1 (SCHS), 54.5 (CH2S(O)2), 110.5 (=CHSe, 1JSeC = 117.2 Hz), 118.7 (=CHS), 131.5 (CH=CH2), 136.0 (CH=CH2).
77Se NMR (76 MHz, CDCl3): δ 215.0.
MS (EI), m/z (%): 316 (15) [M]+, 165 (50), 151 (10), 125 (7), 85 (100).
Anal. Calcd for C8H12O2S3Se (315.34): C 30.47; H 3.84; S 30.51; Se 25.04. Found: C 30.85; H 4.03; S 30.09; Se 25.51.
2-(2,3-Dihydro-1,4-thiaselenin-2-ylsulfanyl)ethyl vinyl sulfoxide (13), 85% yield (127 mg), light-yellow oil. The product was obtained under the same conditions as compound 12.
1H NMR (400 MHz, CDCl3): δ, 2.94 (m, 1H, CH2S(O)), 3.10 (m, 1H, CH2S(O)), 3.14 (m, 2H, SCH2), 3.22 (dd, 2J = 11.1, 3J = 9.4, 1H, CH2Se), 3.45 (dd, 2J = 11.1, 3J = 2.1, 1H, CH2Se), 4.46 (dd, 3J = 9.4, 2J = 11.1, 3J = 2.1, 1H, SCHSe), 6.03 (d, Jcis = 9.8, 1H, =CH2), 6.14 (d, Jtrans = 16.5, 1H, =CH2), 6.42 (d, 3J = 9.8, 1H, =CHS), 6.49 (d, 3J = 9.8, 2JSeH = 56.1, 1H, =CHSe), 6.63 (d, 3Jcis = 9.8, 3Jtrans = 16.5, 1H, CH=CH2).
13C NMR (100 MHz, CDCl3): δ, 22.66, 23.18 (CH2S(O)), 24.76, 24.85 (SeCH2, 1JSeC = 64.2,), 44.83, 45.27 (SCH2), 52.26, 52.52 (SCHS), 110.14, 110.17 (=CHSe, 1JSeC = 116.0,), 118.93, 119.07 (=CHS), 122.76 (CH=CH2), 139.51, 139.58 (CH=CH2).
77Se NMR (CDCl3): δ, 213.9, 215.9.
MS (EI), m/z (%): 300 (12) [M]+, 197(15), 165 (85), 151 (7), 125 (7), 85 (100).
Anal. Calcd for C8H12OS3Se (299.34): C 32.10; H 4.04; S 32.14; Se 26.38. Found: C 31.95; H 4.05; S 32.08; Se 26.81.
Bis[2-(2,3-dihydro-1,4-thiaselenin-2-ylsulfanyl)ethyl] sulfone (14). A solution of sodium hydroxide (80%, 0.066 g, 1.32 mmol) in water (1 mL) was added dropwise to a solution of compound 2 (0.53 g, 1.66 mmol) in water (2 mL) with stirring at room temperature. After 1 min, a solution of sodium hydroxide (80%, 0.066 g, 1.32 mmol) and of sodium borohydride (0.138 g, 3.63 mmol) in water (1 mL) was added dropwise with stirring and the reaction mixture was stirred for 1 min. Then, a solution of divinyl sulfone (0.098 g, 0.83 mmol) in methylene chloride (2 mL) and triethyl benzyl ammonium chloride (3 mg, 3% mol) was added and the mixture was stirred at room temperature for 3 h. The lower organic layer was separated, and the aqueous layer was extracted with methylene chloride (2 × 5 mL). The organic phase was dried over Na2SO4, the solvent was distilled off on a rotary evaporator, and the residue was dried in a vacuum to yield the product (0.375 g, 88% yield) as a white powder, mp 90–92 °C.
1H NMR (400 MHz, CDCl3): δ 3.09 (dt, 2J = 14.0 Hz, 3J = 8.0 Hz, 1H, SCH2), 3.10 (dd, 2J = 12.0 Hz, 3J = 8.3 Hz, 1H, CH2Se), 3.12 (dt, 2J = 14.0 Hz, 3J = 8.0 Hz, 1H, SCH2), 3.34 (t, 3J = 8.0 Hz, 2H, CH2S(O)2), 3.38 (dd, 2J = 12.0 Hz, 3J = 2.4 Hz, 1H, CH2Se), 4.41 (dd, 1H, 3J = 8.3 Hz, 2J = 12.0 Hz, 1H, SCHS), 6.32 (d, 3J = 9.9 Hz, 1H, =CHS), 6.40 (d, 3J = 9.9 Hz, 1H, =CHSe).
13C NMR (100 MHz, CDCl3): δ, 22.94, 22.98 (SCH2), 24.62 (SeCH2, 1JSeC = 63.9 Hz), 44.78 (SCHS), 53.55 (CH2S(O)2), 110.35 (=CHSe, 1JSeC = 115.8 Hz), 118.33, 118.36 (=CHS). 77Se NMR (CDCl3): δ, 214.8, 215.3.
MS (EI), m/z (%): 514 (7) [M]+, 211 (14), 165 (65), 151 (5), 112 (6), 85 (100).
Anal. Calcd for. C12H18O2S5Se2 (512.52). C 28.12; H 3.54; S 31.28; Se 30.81. Found: C 28.52; H 3.55; S 31.57; Se 30.81.

4. Conclusions

The regioselective one-pot synthesis of a novel family of functionalized 2,3-dihydro-1,4-thiaselenin-2-ylsufanyl derivatives in high yields based on 2-bromomethyl-1,3-thiaselenole and activated alkenes was developed under phase transfer catalysis conditions. Alkenes activated with carbonyl, alkoxycarbonyl, amido, nitrile, sulfonyl, and sulfinyl groups were used in these reactions. The reaction of 2-bromomethyl-1,3-thiaselenole with thiourea is accompanied by a rearrangement with ring expansion, leading to the six-membered 2-[amino(imino)methyl]sulfanyl-2,3-dihydro-1,4-thiaselenine hydrobromide. The latter compound was used as a source of sodium dihydro-1,4-thiaselenin-2-ylthiolate, which was generated in situ and involved in nucleophilic addition to activated alkenes: vinyl methyl ketone, alkylacrylates, acrylamide, acrylonitrile, divinyl sulfone, and divinyl sulfoxide under phase transfer catalysis. It is worthy to note that the hydrobromide was formed as a separable precipitate. Acetonitrile was decanted from the precipitate, which was used in further reactions in the same flask without isolation. Traces of acetonitrile that remain in the flask do not reduce the yields of the target products. Thus, the procedures for preparation of the target products by nucleophilic addition to a double bond of activated alkenes were realized as the one-pot syntheses based on starting 2-bromomethyl-1,3-thiaselenole.
The obtained 2,3-dihydro-1,4-thiaselenin-2-ylsufanyl derivatives are a novel family of compounds with promising biological activity. They can be used as intermediates for organic synthesis and preparation of novel useful products.

Supplementary Materials

The following supporting information can be downloaded at: www.mdpi.com/article/10.3390/catal12080889/s1, 1H, 13C, and 77Se NMR spectra of the products.

Author Contributions

Investigation and research experiments, A.S.F.; methodology and the data curation, S.V.A.; NMR investigation, A.I.A.; conceptualization and the paper preparation, V.A.P. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Data Availability Statement

Not applicable.

Acknowledgments

The authors thank Baikal Analytical Center SB RAS for providing the instrumental equipment for structural investigations.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Schwarz, K.; Foltz, C.M. Selenium as an integral part of factor 3 against dietary necrotic liver degeneration. J. Am. Chem. Soc. 1957, 79, 3292–3293. [Google Scholar] [CrossRef]
  2. Mugesh, G.; du Mont, W.W.; Sies, H. Chemistry of biologically important synthetic organoselenium compounds. Chem. Rev. 2001, 101, 2125–2179. [Google Scholar] [CrossRef] [PubMed]
  3. Potapov, V.A. Organic diselenides, ditellurides, polyselenides and polytellurides. Synthesis and reactions. In Patai’s Chemistry of Functional Groups. Organic Selenium and Tellurium Compounds; Rappoport, Z., Ed.; John Wiley and Sons: Chichester, UK, 2013; Volume 4, pp. 765–843. [Google Scholar]
  4. Nogueira, C.W.; Zeni, G.; Rocha, J.B.T. Organoselenium and organotellurium compounds: Toxicology and pharmacology. Chem. Rev. 2004, 104, 6255–6286. [Google Scholar] [CrossRef] [PubMed]
  5. Tiekink, E.R.T. Therapeutic potential of selenium and tellurium compounds: Opportunities yet unrealized. Dalton Trans. 2012, 41, 6390–6395. [Google Scholar] [CrossRef]
  6. Braga, A.L.; Rafique, J. Synthesis of biologically relevant small molecules containing selenium. Part B. Anti-infective and anticancer compounds. In Patai’s Chemistry of Functional Groups. Organic Selenium and Tellurium Compounds; Rappoport, Z., Ed.; John Wiley and Sons: Chichester, UK, 2013; Volume 4, pp. 1053–1117. [Google Scholar]
  7. Santi, C. (Ed.) Organoselenium Chemistry: Between Synthesis and Biochemistry; Bentham Science Publishers: Sharjah, United Arab Emirates, 2014; p. 563. [Google Scholar]
  8. Azad, G.K.; Tomar, R.S. Ebselen, a promising antioxidant drug: Mechanisms of action and targets of biological pathways. Mol. Biol. Rep. 2014, 41, 4865–4879. [Google Scholar] [CrossRef] [PubMed]
  9. Jin, Z.; Du, X.; Xu, Y.; Deng, Y.; Liu, M.; Zhao, Y.; Zhang, B.; Li, X.; Zhang, L.; Peng, C.; et al. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature 2020, 582, 289–293. [Google Scholar] [CrossRef]
  10. Weglarz-Tomczak, E.; Tomczak, J.M.; Talma, M.; Burda-Grabowska, M.; Giurg, M.; Brul, S. Identification of ebselen and its analogues as potent covalent inhibitors of papain-like protease from SARS-CoV-2. Sci. Rep. 2021, 11, 3640. [Google Scholar] [CrossRef] [PubMed]
  11. Seliman, A.A.A.; Altaf, M.; Onawole, A.T.; Ahmad, S.; Ahmed, M.Y.; Al-Saadi, A.A.; Altuwaijri, S.; Bhatia, G.; Singh, J.; Isab, A.A. Synthesis, X-ray structures and anticancer activity of gold(I)-carbene complexes with selenones as co-ligands and their molecular docking studies with thioredoxin reductase. J. Organomet. Chem. 2017, 848, 175–183. [Google Scholar] [CrossRef]
  12. Al-Rubaie, A.Z.; Al-Jadaan, S.A.S.; Muslim, S.K.; Saeed, E.A.; Ali, E.T.; Al-Hasani, A.K.J.; Al-Salman, H.N.K.; Al-Fadal, S.A.M. Synthesis, characterization and antibacterial activity of some new ferrocenyl selenazoles and 3,5-diferrocenyl-1,2,4-selenadiazole. J. Organomet. Chem. 2014, 774, 43–47. [Google Scholar] [CrossRef]
  13. Dhau, J.S.; Singh, A.; Singh, A.; Sooch, B.S.; Brandão, P.; Félix, V. Synthesis and antibacterial activity of pyridylselenium compounds: Self-assembly of bis(3-bromo-2-pyridyl)diselenide via intermolecular secondary and π⋯π stacking interactions. J. Organomet. Chem. 2014, 766, 57–66. [Google Scholar] [CrossRef]
  14. Angeli, A.; Tanini, D.; Capperucci, A.; Supuran, C.T. Synthesis of novel selenides bearing benzenesulfonamide moieties as carbonic anhydrase I, II, IV, VII, and IX inhibitors. ASC Med. Chem. Lett. 2017, 8, 1213–1217. [Google Scholar] [CrossRef] [PubMed]
  15. Banerjee, B.; Koketsy, M. Recent developments in the synthesis of biologically relevant selenium-containing scaffolds. Coord. Chem. Rev. 2017, 339, 104–127. [Google Scholar] [CrossRef]
  16. Elsherbini, M.; Hamama, W.S.; Zoorob, H.H. Recent advances in the chemistry of selenium-containing heterocycles: Five-membered ring systems. Coord. Chem. Rev. 2016, 312, 149–177. [Google Scholar] [CrossRef]
  17. Ninomiya, M.; Garud, D.R.; Koketsu, M. Biologically significant selenium-containing heterocycles. Coord. Chem. Rev. 2011, 255, 2968–2990. [Google Scholar] [CrossRef]
  18. Sonawane, A.D.; Sonawane, R.A.; Ninomiya, M.N.; Koketsu, M. Synthesis of seleno-heterocycles via electrophilic/radical cyclization of alkyne containing heteroatoms. Adv. Synth. Catal. 2020, 362, 3485–3515. [Google Scholar] [CrossRef]
  19. Koketsu, M.; Yang, H.; Kim, Y.M.; Ichihash, M.; Ishihara, H. Preparation of 1,4-Oxaselenin from AgNO3/LDA-Assisted Reaction of 3-Selena-4-pentyn-1-one as Potential Antitumor Agents. Organic Lett. 2001, 3, 1705–1707. [Google Scholar] [CrossRef] [PubMed]
  20. Reddy, D.B.; Babu, N.C.; Padmavathi, V.; Padmaja, A. 2-Arylethenyl-2″-Arylethynyl Sulfones: A Potential Source for New Heterocycles. Phosphorus Sulfur Silicon Relat. Elem. 2000, 165, 237–242. [Google Scholar] [CrossRef]
  21. Potapov, V.A.; Amosova, S.V.; Belozerova, O.V.; Albanov, A.I.; Yarosh, O.G.; Voronkov, M.G. Synthesis of 3,6-dihalo-4,4-dimethyl-1,4-selenasilafulvenes. Chem. Heterocycl. Compd. 2003, 39, 549–550. [Google Scholar] [CrossRef]
  22. Abakumov, G.A.; Piskunov, A.V.; Cherkasov, V.K.; Fedushkin, I.L.; Ananikov, V.P.; Eremin, D.B.; Gordeev, E.G.; Beletskaya, I.P.; Averin, A.D.; Bochkarev, M.N.; et al. Organoelement chemistry: Promising growth areas and challenges. Russ. Chem. Rev. 2018, 87, 393–507. [Google Scholar] [CrossRef]
  23. Woollins, J.D.; Laitinen, R.S. (Eds.) Selenium and Tellurium Chemistry. From Small Molecules to Biomolecules and Materials; Springer: Berlin/Heidelberg, Germany, 2011; p. 334. [Google Scholar]
  24. Potapov, V.A.; Musalov, M.V.; Musalova, M.V.; Amosova, S.V. Recent Advances in Organochalcogen Synthesis Based on Reactions of Chalcogen Halides with Alkynes and Alkenes. Curr. Org. Chem. 2016, 20, 136–145. [Google Scholar] [CrossRef]
  25. Musalov, M.V.; Potapov, V.A. Selenium dihalides: New possibilities for the synthesis of selenium-containing heterocycles. Chem. Heterocycl. Comp. 2017, 53, 150–152. [Google Scholar] [CrossRef]
  26. Musalov, M.V.; Yakimov, V.A.; Potapov, V.A.; Amosova, S.V.; Borodina, T.N.; Zinchenko, S.V. A novel methodology for the synthesis of condensed selenium heterocycles based on the annulation and annulation–methoxylation reactions of selenium dihalides. New J. Chem. 2019, 43, 18476–18483. [Google Scholar] [CrossRef]
  27. Potapov, V.A.; Musalov, M.V.; Kurkutov, E.O.; Yakimov, V.A.; Khabibulina, A.G.; Musalova, M.V.; Amosova, S.V.; Borodina, T.N.; Albanov, A.I. Remarkable alkene-to-alkene and alkene-to-alkyne transfer reactions of selenium dibromide and PhSeBr. Stereoselective addition of selenium dihalides to cycloalkenes. Molecules 2020, 25, 194. [Google Scholar] [CrossRef] [PubMed]
  28. Potapov, V.A.; Amosova, S.V.; Abramova, E.V.; Musalov, M.V.; Lyssenko, K.A.; Finn, M.G. 2,6-Dihalo-9-selenabicyclo[3.3.1]nonanes and their complexes with selenium dihalides: Synthesis and structural characterisation. New J. Chem. 2015, 39, 8055–8059. [Google Scholar] [CrossRef]
  29. Kumar, P.; Kashid, V.S.; Mague, J.T.; Balakrishna, M.S. An efficient approach for the synthesis of functionalized selenoethers and selenacalix[4]thiophenes, {2,5-(μ-Se)(3,4-dialkoxythiophene)}4. Tetrahedron Lett. 2014, 55, 5232–5235. [Google Scholar] [CrossRef]
  30. Patra, A.; Bendikov, M.; Chand, S. Poly(3,4-ethylenedioxyselenophene) and Its Derivatives: Novel Organic Electronic Materials. Acc. Chem. Res. 2014, 47, 1465–1474. [Google Scholar] [CrossRef]
  31. Martins, G.M.; Back, D.F.; Kaufman, T.S.; Silveira, C.C. SeCl2-Mediated Approach Toward Indole-Containing Polysubstituted Selenophenes. J. Org. Chem. 2018, 83, 3252–3264. [Google Scholar] [CrossRef]
  32. Braverman, S.; Cherkinsky, M.; Kalendar, Y.; Jana, R.; Sprecher, M.; Goldberg, I. Synthesis of water-soluble vinyl selenides and their high glutathione peroxidase (GPx)-like antioxidant activity. Synthesis 2014, 46, 119–125. [Google Scholar] [CrossRef]
  33. Sarbu, L.G.; Hopf, H.; Jones, P.G.; Birsa, L.M. Selenium halide-induced bridge formation in [2.2]paracyclophanes. Beilstein J. Org. Chem. 2014, 10, 2550–2555. [Google Scholar] [CrossRef] [PubMed]
  34. Arsenyan, P. A simple method for the preparation of selenopheno[3,2-b] and [2,3-b]thiophenes. Tetrahedron Lett. 2014, 55, 2527–2529. [Google Scholar] [CrossRef]
  35. Arsenyan, P.; Petrenko, A.; Belyakov, S. Improved conditions for the synthesis and transformations of aminomethyl selenophenothiophenes. Tetrahedron 2015, 71, 2226–2233. [Google Scholar] [CrossRef]
  36. Volkova, Y.M.; Makarov, A.Y.; Zikirin, S.B.; Genaev, A.M.; Bagryanskaya, I.Y.; Zibarev, A.V. 3,1,2,4-Benzothiaselenadiazine and related heterocycles. Mendeleev Commun. 2017, 27, 19–22. [Google Scholar] [CrossRef]
  37. Accurso, A.A.; Cho, S.-H.; Amin, A.; Potapov, V.A.; Amosova, S.V.; Finn, M.G. Thia-, aza-, and selena[3.3.1]bicyclononane dichlorides: Rates vs. internal nucleophile in anchimeric assistance. J. Org. Chem. 2011, 76, 4392–4395. [Google Scholar] [CrossRef]
  38. Amosova, S.V.; Novokshonova, I.A.; Penzik, M.V.; Filippov, A.S.; Albanov, A.I.; Potapov, V.A. Reaction of 2-bromomethyl-1,3-thiaselenole with thiourea: En route to the first representatives of 2-(organylsulfanyl)-2,3-dihydro-1,4-thiaselenines. Tetrahedron Lett. 2017, 58, 4381–4383. [Google Scholar] [CrossRef]
  39. Amosova, S.V.; Penzik, M.V.; Potapov, V.A.; Filippov, A.S.; Shagun, V.A.; Albanov, A.I.; Borodina, T.N.; Smirnov, V.I. Unexpected Regioselective Reactions of 2-Bromomethyl-1,3-thiaselenole with Dithiocarbamates: The First Example of nucleophilic attack at selenium atom of seleniranium intermediate. Synlett 2016, 27, 1653–1658. [Google Scholar] [CrossRef]
  40. Amosova, S.V.; Filippov, A.A.; Makhaeva, N.A.; Albanov, A.I.; Potapov, V.A. Regio- and stereoselective synthesis of new ensembles of diversely functionalized 1,3-thiaselenol-2-ylmethyl selenides by a double rearrangement reaction. Beilstein J. Org. Chem. 2020, 16, 515–523. [Google Scholar] [CrossRef]
  41. Amosova, S.V.; Filippov, A.S.; Potapov, V.A.; Penzik, M.V.; Makhaeva, N.A.; Albanov, A.I. Regio- and stereoselective synthesis of a novel family of unsaturated compounds with the S–Se bond and their cyclization to 2,3-dihydro-1,4-thiaselenines. Synthesis 2019, 8, 1832–1840. [Google Scholar] [CrossRef]
  42. Amosova, S.V.; Shagun, V.A.; Makhaeva, N.A.; Novokshonova, A.I.; Potapov, V.A. Quantum Chemical and Experimental Studies of an Unprecedented Reaction Pathway of Nucleophilic Substitution of 2-Bromomethyl-1,3-thiaselenole with 1,3-Benzothiazole-2-thiol Proceeding Stepwise at Three Different Centers of Seleniranium Intermediates. Molecules 2021, 26, 6685. [Google Scholar] [CrossRef]
  43. Sukhai, R.S.; Jong, R.; Verkruijsse, H.D.; Brandsma, L. Synthesis of six- and seven-membered heterocycles by reaction of 1-(2-chloroethylthio)-1-alkynes and 1-(3-chloropropylthio)-1-alkynes with alkali metal sulfide, selenide and telluride. Recl. Trav. Chim. Pays-Bas 1981, 100, 368–372. [Google Scholar] [CrossRef]
  44. Duddeck, H. Selenium-77 nuclear magnetic resonance spectroscopy. Prog. Nucl. Magn. Reson. Spectrosc. 1995, 27, 1–323. [Google Scholar] [CrossRef]
Catalysts 12 00889 g001 550
Figure 1. Examples of selenium heterocycles with biological activity.
Figure 1. Examples of selenium heterocycles with biological activity.
Catalysts 12 00889 g001
Catalysts 12 00889 g002 550
Figure 2. The reactions of 2-bromomethyl-1,3-thiaselenole with sulfur-centered nucleophiles.
Figure 2. The reactions of 2-bromomethyl-1,3-thiaselenole with sulfur-centered nucleophiles.
Catalysts 12 00889 g002
Catalysts 12 00889 sch001 550
Scheme 1. Synthesis of 2-[amino(imino)methyl]sulfanyl-2,3-dihydro-1,4-thiaselenine hydrobromide (2), sodium 2,3-dihydro-1,4-thiaselenin-2-ylthiolate (3), 2,3-dihydro-1,4-thiaselenine-2-thiol (4), and bis(2,3-dihydro-1,4-thiaselenine-2-yl) disulfide (5).
Scheme 1. Synthesis of 2-[amino(imino)methyl]sulfanyl-2,3-dihydro-1,4-thiaselenine hydrobromide (2), sodium 2,3-dihydro-1,4-thiaselenin-2-ylthiolate (3), 2,3-dihydro-1,4-thiaselenine-2-thiol (4), and bis(2,3-dihydro-1,4-thiaselenine-2-yl) disulfide (5).
Catalysts 12 00889 sch001
Catalysts 12 00889 sch002 550
Scheme 2. Synthesis of 4-(2,3-dihydro-1,4-thiaselenin-2-ylsulfanyl)-2-butanol (6) and 4-(2,3-dihydro-1,4-thiaselenin-2-ylsulfanyl)-2-butanone (7).
Scheme 2. Synthesis of 4-(2,3-dihydro-1,4-thiaselenin-2-ylsulfanyl)-2-butanol (6) and 4-(2,3-dihydro-1,4-thiaselenin-2-ylsulfanyl)-2-butanone (7).
Catalysts 12 00889 sch002
Catalysts 12 00889 sch003 550
Scheme 3. Synthesis of methyl and ethyl 3-(2,3-dihydro-1,4-thiaselenin-2-ylsulfanyl)propanoates 8 and 9.
Scheme 3. Synthesis of methyl and ethyl 3-(2,3-dihydro-1,4-thiaselenin-2-ylsulfanyl)propanoates 8 and 9.
Catalysts 12 00889 sch003
Catalysts 12 00889 sch004 550
Scheme 4. Synthesis of 3-(2,3-dihydro-1,4-thiaselenin-2-ylsulfanyl)propanamide (10) and 3-(2,3-dihydro-1,4-thiaselenin-2-ylsulfanyl)propanenitrile (11).
Scheme 4. Synthesis of 3-(2,3-dihydro-1,4-thiaselenin-2-ylsulfanyl)propanamide (10) and 3-(2,3-dihydro-1,4-thiaselenin-2-ylsulfanyl)propanenitrile (11).
Catalysts 12 00889 sch004
Catalysts 12 00889 sch005 550
Scheme 5. Synthesis of 3-(2,3-dihydro-1,4-thiaselenin-2-ylsulfanyl)propanamide (10) and 3-(2,3-dihydro-1,4-thiaselenin-2-ylsulfanyl)propanenitrile (11).
Scheme 5. Synthesis of 3-(2,3-dihydro-1,4-thiaselenin-2-ylsulfanyl)propanamide (10) and 3-(2,3-dihydro-1,4-thiaselenin-2-ylsulfanyl)propanenitrile (11).
Catalysts 12 00889 sch005
Catalysts 12 00889 sch006 550
Scheme 6. Explanation of regioselectivity of the nucleophilic addition of sodium dihydro-1,4-thiaselenin-2-ylthiolate 3 to alkenes containing a carbonyl group.
Scheme 6. Explanation of regioselectivity of the nucleophilic addition of sodium dihydro-1,4-thiaselenin-2-ylthiolate 3 to alkenes containing a carbonyl group.
Catalysts 12 00889 sch006
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Filippov, A.S.; Amosova, S.V.; Albanov, A.I.; Potapov, V.A. Regioselective Synthesis of Novel Functionalized Dihydro-1,4-thiaselenin-2-ylsufanyl Derivatives under Phase Transfer Catalysis. Catalysts 2022, 12, 889. https://doi.org/10.3390/catal12080889

AMA Style

Filippov AS, Amosova SV, Albanov AI, Potapov VA. Regioselective Synthesis of Novel Functionalized Dihydro-1,4-thiaselenin-2-ylsufanyl Derivatives under Phase Transfer Catalysis. Catalysts. 2022; 12(8):889. https://doi.org/10.3390/catal12080889

Chicago/Turabian Style

Filippov, Andrey S., Svetlana V. Amosova, Alexander I. Albanov, and Vladimir A. Potapov. 2022. "Regioselective Synthesis of Novel Functionalized Dihydro-1,4-thiaselenin-2-ylsufanyl Derivatives under Phase Transfer Catalysis" Catalysts 12, no. 8: 889. https://doi.org/10.3390/catal12080889

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