Green Organoselenium Chemistry: Selective Syntheses of New 1,4-Thiaselenine Derivatives Based on Reactions of Thiaselenole Reagent with Alcohols and Water

: Environmentally friendly synthetic methods were developed for the selective preparation of new 2,3-dihydro-1,4-thiaselenine derivatives in high yields based on the reactions of 2-bromomethyl-1,3-thiaselenole with alcohols and water at room temperature. The reaction of 2-bromomethyl-1,3-thiaselenole with alcohols was accompanied by a rearrangement with ring extension, leading to six-membered heterocyclic compounds, a new family of 2-organyloxy-2,3-dihydro-1,4-thiaselenines, in 80–96% yields. The remarkable cascade reactions of 2-bromomethyl-1,3-thiaselenole with water afforded 2,3-dihydro-1,4-thiaselenines functionalized with the ( Z )-S-CH=CH-Se fragment and one or two highly reactive aldehyde groups. The latter aldehydes were functionalized by the reactions with alcohols and glycols to give new polyfunctionalized compounds, containing two double bonds, two sulfur atoms, two selenium atoms, and two or four oxygen atoms, in high yields.

Examples of selenium heterocycles with biological activity, including compounds structurally related to 1,4-thiaselenines, are shown in Figure 1.
Previously, we developed the selective one-pot synthesis of 2-bromomethyl-1,3-thiaselenole (1) in 80% yield based on the reaction of selenium dibromide with divinyl sulfide [28,32].All stages of this synthesis, including the formation of five-membered 5-bromo-2-bromomethyl-1,3-thiaselenole followed by dehydrobromination, were realized as a one-pot procedure (Scheme 1).This method made it possible to obtain this reagent with a high purity without using additional purification such as column chromatography [28,32].Previously, we developed the selective one-pot synthesis of 2-bromomethyl-1,3-thiaselenole (1) in 80% yield based on the reaction of selenium dibromide with divinyl sulfide [28,32].All stages of this synthesis, including the formation of five-membered 5-bromo-2-bromomethyl-1,3-thiaselenole followed by dehydrobromination, were realized as a one-pot procedure (Scheme 1).This method made it possible to obtain this reagent with a high purity without using additional purification such as column chromatography [28,32].Thiaselenole 1 is a remarkable highly reactive reagent in which the bromine atom is activated by the strong anchimeric assistance effect of the selenium atom [33].The chemical properties of this reagent show that it exists in equilibrium with seleniranium cation A (Scheme 1) [28][29][30][31], and this is confirmed by quantum chemical calculations [32].The attack of the nucleophiles can proceed at three centers of seleniranium intermediate A [32].
The development of selective syntheses of new 1,4-thiaselenine derivatives using principles of green chemistry and studying chemical properties of these compounds is an important task.
The goal of this research is to develop efficient regioselective syntheses of new 1,4-thiaselenine derivatives based on the reactions of thiaselenole 1 with alcohols and water.The use of green chemistry principles and carrying out reactions under mild conditions (at room temperature) are important features of this research.Some chemical properties of the obtained compounds were also studied.Previously, we developed the selective one-pot synthesis of 2-bromomethyl-1,3-thiaselenole (1) in 80% yield based on the reaction of selenium dibromide with divinyl sulfide [28,32].All stages of this synthesis, including the formation of five-membered 5-bromo-2-bromomethyl-1,3-thiaselenole followed by dehydrobromination, were realized as a one-pot procedure (Scheme 1).This method made it possible to obtain this reagent with a high purity without using additional purification such as column chromatography [28,32].

S Br Br
Scheme 1.The one-pot synthesis of thiaselenole 1 and the equilibrium of thiaselenole 1 with seleniranium cation A.
Thiaselenole 1 is a remarkable highly reactive reagent in which the bromine atom is activated by the strong anchimeric assistance effect of the selenium atom [33].The chemical properties of this reagent show that it exists in equilibrium with seleniranium cation A (Scheme 1) [28][29][30][31], and this is confirmed by quantum chemical calculations [32].The attack of the nucleophiles can proceed at three centers of seleniranium intermediate A [32].
The development of selective syntheses of new 1,4-thiaselenine derivatives using principles of green chemistry and studying chemical properties of these compounds is an important task.
The goal of this research is to develop efficient regioselective syntheses of new 1,4-thiaselenine derivatives based on the reactions of thiaselenole 1 with alcohols and water.The use of green chemistry principles and carrying out reactions under mild conditions (at room temperature) are important features of this research.Some chemical properties of the obtained compounds were also studied.
Scheme 1.The one-pot synthesis of thiaselenole 1 and the equilibrium of thiaselenole 1 with seleniranium cation A.
Thiaselenole 1 is a remarkable highly reactive reagent in which the bromine atom is activated by the strong anchimeric assistance effect of the selenium atom [33].The chemical properties of this reagent show that it exists in equilibrium with seleniranium cation A (Scheme 1) [28][29][30][31], and this is confirmed by quantum chemical calculations [32].The attack of the nucleophiles can proceed at three centers of seleniranium intermediate A [32].
The development of selective syntheses of new 1,4-thiaselenine derivatives using principles of green chemistry and studying chemical properties of these compounds is an important task.
The goal of this research is to develop efficient regioselective syntheses of new 1,4-thiaselenine derivatives based on the reactions of thiaselenole 1 with alcohols and water.The use of green chemistry principles and carrying out reactions under mild conditions (at room temperature) are important features of this research.Some chemical properties of the obtained compounds were also studied.
Along with 1,4-thiaselenine derivatives, compounds with the (Z)-Se-CH=CH-S group were obtained from the studied reactions.It is worth noting that vinyl selenides are versatile intermediates and synthons for the synthesis of both selenium-containing and selenium-free organic compounds [34][35][36][37].Vinyl selenides were used in cross-coupling reactions with terminal alkynes to afford (Z)-and (E)-enyne derivatives in good yields with the retention of the stereoconfiguration of vinyl selenides [38].These compounds were also used in the synthesis of functionalized allyl alcohols and unsaturated aldehydes and ketones [39].Functionalized vinyl selenides show hepatoprotective [40], antinociceptive [41], and antioxidant [42] properties.The synthesis of resveratrol and its derivatives, which exhibit anti-inflammatory, anticancer, antibacterial, and neuroprotective activities, was developed based on vinyl selenides [43].

Results and Discussion
The nucleophilic substitution reaction of thiaselenole 1 with a wide range of alcohols was systematically studied.Alcohols were also used as a reaction medium; they played the role of not only a reagent, but also of a solvent.The reaction proceeded chemo-and regioselectively at room temperature in the presence of sodium bicarbonate for 1-2 h.The reaction was accompanied by a rearrangement with ring extension affording six-membered heterocyclic compounds, a new family of 2-organyloxy-2,3-dihydro-1,4-thiaselenines 2a-k, in high yields (Scheme 2).Sodium bicarbonate acted as a base in this reaction, neutralizing the evolved hydrogen bromide with the formation of sodium bromide.
in good yields with the retention of the stereoconfiguration of vinyl selenides [38].These compounds were also used in the synthesis of functionalized allyl alcohols and unsaturated aldehydes and ketones [39].Functionalized vinyl selenides show hepatoprotective [40], antinociceptive [41], and antioxidant [42] properties.The synthesis of resveratrol and its derivatives, which exhibit anti-inflammatory, anticancer, antibacterial, and neuroprotective activities, was developed based on vinyl selenides [43].

Results and Discussion
The nucleophilic substitution reaction of thiaselenole 1 with a wide range of alcohols was systematically studied.Alcohols were also used as a reaction medium; they played the role of not only a reagent, but also of a solvent.The reaction proceeded chemo-and regioselectively at room temperature in the presence of sodium bicarbonate for 1-2 h.The reaction was accompanied by a rearrangement with ring extension affording six-membered heterocyclic compounds, a new family of 2-organyloxy-2,3-dihydro-1,4-thiaselenines 2a-k, in high yields (Scheme 2).Sodium bicarbonate acted as a base in this reaction, neutralizing the evolved hydrogen bromide with the formation of sodium bromide.
Methoxy and ethoxy derivatives 2a and 2b were obtained in 96% yield in pure form and did not require additional purification.With an increase in the length and branching of the carbon chains of the alcohols, a slight decrease in the yield (84-91%) of the products (2c-g) was observed: the reaction of thiaselenole 1 with less nucleophilic benzyl, allyl and propargyl alcohols was carried out for 2 h (instead of the 1 h reaction for compounds 2a-g) affording the products 2i-k in 80-82% yields (Scheme 2).The reaction is highly regioselective and proceeds via the formation of the intermediate seleniranium cation A, in which the nucleophilic attack of the alkoxide anion at the C2 carbon atom occurs with the cleavage of the C2-Se bond (Scheme 3).The rearrangement with the expansion of a five-membered ring to a six-membered cycle affording only 2-organyloxy-2,3-dihydro-1,4-thiaselenines takes place.The formation of five-membered 1,3-thiaselenole derivatives was not observed.Thus, the nucleophilic at-Scheme 2. The synthesis of a new family of 2-organyloxy-2,3-dihydro-1,4-thiaselenines 2a-k.
Methoxy and ethoxy derivatives 2a and 2b were obtained in 96% yield in pure form and did not require additional purification.With an increase in the length and branching of the carbon chains of the alcohols, a slight decrease in the yield (84-91%) of the products (2c-g) was observed: the reaction of thiaselenole 1 with less nucleophilic benzyl, allyl and propargyl alcohols was carried out for 2 h (instead of the 1 h reaction for compounds 2a-g) affording the products 2i-k in 80-82% yields (Scheme 2).
The reaction is highly regioselective and proceeds via the formation of the intermediate seleniranium cation A, in which the nucleophilic attack of the alkoxide anion at the C2 carbon atom occurs with the cleavage of the C2-Se bond (Scheme 3).The rearrangement with the expansion of a five-membered ring to a six-membered cycle affording only 2organyloxy-2,3-dihydro-1,4-thiaselenines takes place.The formation of five-membered 1,3-thiaselenole derivatives was not observed.Thus, the nucleophilic attack of the alkoxide anion does not occur at the C3 carbon atom, which is bound to the bromine atom in thiaselenole 1, and the reaction does not follow the classical pathway.
The 77 Se NMR data of compounds 2a-k are presented in Table 1.A slight downfield shift of the 77 Se NMR signal is observed with an increase in the length of the carbon chain and branching of the alkyl substituent in the alkoxy group (compounds 2a-d).
tack of the alkoxide anion does not occur at the C3 carbon atom, which is bound to the bromine atom in thiaselenole 1, and the reaction does not follow the classical pathway.The 77 Se NMR data of compounds 2a-k are presented in Table 1.A slight downfield shift of the 77 Se NMR signal is observed with an increase in the length of the carbon chain and branching of the alkyl substituent in the alkoxy group (compounds 2a-d).
Table 1. 77 The 77 Se NMR data of compounds 2a-k are presented in Table 1.A slight downfield shift of the 77 Se NMR signal is observed with an increase in the length of the carbon chain and branching of the alkyl substituent in the alkoxy group (compounds 2a-d).
Table 1. 77Se NMR data of the compounds 2a-k.

Compound
Structure 77  The 77 Se NMR data of compounds 2a-k are presented in Table 1.A slight downfield shift of the 77 Se NMR signal is observed with an increase in the length of the carbon chain and branching of the alkyl substituent in the alkoxy group (compounds 2a-d).
Table 1. 77Se NMR data of the compounds 2a-k.

Compound
Structure 77  The 77 Se NMR data of compounds 2a-k are presented in Table 1.A slight downfield shift of the 77 Se NMR signal is observed with an increase in the length of the carbon chain and branching of the alkyl substituent in the alkoxy group (compounds 2a-d).
Table 1. 77Se NMR data of the compounds 2a-k.

Compound
Structure 77 Se NMR, ppm 2a 127.9The 77 Se NMR data of compounds 2a-k are presented in Table 1.A slight downfield shift of the 77 Se NMR signal is observed with an increase in the length of the carbon chain and branching of the alkyl substituent in the alkoxy group (compounds 2a-d).
Table 1. 77Se NMR data of the compounds 2a-k.

Compound
Structure 77 Se NMR, ppm 2a 127.9The 77 Se NMR data of compounds 2a-k are presented in Table 1.A slight downfield shift of the 77 Se NMR signal is observed with an increase in the length of the carbon chain and branching of the alkyl substituent in the alkoxy group (compounds 2a-d).
Table 1. 77Se NMR data of the compounds 2a-k.

Compound
Structure 77 Se NMR, ppm 2a 127.9The 77 Se NMR data of compounds 2a-k are presented in Table 1.A slight downfield shift of the 77 Se NMR signal is observed with an increase in the length of the carbon chain and branching of the alkyl substituent in the alkoxy group (compounds 2a-d).
Table 1. 77Se NMR data of the compounds 2a-k.

Compound
Structure 77 Se NMR, ppm 2a 127.9The 77 Se NMR data of compounds 2a-k are presented in Table 1.A slight downfield shift of the 77 Se NMR signal is observed with an increase in the length of the carbon chain and branching of the alkyl substituent in the alkoxy group (compounds 2a-d).
Table 1. 77Se NMR data of the compounds 2a-k.

Compound
Structure 77 Se NMR, ppm 2a 127.9The 77 Se NMR data of compounds 2a-k are presented in Table 1.A slight downfield shift of the 77 Se NMR signal is observed with an increase in the length of the carbon chain and branching of the alkyl substituent in the alkoxy group (compounds 2a-d).
Table 1. 77Se NMR data of the compounds 2a-k.

Compound
Structure 77 Se NMR, ppm 2a 127.9The 77 Se NMR data of compounds 2a-k are presented in Table 1.A slight downfield shift of the 77 Se NMR signal is observed with an increase in the length of the carbon chain and branching of the alkyl substituent in the alkoxy group (compounds 2a-d).
Table 1. 77Se NMR data of the compounds 2a-k.

Compound
Structure 77   The 77 Se NMR data of compounds 2a-k are presented in Table 1.A slight downfield shift of the 77 Se NMR signal is observed with an increase in the length of the carbon chain and branching of the alkyl substituent in the alkoxy group (compounds 2a-d).
Table 1. 77Se NMR data of the compounds 2a-k.

Compound
Structure 77   The 77 Se NMR data of compounds 2a-k are presented in Table 1.A slight downfield shift of the 77 Se NMR signal is observed with an increase in the length of the carbon chain and branching of the alkyl substituent in the alkoxy group (compounds 2a-d).
Table 1. 77Se NMR data of the compounds 2a-k.

Compound
Structure 77  Increasing the length of the carbon chain from an ethyl to a hexyl substituent has no noticeable effect on the chemical shift (Table 1, products 2b,c,e,g,h).
The bromine atom is in the β-position in respect to both chalcogens, the selenium and sulfur atoms, in thiaselenole 1. Theoretically, a thiiranium cation can be also formed from thiaselenole 1.In this case, the nucleophilic substitution reaction at the carbon atom of the thiiranium cation with the cleavage of the C-S bond would give other products, 3-alkoxy-2,3-dihydro-1,4-thiaselenoles.However, the formation of these products was not observed, even in traces.
It is worth noting that a quantitative assessment of the anchimeric effect of the selenium atom in comparison with the sulfur atom was previously developed [33].It was shown that the anchimeric assistance effect of the selenium atom is more than one order of magnitude higher than the anchimeric effect of the sulfur atom [33].
A remarkable cascade reaction of thiaselenole 1 with water in aqueous DMSO was found (Scheme 4).The reaction of thiaselenole Increasing the length of the carbon chain from an ethyl to a hexyl substituent has no noticeable effect on the chemical shift (Table 1, products 2b,c,e,g,h).
The bromine atom is in the β-position in respect to both chalcogens, the selenium and sulfur atoms, in thiaselenole 1. Theoretically, a thiiranium cation can be also formed from thiaselenole 1.In this case, the nucleophilic substitution reaction at the carbon atom of the thiiranium cation with the cleavage of the C-S bond would give other products, 3-alkoxy-2,3-dihydro-1,4-thiaselenoles.However, the formation of these products was not observed, even in traces.
It is worth noting that a quantitative assessment of the anchimeric effect of the selenium atom in comparison with the sulfur atom was previously developed [33].It was shown that the anchimeric assistance effect of the selenium atom is more than one order of magnitude higher than the anchimeric effect of the sulfur atom [33].
A remarkable cascade reaction of thiaselenole 1 with water in aqueous DMSO was found (Scheme 4).The reaction of thiaselenole The supposed reaction pathways for the formation of compounds 3 and 4 are depicted in Scheme 5.It is known that thiaselenole 1 generates seleniranium cation A, which acts as the intermediate in reactions with nucleophiles [28][29][30][31][32].The reaction of seleniranium intermediate A with water starts as the nucleophilic attack at the carbon atom of the CH-group of cation A and is accompanied by a rearrangement with ring expansion of the five-membered thiaselenole to the six-membered 1,4-thiaselenine heterocycle.The reaction of thiol B with seleniranium cation A leads to compound 4 and hydrogen bromide, which can act as a catalyst for some of these transformations, e.g., for the oxidation of thiol B to disulfane 3.  The supposed reaction pathways for the formation of compounds 3 and 4 are depicted in Scheme 5.It is known that thiaselenole 1 generates seleniranium cation A, which acts as the intermediate in reactions with nucleophiles [28][29][30][31][32].The reaction of seleniranium intermediate A with water starts as the nucleophilic attack at the carbon atom of the CHgroup of cation A and is accompanied by a rearrangement with ring expansion of the five-membered thiaselenole to the six-membered 1,4-thiaselenine heterocycle.The reaction of thiol B with seleniranium cation A leads to compound 4 and hydrogen bromide, which can act as a catalyst for some of these transformations, e.g., for the oxidation of thiol B to disulfane 3. and sulfur atoms, in thiaselenole 1. Theoretically, a thiiranium cation can be also form from thiaselenole 1.In this case, the nucleophilic substitution reaction at the carbon at of the thiiranium cation with the cleavage of the C-S bond would give other produ 3-alkoxy-2,3-dihydro-1,4-thiaselenoles.However, the formation of these products w not observed, even in traces.
It is worth noting that a quantitative assessment of the anchimeric effect of the se nium atom in comparison with the sulfur atom was previously developed [33].It w shown that the anchimeric assistance effect of the selenium atom is more than one ord of magnitude higher than the anchimeric effect of the sulfur atom [33].
A remarkable cascade reaction of thiaselenole 1 with water in aqueous DMSO w found (Scheme 4).The reaction of thiaselenole The supposed reaction pathways for the formation of compounds 3 and 4 are picted in Scheme 5.It is known that thiaselenole 1 generates seleniranium cation which acts as the intermediate in reactions with nucleophiles [28][29][30][31][32].The reaction seleniranium intermediate A with water starts as the nucleophilic attack at the carb atom of the CH-group of cation A and is accompanied by a rearrangement with r expansion of the five-membered thiaselenole to the six-membered 1,4-thiaselenine h erocycle.The reaction of thiol B with seleniranium cation A leads to compound 4 a hydrogen bromide, which can act as a catalyst for some of these transformations, e.g., the oxidation of thiol B to disulfane 3. It was found that the content of compound 4 in the reaction product mixture increases with increasing the water content.It was revealed that 19% of water in DMSO is close to the optimal water content for efficient selective synthesis of compound 4.Under these conditions, product 4 was obtained in 80% yield and did not require additional purification.The formation of dialdehyde compound 3 was not observed in this case (Scheme 6).

Se
Inorganics 2023, 11, x FOR PEER REVIEW 6 of 18 It was found that the content of compound 4 in the reaction product mixture increases with increasing the water content.It was revealed that 19% of water in DMSO is close to the optimal water content for efficient selective synthesis of compound 4.Under these conditions, product 4 was obtained in 80% yield and did not require additional purification.The formation of dialdehyde compound 3 was not observed in this case (Scheme 6).Thus, simple and environmentally friendly synthetic methods were developed for the preparation of the new 2,3-dihydro-1,4-thiaselenine derivatives 3 and 4 functionalized with the (Z)-S-CH=CH-Se fragment and one or two highly reactive aldehyde groups by the cascade reaction of thiaselenole 1 with water at room temperature.
Mild reaction conditions (room temperature, 2 h) and the ease of carrying out these cascade reactions with the formation of polyfunctional O/S/Se-containing products 3 and 4 functionalized with the (Z)-S-CH=CH-Se fragment and a highly reactive aldehyde group makes these compounds promising reagents.The application of these multifunctional reagents can open up new possibilities in the synthesis of O/S/Se-containing linear compounds and heterocycles.
In the present work, the reagents 3 and 4 were used in the synthesis of novel organoselenium compounds by the reactions with alcohols and glycols.
Compound 4 was involved in the reaction with alcohols: methanol, ethanol, butanol and propargyl alcohol.The reaction was carried out in methylene chloride at room temperature in the presence of a catalytic amount of hydrochloric acid.2-[(Z)-2-(2,2-Dialkoxyethylselanyl)ethenylsulfanyl]-2,3-dihydro-1,4-thiaselenines 5a-d, new compounds containing two oxygen, two sulfur, and two selenium atoms, were obtained in 94-97% yield (Scheme 7).Thus, simple and environmentally friendly synthetic methods were developed for the preparation of the new 2,3-dihydro-1,4-thiaselenine derivatives 3 and 4 functionalized with the (Z)-S-CH=CH-Se fragment and one or two highly reactive aldehyde groups by the cascade reaction of thiaselenole 1 with water at room temperature.
Mild reaction conditions (room temperature, 2 h) and the ease of carrying out these cascade reactions with the formation of polyfunctional O/S/Se-containing products 3 and 4 functionalized with the (Z)-S-CH=CH-Se fragment and a highly reactive aldehyde group makes these compounds promising reagents.The application of these multifunctional reagents can open up new possibilities in the synthesis of O/S/Se-containing linear compounds and heterocycles.
In the present work, the reagents 3 and 4 were used in the synthesis of novel organoselenium compounds by the reactions with alcohols and glycols.
It was found that the content of compound 4 in the reaction product mixture increases with increasing the water content.It was revealed that 19% of water in DMSO is close to the optimal water content for efficient selective synthesis of compound 4.Under these conditions, product 4 was obtained in 80% yield and did not require additional purification.The formation of dialdehyde compound 3 was not observed in this case (Scheme 6).Thus, simple and environmentally friendly synthetic methods were developed for the preparation of the new 2,3-dihydro-1,4-thiaselenine derivatives 3 and 4 functionalized with the (Z)-S-CH=CH-Se fragment and one or two highly reactive aldehyde groups by the cascade reaction of thiaselenole 1 with water at room temperature.
Mild reaction conditions (room temperature, 2 h) and the ease of carrying out these cascade reactions with the formation of polyfunctional O/S/Se-containing products 3 and 4 functionalized with the (Z)-S-CH=CH-Se fragment and a highly reactive aldehyde group makes these compounds promising reagents.The application of these multifunctional reagents can open up new possibilities in the synthesis of O/S/Se-containing linear compounds and heterocycles.
In the present work, the reagents 3 and 4 were used in the synthesis of novel organoselenium compounds by the reactions with alcohols and glycols.
Compound 4 was involved in the reaction with alcohols: methanol, ethanol, butanol and propargyl alcohol.The reaction was carried out in methylene chloride at room temperature in the presence of a catalytic amount of hydrochloric acid.2-[(Z)-2-(2,2-Dialkoxyethylselanyl)ethenylsulfanyl]-2,3-dihydro-1,4-thiaselenines 5a-d, new compounds containing two oxygen, two sulfur, and two selenium atoms, were obtained in 94-97% yield (Scheme 7).It is worth noting that the pure products 5a-d were isolated from the reaction mixture and did not require additional purification.
ganics 2023, 11, x FOR PEER REVIEW 7 of It is worth noting that the pure products 5a-d were isolated from the reaction m ture and did not require additional purification.
Glycols such as 1,3-propandiol, 2,3-butandiol, and (Z)-2-butene-1,4-diol were acted with aldehyde 4 in the presence of hydrochloric acid in methylene chloride room temperature to give bicyclic acetals 6a-c in 83%, 80% and 83% yields, respectiv (Scheme 8).Compound 6b, containing two methyl groups in the dioxane cycle, consists of tw diastereomers (cis/trans ~7:5) according to the NMR data.The assignment of cis-a trans-diastereomers was developed and the spectral data for each diastereomer we presented in the experimental part.
The assignment of cis-and trans-diastereomers was carried out based on the NM investigations.Inter alia, the vicinal coupling constant ( 3 JHH) between CH-protons in t trans-diastereomer is greater (7.8 Hz) than in the cis-product (4. 4 Hz).The difference chemical shifts of both methyl and CH protons is larger in trans-diastereomer than in t cis-product.
Compound 3, bearing two aldehyde groups, was involved in the reaction with cohols and glycols at room temperature affording new unsaturated polyfunctionaliz compounds containing two double bonds, two sulfur atoms, two selenium atoms, a four oxygen atoms (Schemes 9 and 10).
Compound 6b, containing two methyl groups in the dioxane cycle, consists of two diastereomers (cis/trans ~7:5) according to the NMR data.The assignment of cis-and transdiastereomers was developed and the spectral data for each diastereomer were presented in the experimental part.
The assignment of cis-and trans-diastereomers was carried out based on the NMR investigations.Inter alia, the vicinal coupling constant ( 3 J HH ) between CH-protons in the trans-diastereomer is greater (7.8 Hz) than in the cis-product (4. 4 Hz).The difference in chemical shifts of both methyl and CH protons is larger in trans-diastereomer than in the cis-product.
Compound 3, bearing two aldehyde groups, was involved in the reaction with alcohols and glycols at room temperature affording new unsaturated polyfunctionalized compounds containing two double bonds, two sulfur atoms, two selenium atoms, and four oxygen atoms (Schemes 9 and 10).
The reaction of compound 3 with methanol led to diacetal compound 7 in 86% yield (Scheme 9).
The developed reactions proceeded with high selectivity under mild reaction conditions (at room temperature) to afford target products in high yields.
The structural assignment of the obtained compounds 2a-k, 3, 4, 5a-d, 6a-c, 7 and 8a,b was carried out based on the NMR investigations and mass spectrometry data and confirmed by an elemental analysis.Molecular ions were observed in the mass spectra of the obtained compounds.

cis-product.
Compound 3, bearing two aldehyde groups, was involved in the reaction with alcohols and glycols at room temperature affording new unsaturated polyfunctionalized compounds containing two double bonds, two sulfur atoms, two selenium atoms, and four oxygen atoms (Schemes 9 and 10).
The reaction of compound 3 with methanol led to diacetal compound 7 in 86% yield (Scheme 9).Bicyclic unsaturated diacetals 8a,b were obtained in 80% and 85% yields, respectively, by the reaction of dialdehyde 3 with 1,3-propandiol and 2,3-butandiol in the presence of hydrochloric acid at room temperature (Scheme 10).The developed reactions proceeded with high selectivity under mild reaction conditions (at room temperature) to afford target products in high yields.
The structural assignment of the obtained compounds 2a-k, 3, 4, 5a-d, 6a-c, 7 and 8a,b was carried out based on the NMR investigations and mass spectrometry data and confirmed by an elemental analysis.Molecular ions were observed in the mass spectra of the obtained compounds.
The (Z)-configuration of the S-CH=CH-Se fragment remained unchanged in the studied reactions.The spin-spin coupling constants ( 3 JH-H) of protons in the linear S-CH=CH-Se group of compounds 3-8 is about 8 Hz.In the 1,4-thiaselenine ring, the values of the spin-spin coupling constants of protons in the S-CH=CH-Se fragment of compounds 2 and 4-6 is about 10 Hz.
The replacement of the organyloxy substituent in position 2 of the 1,4-thiaselenine ring by the organylsulfanyl group leads to a downfield shift of the 77 Se NMR signal of the selenium atom in the cycle from 128-154 ppm (compounds 2a-k) to 221-225 ppm (compounds 3-6a-c).
Elemental analysis was performed on a Thermo Scientific Flash 2000 Elemental Analyzer (Thermo Fisher Scientific Inc., Milan, Italy).The distilled organic solvents and degassed water were used in syntheses.

General
Procedure for the Synthesis of 2-Alkoxy-2,3-Dihydro-1,4-Thiaselenines 2a-k Sodium hydrocarbonate (0.168 g, 2.0 mmol) was added to a solution of thiaselenole 1 (0.244 g, 1.0 mmol) in alcohol (5 mL) and the mixture was stirred for 1-3 h at room temperature.The mixture was filtered and alcohol excess was removed in vacuum.The (Z)-configuration of the S-CH=CH-Se fragment remained unchanged in the studied reactions.The spin-spin coupling constants ( 3 J H-H ) of protons in the linear S-CH=CH-Se group of compounds 3-8 is about 8 Hz.In the 1,4-thiaselenine ring, the values of the spinspin coupling constants of protons in the S-CH=CH-Se fragment of compounds 2 and 4-6 is about 10 Hz.
The replacement of the organyloxy substituent in position 2 of the 1,4-thiaselenine ring by the organylsulfanyl group leads to a downfield shift of the 77 Se NMR signal of the selenium atom in the cycle from 128-154 ppm (compounds 2a-k) to 221-225 ppm (compounds 3-6a-c).
Elemental analysis was performed on a Thermo Scientific Flash 2000 Elemental Analyzer (Thermo Fisher Scientific Inc., Milan, Italy).The distilled organic solvents and degassed water were used in syntheses.

General
Procedure for the Synthesis of 2-Alkoxy-2,3-Dihydro-1,4-Thiaselenines 2a-k Sodium hydrocarbonate (0.168 g, 2.0 mmol) was added to a solution of thiaselenole 1 (0.244 g, 1.0 mmol) in alcohol (5 mL) and the mixture was stirred for 1-3 h at room temperature.The mixture was filtered and alcohol excess was removed in vacuum.Compounds 2c-k were isolated by column chromatography (silica gel 60, 70-230 mesh, eluent: hexane, then chloroform-hexane 1:4).Compounds 2a and 2b were obtained in pure form without the use of column chromatography and did not require additional purification.

Scheme 1 .
Scheme 1.The one-pot synthesis of thiaselenole 1 and the equilibrium of thiaselenole 1 with seleniranium cation A.

Scheme 3 .
Scheme 3. The reaction pathway of the formation of compounds 2a-k.

RScheme 3 .
Scheme 3. The reaction pathway of the formation of compounds 2a-k.

RScheme 3 .
Scheme 3. The reaction pathway of the formation of compounds 2a-k.

RScheme 3 .
Scheme 3. The reaction pathway of the formation of compounds 2a-k.

RScheme 3 .
Scheme 3. The reaction pathway of the formation of compounds 2a-k.

RScheme 3 .
Scheme 3. The reaction pathway of the formation of compounds 2a-k.

2iRScheme 3 .
Scheme 3. The reaction pathway of the formation of compounds 2a-k.

RScheme 3 .
Scheme 3. The reaction pathway of the formation of compounds 2a-k.

RScheme 3 .
Scheme 3. The reaction pathway of the formation of compounds 2a-k.

Scheme 5 .
Scheme 5.The supposed reaction pathways for the formation of compounds 3 and 4.

Scheme 4 .
Scheme 4. The cascade reaction of thiaselenole 1 with water in aqueous DMSO (77 Se NMR data are included).

Scheme 5 .Scheme 5 .
Scheme 5.The supposed reaction pathways for the formation of compounds 3 and 4. Scheme 5.The supposed reaction pathways for the formation of compounds 3 and 4.

Scheme 6 .
Scheme 6.The selective synthesis of compound 4 ( 77 Se NMR data are included).

Scheme 6 .
Scheme 6.The selective synthesis of compound 4 ( 77 Se NMR data are included).

Scheme 6 .
Scheme 6.The selective synthesis of compound 4 ( 77 Se NMR data are included).

Scheme 9 .
Scheme 9.The efficient synthesis of compound 7 ( 77 Se NMR data are included).

Scheme 9 .
Scheme 9.The efficient synthesis of compound 7 ( 77 Se NMR data are included).

Scheme 3. The reaction pathway of the formation of compounds 2a-k. Table 1. 77 Se NMR data of the compounds 2a-k. Compound Structure 77 Se NMR, ppm 2a bromine atom in thiaselenole 1, and
the reaction does not follow the classical pathway.

propargyl _ Scheme 3. The reaction pathway of the formation of compounds 2a-k.
of the alkoxide anion does not occur at the C3 carbon atom, which is bound to the bromine atom in thiaselenole 1, and the reaction does not follow the classical pathway. tack of the alkoxide anion does not occur at the C3 carbon atom, which is bound to the bromine atom in thiaselenole 1, and the reaction does not follow the classical pathway. tack

Se 198.7 ppm Scheme 4.
The cascade reaction of thiaselenole 1 with water in aqueous DMSO (77Se NMR data are included).

Se 198.7 ppm Scheme 4.
The cascade reaction of thiaselenole 1 with water in aqueous DMSO (77Se NMR data included).