Electrophilic Selenium Research Articles

Selenium(II)-Nitrogen Exchange (SeNEx)Chemistry: A Good Chemistry Suitable for Nanomole-Scale Parallel Synthesis, DNA-encoded Library Synthesis, and Bioconjugation.

The continuous development of click reactions with new connecting linkage is crucial for advancing the frontiers of click chemistry. Selenium-nitrogen exchange (SeNEx) chemistry, a versatile chemistry in click chemistry, represents an all-encompassing term for nucleophilic substitution events that replace nitrogen at an electrophilic selenium(II) center, enabling the flexible and efficient assembly of linkages around a Se(II) core. Several SeNEx chemistries have been developed inspired by the biochemical reaction between Ebselen and cysteine residue, and demonstrated significant potential in on-plate nanomole-scale parallel synthesis, selenium-containing DNA-encoded library (SeDEL) synthesis, as well as peptide and protein bioconjugation. This concept aims to present the origins, advancements, and applications of selenium(II)-nitrogen exchange (SeNEx) chemistry while also outlining the potential directions for future research in this field.

Synthesis of Selenium-Decorated N-Oxide Isoquinolines: Arylseleninic Acids in Selenocyclization Reactions.

Herein, we describe the use of benzeneseleninic acid derivatives (BSA) as a bench-stable and easy to handle selenium reagent to access 4-(selanyl)isoquinoline-N-oxides through the selenocyclization of o-alkynyl benzaldehyde oximes. The reaction is conducted in refluxing methanol, allowing the thermal generation of electrophilic selenium species in situ. By this new protocol, a library of 19 selenium-decorated N-oxide isoquinolines was accessed in up to 96% yield with an outstanding substrate tolerance and the feasibility to scale it up 10 times (from 0.25 to 2.5 mmol).

In situ formation of the electrophilic phenylselenenyl sulfate triggered by light

Ammonium persulfate is a mild oxidant capable of oxidizing the selenium-selenium bond through thermal activation or under drastic acid catalysis. In this paper we highlight that this reaction can be activated photochemically, starting from diphenyl diselenide in the absence of any organic or and/or metallic photocatalyst or additive. The protocol was applied to a well-known panel of selenoalkoxylation reactions and the obtained results clearly indicate the involvement of an electrophilic selenium reagent.

Metal‐free regioselective selenylation of β‐napthol derivatives promoted by trichloroisocyanuric acid

AbstractA new approach for synthesizing selenylated naphthalene derivatives is described herein, employing trichloroisocyanuric acid (TCCA) as the oxidizing agent. The developed protocol yielded 18 compounds, with yields ranging from 32 % to 90 %. Additionally, the reaction was conducted under mild conditions, utilizing ethanol as the solvent at room temperature, demonstrating good atom economy. The key aspect of the protocol is the in situ generation of electrophilic selenium species through the reaction of diorganyl diselenides and TCCA.

Semipinacol Rearrangement of Cyclopropenylcarbinols for the Synthesis of Highly Substituted Cyclopropanes.

An electrophile-induced semipinacol rearrangement of cyclopropenylcarbinols is reported. This transformation gives access to various polyfunctionalized cyclopropanes under mild metal-free conditions. The scope of the reaction includes iodine, sulfur and selenium electrophiles, aryl and strained ring migrating groups, and diverse substitution patterns on the cyclopropene. The reaction is particularly efficient for the synthesis of small ring-containing spirocycles, which are important rigid three-dimensional building blocks for medicinal chemistry.

Selenium Atom-Polarization Effect Determines TrxR-Specific Recognition of Metallodrugs.

Thioredoxin reductase (TrxR) is highly overexpressed in cancer cells to promote malignant tumor survival. Designing drugs that inhibit TrxR activity is a promising approach to achieve highly effective cancer chemotherapy. However, the selectivity of TrxR inhibitors continue to be a challenge for scientists. In this work, we demonstrate a new strategy to selectively inhibit TrxR through constructing electrophilic center -N-Se(δ+)-N- by using the polarization effect of the selenium atom. The constructed electrophilic center interacts noncovalently with the active motif of TrxR to avoid the interference of other residues in human tissues, thereby selectively inhibiting intracellular TrxR activity. Computational and experimental analysis confirms that the formed electrophilic selenium center preferred to attack the SeC residues in the redox active center of TrxR at the 498 site through strong noncovalent interactions. Both in vitro and in vivo experimental results confirmed that this strategy can significantly improve the anticancer effect. This study may provide a novel route to design highly effective and selective chemotherapeutic drugs.

Trichloroisocyanuric Acid (TCCA): A Suitable Reagent for the Synthesis of Selanyl‐benzo[b]chalcogenophenes

AbstractA new approach for the synthesis of 3‐organoselanyl‐benzo[b]chalcogenophenes promoted by trichloroisocyanuric acid is reported. The reaction was carried out with electrophilic selenium species which were generated in situ by the reaction between trichloroisocyanuric acid and diorganyl diselenides using ethanol as solvent. The developed method uses mild reaction conditions and was efficient for the synthesis of different 3‐organoselanyl‐benzo[b]chalcogenophenes in a good to excellent yields. Analysis of 77Se NMR spectroscopy indicates that the electrophilic PhSeCl was formed in situ and a plausible reaction mechanism was proposed.

Electrosynthesis of β‐Acyloxy‐γ‐Selenyl Amines via Migratory Oxyselenation of N‐Acyl Allylamines

AbstractA metal‐free and external‐oxidant‐free electrosynthesis of β‐acyloxy‐γ‐selenyl amines was developed. The cascade reaction is triggered by anodic oxidative generation of electrophilic selenium cation, followed by electrophilic addition to the unactivated alkene, and successive water promoted intramolecular acyl migration. The reactions gave the products in up to 98% yield with controllable regio‐ and diastereoselectivities. Different chemoselectivity towards cyclization products was also viable with N‐Boc and N‐Cbz substrates. Both batch chemistry and flow chemistry were available for scale‐up synthesis with up to 91% yield.magnified image

Postpolymerization Modification and Topological Structure Design of Poly(vinyl ether)s Based on the Selective Addition Reaction of Electrophilic Selenium Reagent and Divinyl Monomers

Postpolymerization Modification and Topological Structure Design of Poly(vinyl ether)s Based on the Selective Addition Reaction of Electrophilic Selenium Reagent and Divinyl Monomers

TBHP‐Mediated Selenocyclization of N‐Allylbenzamides/Benzthioamides via In‐Situ Generation of “PhSeOH” Species**

AbstractA simple tert‐butyl hydroperoxide (TBHP)‐mediated method has been developed to construct selenated oxazolines/thiazolines under microwave irradiation. The selenocyclization of N‐allylbenzamides/benzthioamides could be achieved owing to the addition of an active electrophilic selenium species, generated in situ from diphenyl diselenide on reacting with TBHP, at their olefinic site. The reaction mechanism was confirmed by intercepting and characterizing all the proposed intermediates by ESI‐QTOF‐MS and NMR study. This method offers several advantages including simpler reaction conditions, shorter reaction time, catalyst‐free, thus rendering a competent alternative to the synthesis of selenated oxazolines/thiazolines in yields of upto 95 %.

Palladium-Catalyzed Cascade 5-endo-dig Cyclization of Ynamides to Form 4-Alkynyloxazolones.

The selective synthesis of 4-alkynyloxazolones and their further applications as substrates to electrophile-promoted nucleophilic cyclization have been developed. The reaction of ynamides with terminal alkynes proceeded smoothly to give 4-alkynyloxazolones in the presence of a catalytic amount of palladium(II) acetate. The products were obtained with the sequential formation of new C-C and C-O bonds via a cascade procedure. The first step involved a carbon-oxygen bond formation, via a 5-endo-dig closure, which was confirmed by X-ray analyses of the crystalline sample. Subsequently, the reaction of 4-alkynyloxazolones with an electrophilic selenium source gave 3-phenylselanyl benzofuran derivatives via an electrophile-promoted nucleophilic cyclization.

Oxyselenocyclization of 2‐Allylphenols for the Synthesis of 2,3‐Dihydrobenzofuran Selenides

AbstractThe reaction between Oxone® and various di(hetero)aryl or alkyl diselenides enables the formation of an electrophilic selenium species in situ capable to induce the oxyselenocyclization of 2‐allylphenols. This versatile and safe protocol was explored to combine two privileged scaffolds into the structure of products: the 2,3‐dihydrobenzofuran core and an organoselenium moiety. Fifteen 2‐[(organoselanyl)methyl]‐2,3‐dihydrobenzofurans were produced, broadening considerably the number of known examples of this hybrid compound. Moreover, preparation of sulfur and tellurium 2,3‐dihydrobenzofurans derivatives was also successfully demonstrated.

Modern Organoselenium Catalysis: Opportunities and Challenges

AbstractOrganoselenium catalysis has attracted increasing interest in recent years. This Cluster highlights recent key advances in this area regarding the functionalization of alkenes, alkynes, and arenes by electrophilic selenium catalysis, selenonium salt catalysis, selenium-based chalcogen-bonding catalysis, and Lewis basic selenium catalysis. These achievements might inspire and help future research.1 Introduction2 Electrophilic Selenium Catalysis3 Selenonium Salt Catalysis4 Selenium-Based Chalcogen-Bond Catalysis5 Lewis Basic Selenide Catalysis6 Conclusion

Living cationic polymerization of vinyl ethers initiated by electrophilic selenium reagents under ambient conditions

We present a living cationic polymerization of vinyl ethers utilizing electrophilic selenium reagents as initiators and pentacarbonylbromomanganese (Mn(CO)5Br) as the catalyst.

Meyer-Schuster-type rearrangement for the synthesis of α-selanyl-α,β-unsaturated thioesters.

A new approach to prepare α-selanyl-α,β-unsaturated thioesters from propargylthioalkynes and an electrophilic selenium species is reported. Pivotal is the intermediacy of a sulfur-stabilized vinyl cation, which is captured intramolecularly and ultimately enables 37 examples of the target compounds to be prepared in good yields. Computational studies shed light on the nature of intermediates in this transformation.

Chiral Cobalt(II) Complex Catalyzed Asymmetric [2,3]-Sigmatropic Rearrangement of Allylic Selenides with α-Diazo Pyrazoleamides

Organoselenium compounds, due to their high structural diversity, special function, and biological activities, have drawn attention in synthetic chemistry. Herein, a novel example of chiral N,N′-di...

Selenocystine Peptides Performance in 5‐endo‐dig Reactions

Herein, we present methods for the generation of selenocysteinyl electrophile by weak Lewis acids or oxidants. The electrophilic selenium species were further utilized in 5‐endo‐dig cyclization reactions with 2‐ethynyl phenols, anisoles, and anilines, yielding substituted benzo[b]furans and indoles bearing short selenocysteine‐containing peptides. Copper(II) bromide promoted 5‐endo‐dig cyclization can be successfully applied for protected and unprotected peptides in high yields. Elaborated protocol allows the construction of phenylindeno[1,2‐c]chromene moiety in 5‐endo‐dig/6‐endo‐dig cascade reactions.

Arylseleninic acid as a green, bench-stable selenylating agent: synthesis of selanylanilines and 3-selanylindoles.

Arylseleninic acids were used as an electrophilic selenium source in aromatic substitution reactions, using N,N-substituted anilines and indoles as nucleophiles at 70 °C for 6-15 h. A total of fourteen 4-selanylanilines and five 3-selanylindoles were selectively obtained in good to excellent yields. The starting benzeneseleninic acids are easily prepared from the respective diselenides, are bench stable and easy to handle, affording water as the only waste at the end of the reaction.

Synthesis of 3-selanylbenzo[b]furans promoted by SelectFluor®.

A simple and practical protocol for the synthesis of 3-selanyl-benzo[b]furans mediated by the SelectFluor® reagent was developed. This novel methodology provided a greener alternative to generate 3-substituted-benzo[b]furans via a metal-free procedure under mild conditions. The intramolecular cyclization reaction was carried out employing an electrophilic selenium species generated in situ through the reaction between SelectFluor® and organic diselenides. The formation of this electrophilic selenium species (RSe-F) was confirmed by heteronuclear NMR spectroscopy, and its reactivity was explored.

Three-Component Aminoselenation of Arynes.

The three-component coupling of tertiary amines, arynes, and aryl selenium bromide or diaryl diselenide as an electrophilic selenium source allowing the synthesis of 2-selanyl aniline derivatives is reported. This aminoselenation reaction of arynes installs a C-N and C-Se bond under mild conditions, and the products are formed in moderate to good yields. This reaction is compatible with various functional groups, and the preliminary studies on the mechanism of the reaction is also provided.