Diorganyl Diselenides Research Articles

Iron(III) Chloride/Dialkyl Diselenides‐Promoted Cascade Cyclization of ortho‐Diynyl Benzyl Chalcogenides

AbstractTreatment of ortho‐diynyl benzyl chalcogenides with a mixture of iron(III) chloride and diorganyl diselenides led to functionalized chalcogen isochromene‐fused chalcogenophene derivatives. The reaction parameters were studied and the results indicated that the reaction of ortho‐ diynyl benzyl chalcogenides (0.25 mmol) with iron(III) chloride hexahydrate (2.0 equiv.) and diorganyl diselenide (2 equiv.) at reflux of dichloroethane was the best condition to give the products in 40–83% yields. The results support the idea that a mixture of iron salts and diorganyl diselenides has a dual action, promoting the cyclization and introducing a new functionalization at the 3‐position of isochalcogenochromenes. The methodology was highly regioselective, giving the product via 6‐endo‐dig mode followed by a second cyclization via 5‐endo‐dig mode.magnified image

Oxone®-Promoted One-Pot Synthesis of 1-Aryl-4-(organylselanyl)-1H-pyrazoles

We describe herein an efficient protocol for the one-pot synthesis of 4-organylselanylpyrazoles by direct cyclocondensation and C-H bond selenylation reactions starting from hydrazines, 1,3-diketones and diorganyl diselenides promoted by Oxone®. The products were obtained through a metal catalyst free methodology, under mild conditions, in short reaction times and moderate to excellent yields.

Metal- and photocatalyst-free synthesis of 3-selenylindoles and asymmetric diarylselenides promoted by visible light.

A novel and sustainable procedure was developed for the synthesis of 3-selenylindoles employing diorganyl diselenides and indoles or electron-rich arenes as starting materials. Visible blue light was used to promote the reaction without employing transition metal complexes or organic photocatalysts as sensitizers. Additives such as strong oxidants or bases were not required. Moreover, ethanol was employed as a benign solvent under mild reaction conditions. Through this easy and eco-friendly approach, several 3-selenylindoles and a number of asymmetric diarylselenides were obtained in good to excellent isolated yields.

Silver Catalysis in Organic Synthesis

Studies on an efficient and practical method for the selective synthesis of diorganyl diselenides over diorganyl selenides are presented. Considering the discrepancies between reports on organoselenium compounds, we wanted to establish a tolerable synthetic method for diorganyl diselenides and investigate their characteristics. We optimized reaction conditions for sodium diselenide preparation using selenium, NH2NH2·H2O, and NaOH and, by treating the obtained sodium diselenide with various alkyl or aryl halides, achieved the selective synthesis of diorganyl diselenides in modest to good yields (57–88%) with good reproducibility. We further studied the mechanistic implication, the effects of solvent changes, and the stability of diorganyl diselenides.

Iron(III)‐Promoted Synthesis of 3‐(Organoselanyl)‐1,2‐Dihydroquinolines from Diorganyl Diselenides and N‐Arylpropargylamines by Sequential Carbon‐Carbon and Carbon‐Selenium Bond Formation

AbstractThe iron‐promoted tandem cyclization‐functionalization reaction of N‐arylpropargylamines with diorganyl diselenides was developed for the preparation of 3‐(organoselanyl)‐1,2‐dihydroquinolines. The best result was obtained when the reaction of N‐arylpropargylamines was carried out by the combination of diorganyl diselenides with FeCl3 ⋅ 6H2O in nitromethane at 70 °C. The control experiments strongly support the cooperative relation between the iron salts and diorganyl diselenides and their high reactivity not only to promote the cyclization but also to introduce a functionalization at the 3‐position of dihydroquinolines. The results indicate the existence of an iron/diorganyl diselenide complex, which forms both a cation and an anion of organoselenyl. In an attempt to prove the synthetic application of 3‐(organoselanyl)‐1,2‐dihydroquinolines prepared, we evaluated their use as substrates in the transition metal‐catalyzed cross‐coupling reactions with nucleophiles, such as boronic acids.magnified image

Copper-catalyzed synthesis of 1,3,5-triaryl-4-(organylselanyl)-1H-pyrazoles by one-pot multicomponent reactions

We describe herein our results for the multicomponent synthesis of 1,3,5-triaryl-4-(organylselanyl)pyrazoles by copper-catalyzed cyclocondensation and a direct CH bond selenation reaction of arylhydrazines, chalcones and diorganyl diselenides using catalytic amount of CuBr in acetic acid as solvent at reflux temperature. This methodology proved to be simple and efficient to furnish a range of 4-(organylselanyl)-1H-pyrazoles in moderate to good yields.

Electrophilic Cyclization Involving Carbon-Selenium/Carbon-Halide Bond Formation: Synthesis of 3-Substituted Selenophenes.

The butylselanyl propargyl alcohols reacted with iodine to afford 3-iodoselenophenes. The change of nucleophile position from propargyl to homopropargyl was crucial for the aromatization and formation of selenophene rings. The experiments revealed that bromine and N-bromosuccinimide were not able to cyclize the butylselanyl propargyl alcohols; however, when the bromine source was copper(II) bromide the corresponding 3-bromoselenophenes were obtained in good yields. In addition, the reaction of butylselanyl propargyl alcohols with diorganyl diselenides catalyzed by copper(I) iodide gave the 3-(organoselanyl)selenophenes. The reaction took place with aromatic rings substituted by either electron-donating or -withdrawing groups in the alkynes and propargyl positions. The steric effects of substituents were dominant in determining the yields, whereas electronic effects had only a minor influence. Furthermore, by monitoring the reaction by 1H NMR, we were able to identify the key intermediate, which supported the elaboration of a proposed reaction mechanism. The 3-iodoselenophenes prepared allowed the synthesis of multifunctional selenophenes via application in metal-catalyzed coupling reactions, such as Sonogashira, Ullmann and Suzuki type reactions.

Ultrasound-promoted synthesis of 2-organoselanyl-naphthalenes using Oxone® in aqueous medium as an oxidizing agent.

A green methodology to synthesize 2-organoselanyl-naphthalenes based on the reaction of alkynols with diaryl diselenides is described. The electrophilic species of selenium were generated in situ, by the oxidative cleavage of the Se–Se bond of diaryl diselenides by Oxone® using water as the solvent. The reactions proceeded efficiently under ultrasonic irradiation as an alternative energy source, using a range of alkynols and diorganyl diselenides as starting materials. Through this methodology, the corresponding 2-organoselanyl-naphthalenes were obtained in moderate to good yields (56–94%) and in short reaction times (0.25–2.3 h).

Alternative Metal-Free Synthesis of Diorganoyl Selenides and Tellurides Mediated by Oxone®

We herein describe an alternative metal-free methodology for the synthesis of diorganyl selenides and tellurides mediated by ­Oxone®. The products were obtained in moderate to excellent yields by reactions of diorganyl diselenides or ditellurides with aryl boronic acids mediated by Oxone® with use of EtOH as the solvent. The methodology is applicable to a broad scope of diorganyl dichalcogenides and aryl boronic acids containing electron-rich, electron-poor, and sterically hindered substituents.

Selenomethoxylation of Alkenes Promoted by Oxone®

We describe herein an alternative method for the selenomethoxylation of unactivated alkenes using Oxone® as a stoichiometric oxidant. The electrophilic species of selenium were easily generated in situ by the reaction of diorganyl diselenides with Oxone®. By this efficient and simple approach, β‐methoxy‐selenides were obtained in moderate to excellent yields at room temperature in an open flask, starting from alkenes by using methanol as both nucleophile and solvent. When a mixture of H2O/CH3CN was employed as the solvent, β‐hydroxy‐selenides were selectively obtained under mild conditions.

Copper‐Catalyzed Selective Synthesis of 5‐Selanyl‐imidazo[2,1‐b]thiazoles

AbstractWe describe a selective and direct method to synthesize a wide variety of 5‐selanyl‐imidazo[2,1‐b]thiazoles by copper(I)–catalyzed reaction of imidazo[2,1‐b]thiazoles with diorganyl diselenides. The reactions were carried out in DMSO at 90 °C in air. The methodology was tolerant to differently substituted diorganyl diselenides containing electron‐deficient, electron‐rich, and bulky groups. Still, various imidazo[2,1‐b]thiazoles were used and furnishing the expected products in good to excellent yields. All the products were selectively coupled at 5‐position of the imidazo[2,1‐b]thiazole and no regioisomers were detected.

Copper‐Iodide‐ and Diorganyl‐Diselenide‐Promoted Cyclization of 2‐Alkynylphenols: Alternative Approach to 3‐Organoselanylbenzo[b]furans

This paper describes an alternative method for the synthesis of 3‐organoselanylbenzo[b]furans through the intramolecular cyclization of 2‐alkynylphenols promoted by copper iodide and diorganyl diselenides. The cyclization reactions were carried out at room temperature in the absence of base and under air (open flask). This synthetic approach proved to be efficient with both diorganyl diselenides and 2‐alkynylphenols bearing electron‐neutral, electron‐donating, and electron‐withdrawing substituents. 2‐Phenyl‐3‐phenylselanylbenzo[b]furan was used as a synthetic precursor in organochalcogen–lithium exchange and bromination reactions, allowing the synthesis of functionalized benzo[b]furans in good yields.

A Benzoyl Peroxide/Diphenyl Diselenide Binary System for Functionalization of Alkynes Leading to Alkenyl and Alkynyl Selenides.

Binary systems consisting of benzoyl peroxide (BPO) and diorganyl diselenide are effective in the selective benzoyloxyselenation of internal alkynes to afford the corresponding β-(benzoyloxy)alkenyl selenides in good yields. In contrast to internal alkynes, terminal alkynes undergo a novel C(sp)-H substitution with the phenylseleno group of the BPO/(PhSe)2 system, providing alkynyl selenides in good yields. Both selenation reactions might proceed via benzoyloxy selenide (PhC(O)O-SeAr) as a key intermediate for electrophilic addition to alkynes. The products alkenyl and alkynyl selenides are expected to be useful synthetic intermediates in organic synthesis.

Synthesis of [3-(trimethylsilyl)prop-2-yn-1-yl] selenides

Efficient and selective methods have been developed for the synthesis of previously unknown organyl [3-(trimethylsilyl)prop-2-yn-1-yl] selenides, organyl prop-2-yn-1-yl selenides, and bis[3-(trimethylsilyl) prop-2-yn-1-yl] selenide by reactions of 3-bromo-1-(trimethylsilyl)prop-1-yne with the corresponding organylselenolates and sodium selenide generated from diorganyl diselenides or elemental selenium by the action of sodium tetrahydridoborate.

Ultrasound‐Assisted Synthesis and Antioxidant Activity of 3‐Selanyl‐1 H‐indole and 3‐Selanylimidazo[1,2‐a]pyridine Derivatives

AbstractA simple and rapid method for the selective synthesis of 3‐(organylselanyl)‐1 H‐indoles and 3‐(organylselanyl)imidazo[1,2‐a]pyridines catalyzed by CuI/SeO2 under ultrasound irradiation was developed. This protocol employs a diverse range of 1 H‐indoles or imidazo[1,2‐a]pyridines and diorganyl diselenides to afford the corresponding products selectively in good to excellent yields. Moreover, the antioxidant activity of these compounds was evaluated by using a wide range of in vitro assays, such as 2‐azinobis‐3‐ethylbenzothiazoline‐6‐sulfonic acid (ABTS), 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical, ferric ion reducing antioxidant power (FRAP), and inhibition of reactive species formation in mice cortex. The bioassays revealed that both classes of the newly synthesized organoselenium compounds present antioxidant activity, with emphasis on the 3‐(organylselanyl)‐1 H‐indoles. This pharmacological activity opens a wide range of biological applications where the reduction of oxidative stress is essential.

A simple method for the synthesis of 4-arylselanyl-7-chloroquinolines used as in vitro acetylcholinesterase inhibitors and in vivo memory improvement

We described here an alternative method for the synthesis of 4-arylselanyl-7-chloroquinolines through reactions of 4,7-dichloroquinoline with organylselenols, generated in situ by the reaction of diorganyl diselenides with H3PO2 (50wt% in H2O). These reactions proceeded efficiently at 60°C under N2 atmosphere and are suitable to a range of diorganyl diselenides containing electron-donating and electron-withdrawing groups, affording the corresponding 4-aryl-7-chloroquinolines in high yields. The synthesized compounds were screened for their in vitro acetylcholinesterase (AChE) activity and our results demonstrated that the 7-chloro-4-[(4-fluorophenyl)selanyl]quinoline inhibited the AChE activity and improved memory in mice, making this compound is a potential therapeutic agent for the treatment of Alzheimer disease and other neurodegenerative disorders.

Synthesis of 2‐Organylchalcogenyl–benzo[b]selenophenes: 1‐(2,2‐Dibromovinyl)‐2‐butylselenanylbenzenes as Precursors to Access Alkynes Susceptible to Cyclization

AbstractA convenient synthesis of 1‐(2‐organylchalcogenylethynyl)‐2‐butylselenanylbenzenes was established taking advantage of the selective reaction of 1‐(2,2‐dibromovinyl)‐2‐butylselenanylbenzenes with thiols or diorganyl diselenides. The new 1‐(2‐chalcogenylethynyl)‐2‐butylselenanylbenzenes were prepared in good yields and used as precursors of 2‐organylchalcogenylbenzo[b]selenophenes via electrophilic cyclization using I2, Br2 or PhSeBr as electrophiles. Different classes of new 3‐substituted‐ (3‐iodo, 3‐bromo, 3‐phenylselenanyl) benzo[b]selenophenes were prepared in good yields. The synthetic application of the obtained products was demonstrated employing the benzo[b]selenophenes in Suzuki and Sonogashira cross‐coupling reactions.

Copper‐Catalyzed Carbon‐Nitrogen/Carbon‐Selenium Bonds Formation: Synthesis of 2‐(Organochalcogenyl)‐indolizines

AbstractThe copper‐catalyzed cyclization of propargylpyridines with diorganyl dichalcogenides was applied to the synthesis of 2‐(organochalcogenyl)‐indolizines. A systematic study of the cyclization system revealed that the mutual action between copper(I) iodide and diorganyl dichalcogenides is essential for the formation of indolizines in good yields avoiding the formation of hydrogenated indolizine. The standard reaction conditions were compatible with many functional groups in the substrates, such as methyl, chlorine, fluorine, methoxy and trifluoromethyl. This protocol was efficient with diorganyl diselenides and ditellurides but ineffective with diorganyl disulfides. In addition, the obtained 2‐(organochalcogenyl)‐indolizines were readily transformed into more complex products by reaction with boronic acids using palladium‐catalyzed cross‐coupling conditions.magnified image

Sequential Carbon-Carbon/Carbon-Selenium Bond Formation Mediated by Iron(III) Chloride and Diorganyl Diselenides: Synthesis and Reactivity of 2-Organoselenyl-Naphthalenes.

In this paper, we report an intramolecular cyclization of benzylic-substituted propargyl alcohols promoted by iron(III) chloride and diorganyl diselenides to give 2-organoselenyl-naphthalenes via a sequential carbon-carbon/carbon-selenium bond formation. The present reaction tolerated a wide range of substituents in both propargyl alcohols and diorganyl diselenides to give the desired 2-organoselenyl-naphthalenes in good yields with high selectivity. In addition, O-acyl protected propargyl alcohol and propargyl bromide were also subjected to this protocol giving the corresponding 2-organoselenyl-naphthalenes. We found that dichalcogenide species affected the formation of cyclized products, whereas diorganyl diselenides gave high yields, moderate yields were obtained with diorganyl disulfides, and no product formation was found with diorganyl ditellurides. The key transformations could be attributed to the carbon-carbon triple bond activation of benzylic-substituted propargyl alcohols by a seleniranium ion, antiattack of the electron cloud from the aromatic ring at the activated triple bond, and cyclization via an exclusive 6-endo-dig process. We also found that the corresponding 2-organoselenyl-naphthalenes are suitable substrates to the selenium-lithium exchange reactions followed by trapping with aldehydes affording the corresponding secondary alcohols.

Silver-catalyzed direct selenylation of terminal alkynes through C[sbnd]H bond functionalization

We described herein the use of a silver catalyst in the selenylation of terminal alkynes by direct CH functionalization. These reactions were performed under mild conditions, reacting a range of terminal alkynes with different diorganyl diselenides using AgNO3 (10mol-%) as catalyst in CH2Cl2 at 25°C under air atmosphere. This is an efficient and general cross-coupling reaction and was performed with alkynes and diorganyl diselenides bearing electron-withdrawing and electron-donating groups affording the corresponding selanylalkynes in good to excellent yields.