Selenium Dibromide Click Chemistry: The Efficient Synthesis of Novel Selenabicyclo[3.3.1]nonene-2 and -nonane Derivatives.

Highly efficient and convenient methods for the preparation of 35 novel derivatives of 9-selenabicyclo[3.3.1]nonane and 9-selenabicyclo[3.3.1]nonene-2 in high yields based on the adduct of the transannular addition of SeBr2 to 1,5-cyclooctadiene were developed. The methods for the amination of the adduct made it possible to obtain both diamino selenabicyclo[3.3.1]nonane derivatives and their dihydrobromide salts in one step in 88-98% yields. The methods meet the criteria of click chemistry. Compounds with high glutathione peroxidase mimetic activity were found among water-soluble dihydrobromide salts. The selective reaction of 2,6-dibromo-9-selenabicyclo[3.3.1]nonane with acetonitrile to form 6-bromo-9-selenabicyclo[3.3.1]nonene-2 was discovered. The latter compound served as a promising starting material to give rise to the new class of selenabicyclo[3.3.1]nonene-2 derivatives, e.g., 6-alkoxy-9-selenabicyclo[3.3.1]nonenes were obtained in 94-99% yields.

Click Chemistry of Selenium Dihalides: Novel Bicyclic Organoselenium Compounds Based on Selenenylation/Bis-Functionalization Reactions and Evaluation of Glutathione Peroxidase-like Activity.

A number of highly efficient methods for the preparation of novel derivatives of 9-selenabicyclo[3.3.1]nonane in high yields based on selenium dibromide and cis,cis-1,5-cyclooctadiene are reported. The one-pot syntheses of 2,6-diorganyloxy-9-selenabicyclo[3.3.1]nonanes using various O-nucleophiles including alkanols, phenols, benzyl, allyl, and propargyl alcohols were developed. New 2,6-bis(1,2,3-triazol-1-yl)-9-selenabicyclo[3.3.1]nonanes were obtained by the copper-catalyzed 1,3-dipolar cycloaddition of 2,6-diazido-9-selenabicyclo[3.3.1]nonane with unsubstituted gaseous acetylene and propargyl alcohol. The synthesis of 2,6-bis(vinylsulfanyl)-9-selenabicyclo[3.3.1]nonane, based on the generation of corresponding dithiolate anion from bis[amino(iminio)methylsulfanyl]-9-selenabicyclo[3.3.1]nonane dibromide, followed by the nucleophilic addition of the dithiolate anion to unsubstituted acetylene, was developed. The glutathione peroxidase-like activity of the obtained water-soluble products was estimated and compounds with high activity were found. Overall, 2,6-Diazido-9-selenabicyclo[3.3.1]nonane exhibits the highest activity among the obtained compounds.

Selenium Dihalides Click Chemistry: Highly Efficient Stereoselective Addition to Alkynes and Evaluation of Glutathione Peroxidase-Like Activity of Bis(E-2-halovinyl) Selenides.

Highly efficient stereoselective syntheses of novel bis(E-2-chlorovinyl) selenides and bis(E-2-bromovinyl) selenides in quantitative yields by reactions of selenium dichloride and dibromide with alkynes were developed. The reactions proceeded at room temperature as anti-addition giving products exclusively with (E)-stereochemistry. The glutathione peroxidase-like activity of the obtained products was estimated and compounds with high activity were found. The influence of substituents in the products on their glutathione peroxidase-like activity was discussed.

A Regioselective Synthesis of Novel Functionalized Organochalcogen Compounds by Chalcogenocyclofunctionalization Reactions Based on Chalcogen Halides and Natural Products.

The regioselective synthesis of novel functionalized condensed organochalcogen compounds by chalcogenocyclofunctionalization reactions based on chalcogen halides and the natural products thymol and carvacrol has been developed. The reactions of selenium dibromide with allyl thymol and allyl carvacrol proceeded in methylene chloride at room temperature in the presence of NaHCO3 affording bis[(7-isopropyl-4-methyl-2,3-dihydro-1-benzofuran-2-yl)methyl] and bis[(4-isopropyl-7-methyl-2,3-dihydro-1-benzofuran-2-yl)methyl] selenides in 90-92% yield. Similar sulfides were obtained in 70-72% yields by the reaction of sulfur dichloride in chloroform under reflux. Trihalotellanes containing the same organic moieties were synthesized from allyl thymol, allyl carvacrol and tellurium tetrachloride or tetrabromide in quantitative yields. Corresponding functionalized ditellurides were prepared in 91-92% yields by the reduction of the trichlorotellanes with sodium metabisulfite in two-phase solvent system. The comparison of reactivity of sulfur, selenium and tellurium halides in chalcogenocyclofunctionalization and distinguishing features of each reaction were discussed.

Efficient Synthesis of a New Family of 2,6-Disulfanyl-9-selenabicyclo[3.3.1]nonanes.

The efficient synthesis of a new family of 2,6-disulfanyl-9-selenabicyclo[3.3.1]nonanes in high yields has been developed based on 9-selenabicyclo[3.3.1]nonane-2,6-dithiolate anion generated from bis-isothiouronium salt of 2,6-dibromo-9-selenabicyclo[3.3.1]nonane. The derivatives of 2,6-disulfanyl-9-selenabicyclo[3.3.1]nonane containing alkyl, allyl and benzyl moieties have been prepared in 90-99% yields by nucleophilic substitution of 9-selenabicyclo[3.3.1]nonane-2,6-dithiolate anion with alkyl, allyl and benzyl halides. The reaction of nucleophilic addition of 9-selenabicyclo[3.3.1]nonane-2,6-dithiolate anion to alkyl propiolates afforded 2,6-di(vinylsulfanyl)-9-selenabicyclo[3.3.1]nonanes. The conditions for regio- and stereoselective addition of 9-selenabicyclo[3.3.1]nonane-2,6-dithiolate anion to a triple bond of alkyl propiolates have been found. To date, not a single representative of 2,6-disulfanyl-9-selenabicyclo[3.3.1]nonanes has been described in the literature.

(Z,Z)-Selanediylbis(2-propenamides): Novel Class of Organoselenium Compounds with High Glutathione Peroxidase-Like Activity. Regio- and Stereoselective Reaction of Sodium Selenide with 3-Trimethylsilyl-2-propynamides.

The efficient regio- and stereoselective synthesis of (Z,Z)-3,3'-selanediylbis(2-propenamides) in 76-93% yields was developed based on the reaction of sodium selenide with 3-trimethylsilyl-2-propynamides. (Z,Z)-3,3'-Selanediylbis(2-propenamides) are a novel class of organoselenium compounds. To date, not a single representative of 3,3'-selanediylbis(2-propenamides) has been described in the literature. Studying glutathione peroxidase-like properties by a model reaction showed that the activity of the obtained products significantly varies depending on the organic moieties in the amide group. Divinyl selenide, which contains two lipophilic cyclohexyl substituents in the amide group, exhibits very high glutathione peroxidase-like activity and this compound is considerably superior to other products in this respect.

Remarkable Alkene-to-Alkene and Alkene-to-Alkyne Transfer Reactions of Selenium Dibromide and PhSeBr. Stereoselective Addition of Selenium Dihalides to Cycloalkenes.

The original goal of this research was to study stereochemistry of selenium dihalides addition to cycloalkenes and properties of obtained products. Remarkable alkene-to-alkene and alkene-to-alkyne transfer reactions of selenium dibromide and PhSeBr were discovered during this research. The adducts of selenium dibromide with alkenes or cycloalkenes easily exchange SeBr2 with other unsaturated compounds, including acetylenes, at room temperature, in acetonitrile. Similar alkene-to-alkene and alkene-to-alkyne transfer reactions of the PhSeBr adducts with alkenes or cycloalkenes take place. The supposed reaction pathway includes the selenium group transfer from seleniranium species to alkenes or alkynes. It was found that the efficient SeBr2 and PhSeBr transfer reagents are Se(CH2CH2Br)2 and PhSeCH2CH2Br, which liberate ethylene, leading to a shift in equilibrium. The regioselective and stereoselective synthesis of bis(E-2-bromovinyl) selenides and unsymmetrical E-2-bromovinyl selenides was developed based on the SeBr2 and PhSeBr transfer reactions which proceeded with higher selectivity compared to analogous addition reactions of SeBr2 and PhSeBr to alkynes under the same conditions.