Synthesis of Selenium Derivatives using Organic Selenocyanates as Masked Selenols: Chemical Reduction with Rongalite as a Simpler Tool to give Nucleophilic Selenides.

The chemical reduction within a family of organic selenocyanates, as masked selenols, using reducing agents, such as Rongalite, sodium dithionite, and sodium thiosulfate is investigated. Using Rongalite, the corresponding diselenides were obtained quantitatively and selectively in very good to excellent yields (51-100%) starting from alkyl, aryl, and benzyl selenocyanates. The scope of the reaction is unaffected by the electronic nature of the substituents. Furthermore, the reducing agent, Rongalite, is compatible with hydrolysable and reducing-sensitive functional groups. Additionally, a simple methodology employing the in-situ generated benzyl selenolate anion (PhCH2Se‾) to promote aliphatic nucleophilic substitution, epoxide ring opening, and Michael addition reactions has been developed; thus extending the structural diversity of the synthesized selenium derivatives.

Metal- and base-free, aerobic photoredox catalysis with riboflavin to synthesize 2-substituted benzothiazoles.

Sustainable approaches for the synthesis of 2-substituted benzothiazoles are sought after for their use in organic chemistry, bioorganic chemistry, and industrial applications. Here, we described a visible light-driven photoredox catalytic cyclization of thioanilides to afford 2-substituted benzothiazoles using riboflavin as a photocatalyst, where oxygen is used as a clean oxidant and ethanol as a greener solvent. These results provide a new photochemical route for environmentally benign synthesis.

Riboflavin and Eosin Y Supported on Chromatographic Silica Gel as Heterogeneous Photocatalysts.

The application of photocatalysis for organic synthesis, both in the laboratory and on an industrial scale, will depend on the achieving of good yields and the ease with which it can be applied. Selective irradiation of the photocatalyst with LED light has made it possible to activate the reactions easily, without the need for UV or heat filters. However, a common problem is the need to separate the photocatalyst from the reaction products through extraction and chromatography isolation processes. These procedures make it difficult to recover and reuse the catalyst, which is not compatible with scale-up applications. Photocatalysts attached to heterogeneous supports resulted in an alternative, which facilitates their removal and reuse. In this study, we use chromatographic silica gel as a low-cost heterogeneous support to bind photosensitizers such as Riboflavin or Eosin Y. The modified silica gel was analyzed by FTIR-ATR and diffuse reflectance UV-visible spectroscopy, thermogravimetric analysis, and optical microscopy. These hybrid materials have a suitable size for easy separation by decantation and were found to be photoactive against two photooxidation reactions. These easy-to-handle materials open the door to effective applications for photoinduced organic synthesis methods at medium to large scale.

Linker-Assisted CdS-TiO2 Nanohybrids as Reusable Visible Light Photocatalysts for the Oxidative Hydroxylation of Arylboronic Acids.

A variety of phenols have been obtained in aqueous media with moderate to excellent chemical yields (≤100%) by using arylboronic acids and esters as substrates, a robust CdS-TiO2 nanohybrid as a heterogeneous photocatalyst, visible light irradiation (467 nm), and an O2-saturated atmosphere. The nanohybrid was prepared through a linker-assisted methodology that uses mercapto alkanoic acids as the organic linkers. The nanohybrid showed improved photocatalytic activity in the hydroxylation of substituted arylboronic acids and phenyl boronic esters compared with that of pristine CdS quantum dots. The nanohybrid can be reused in up to five photocatalytic cycles with ∼90% of its outstanding activity preserved.

Photochemical Csp2-H bond thiocyanation and selenocyanation of activated arenes, batch and continuous-flow approaches.

Herein, we report an eco-friendly photochemical oxidative Csp2-H thiocyanation and selenocyanation of activated arenes. The reaction proceeds under Violet LED irradiation in the presence of K2S2O8, which quickly oxidizes KSCN and KSeCN, finally producing arylthio/selenocyanates. Using this benign, atom-economic protocol, the desired chalcogenide products were obtained regioselectively, with isolated yields that range from very good to excellent. Although, mechanistic study indicates that it is difficult to distinguish between a radical to a SEAr reaction mechanism between the photo-induced formed •SCN, for the former, or NCSSCN, for the latter, to the aromatic heterocycles. The inhibition experiment together with the observed reactivity and regioselectivity, would be in agreement with the latter. The synthetic methodology designed could be successfully adapted to continuous-flow systems in a segmented-flow regime, employing the organic phase as the product reservoir. Using this setup, the advantage of the latter can be demonstrated by reducing the reaction time and improving the product yields. Similarly, the scaling up of the reaction to gram scale resulted in favorable outcomes by the flow setup, which installs the photo-flow chemistry as a powerful tool to be included into routine reaction procedures, which have great relevance for the pharmaceutical industry.

Mechanistic Insight into the Light-Triggered CuAAC Reaction: Does Any of the Photocatalyst Go?

The attainment of transition-metal catalysis and photoredox catalysis has represented a great challenge over the last years. Herein, we have been able to merge both catalytic processes into what we have called "the light-triggered CuAAC reaction". Particularly, the CuAAC reaction reveals opposite outcomes depending on the nature of the photocatalyst (eosin Y disodium salt and riboflavin tetraacetate) and additives (DABCO, Et3N, and NaN3) employed. To get a better insight into the operating processes, steady-state, time-resolved emission, and laser flash photolysis experiments have been performed to determine reactivity and kinetic data. These results, in agreement with thermodynamic estimations based on reported data, support the proposed mechanisms. While for eosin Y (EY), Cu(II) was reduced by its triplet excited state; for riboflavin tetraacetate (RFTA), mainly triplet excited RFTA state photoreductions by electron donors as additives are mandatory, affording RFTA•- (from DABCO and NaN3) or RFTAH• (from Et3N). Subsequently, these species are responsible for the reduction of Cu(II). For both photocatalysts, photogenerated Cu(I) finally renders 1,2,3-triazole as the final product. The determined kinetic rate constants allowed postulating plausible mechanisms in both cases, bringing to light the importance of kinetic studies to achieve a strong understanding of photoredox processes.

Heterogeneous photocatalysis of azides: extending nitrene photochemistry to longer wavelengths.

The photodecomposition of azides to generate nitrenes usually requires wavelengths in the <300 nm region. In this study, we show that this reaction can be readily performed in the UVA region (368 nm) when catalyzed by Pd-decorated TiO2. In aqueous medium the reaction leads to amines, with water acting as the H source; however, in non-protic and non-nucleophilic media, such as acetonitrile, nitrenes recombine to yield azo compounds, while azirine-mediated trapping occurs in the presence of nucleophiles. The heterogeneous process facilitates catalyst separation while showing great chemoselectivity and high yields.

Riboflavin as Photoredox Catalyst in the Cyclization of Thiobenzanilides: Synthesis of 2-Substituted Benzothiazoles.

Benzothiazoles are synthesized from thiobenzanilides using riboflavin as a photosensitizer and potassium peroxydisulfate as a sacrificial oxidizing agent under visible light irradiation. The methodology accepts a broad range of functional groups and affords the 2-substituted benzothiazoles by transition-metal-free organic photoredox catalysis under very mild conditions.

Combined Experimental and Theoretical Studies on the Radical Nucleophile Addition Reaction for Sulfide- and Selenide-Centered Anions.

The reactivity of sulfur- and selenium-centered nucleophiles toward 1-naphthyl radicals was studied in dimethylsulfoxide. The photostimulated reaction of sulfide anions, -SC(NH)C6H5 (1), -SC(NH)NH2 (2), and -SC(NH)CH3 (3), renders, after the addition of MeI, methyl 1-naphthylsulfide as a main product together with bis(1-naphthyl) sulfide and naphthalene under irradiation. Concordantly, the reaction of selenide anions, -SeC(NH)C6H5 (4), -SeC(NH)NH2 (5), and -SeCN (6), produces methyl 1-naphthyl selenide, bis(1-naphthyl) selenide, and naphthalene in the presence of potassium tert-butoxide anion (entrainment conditions). Absolute rate constants for the coupling of ions 1-6 to 1-naphthyl radicals were determined; as a general trend, the selenide-centered nucleophiles enhance in 2 times the reactivity of their sulfide analogues. From the mechanistic study, it is proposed that the unstable radical anion produced by the addition of the nucleophile to 1-naphthyl radical affords, after fragmentation, 1-naphthylsulfide/selenide anion. In addition, experimental results are discussed in terms of density functional theory calculations. There is a generally good agreement between the experimental and the calculated reactivities, the spin density being the main parameter to describe the difference found among the anions under study. Moreover, the calculations predict that anion -SeC(NH)CH3 (7) would be a good candidate for the synthesis of selenide derivatives.

Regioselective Photocycloaddition of Saccharin Anion to π-Systems: Continuous-Flow Synthesis of Benzosultams.

Saccharin is a versatile scaffold to build up different heterocycles with relevance in asymmetric catalysis, agricultural chemistry, medicinal chemistry, and so forth. Here, we report a photochemical strategy to obtain seven-membered ring benzosultams in one step, using saccharin anion as starting material. The reaction can be improved in a photoflow reactor and its scope was evaluated. Furthermore, computational study at the CASPT2//CASSCF level of theory was also performed to rationalize the involved mechanism.

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.

Photoinduced One-Electron Oxidation of Aromatic Selenides: Effect of the Structure on the Reversible Dimerization Reaction.

The photochemical one-electron oxidation of alkyl aryl selenides was studied by means of laser flash photolysis (355 nm). Quenching of the sensitizers in their excited state leads to selenide radical cation in the presence of selenium derivatives. The π-type dimer of methyl phenyl selenide radical cation was detected at 630 nm at expenses of the monomeric radical cation (530 nm). The effect of modification of the aryl and alkyl substituents was also studied, resulting that the formation of dimers depends on both, the electronic properties and steric hindrance of the substituents. Both effects, an increase in steric hindrance in the alkyl moiety or the presence of strongly electron donor groups in the aromatic substituent that stabilizes the radical cation, prevent the dimer formation.

Mechanistic Insight into the Cu-Catalyzed C-S Cross-Coupling of Thioacetate with Aryl Halides: A Joint Experimental-Computational Study.

The mechanism of the Ullmann-type reaction between potassium thioacetate (KSAc) and iodobenzene (PhI) catalyzed by CuI associated with 1,10-phenanthroline (phen) as a ligand was explored experimentally and computationally. The study on C-S bond formation was investigated by UV-visible spectrophotometry, cyclic voltammetry, mass spectrometry, and products assessment from radical probes. The results indicate that under experimental conditions the catalytically active species is [Cu(phen)(SAc)] regardless of the copper source. An examination of the aryl halide activation mechanism using radical probes was undertaken. No evidence of the presence of radical species was found during the reaction process, which is consistent with an oxidative addition cross-coupling pathway. The different reaction pathways leading to the experimentally observed reaction products were studied by DFT calculation. The oxidative addition-reductive elimination mechanism via an unstable CuIII intermediate is energetically more feasible than other possible mechanisms such as single electron transfer, halogen atom transfer, and σ-bond methatesis.

Exploring the Photophysical and Photochemical Properties of N-(Thioalkyl)-saccharins as an Alternative Route to the Synthesis of Tricyclic Sultams.

Photocyclization of N-(thioalkyl)-saccharin was carried out to obtain different polycyclic sultams in good yields. These photoreactions were efficient under inert atmosphere and acetone triplet-sensitized conditions indicating that the triplet excited state is directly involved in the formation of annulated products. The presence of molecular oxygen changes product distribution, and only photo-oxygenation products (sulfoxides and sulfones) were found. This result is especially valuable since, by simple changing from nitrogen- to oxygen-saturated solvent conditions, the reaction outcome can be tuned from cyclized to sulfur oxidation products. Additionally, steady-state photolysis, electrochemistry, and laser time-resolved spectroscopic studies confirmed that these reactions mainly proceeded by intramolecular electron transfer (ET) between the triplet excited saccharin moiety and sulfur atom.

Photoremoval of protecting groups: mechanistic aspects of 1,3-dithiane conversion to a carbonyl group.

Photodeprotection of 1,3-dithianes in the presence of thiapyrylium was performed to return to the parent carbonyl compound, and the mechanism was studied by steady state photolysis, laser flash photolysis, and theoretical calculations. Electron transfer from dithianes to triplet sensitizers is extremely fast, and the decay of dithiane radical cations was not affected by the presence of water or oxygen as the consequence of a favorable unimolecular fragmentation pathway. Similar behaviors were observed for dithianes bearing electron-releasing or electron-withdrawing substituents on the aryl moiety, evidenced by C-S bond cleavage to form a distonic radical cation species. The lack of reaction under nitrogen atmosphere, requirement of oxygen for good conversion yields, inhibition of the photodeprotection process by the presence of p-benzoquinone, and absence of a labeled carbonyl final product when the reaction is performed in the presence of H2(18)O all suggest that the superoxide anion drives the deprotection reaction. Density functional theory computational studies on the reactions with water, molecular oxygen, and the superoxide radical anion support the experimental findings.

Photochemistry of N-(selenoalkyl)-phthalimides. Formation of N, Se-heterocyclic systems.

A variety of N-(selenomethyl)alkyl-phthalimides (alkyl = -(CH2)n-; n = 2-5, 1a, b, d, e) and N-(selenobenzyl)propyl phthalimide (1c) were synthesized and their photochemistry was studied at λ = 300 nm. Steady-state photolysis and laser time-resolved spectroscopy studies confirmed that these reactions proceeded by direct or acetone-sensitized excitation followed by intramolecular electron transfer (ET) between Se atom and the phthalimide moiety. Two main pathways are possible after ET: proton transfer to the ketyl radical anion from the CH3Se(+)˙ or the -CH2Se(+)˙- moieties, yielding the corresponding biradicals. Collapse of these biradicals yields cyclization products with the respective endo or exo selenium-containing heterocycles. Competition between both proton transfer processes depends on the chain length of the alkyl spacer between the phthalimide and Se groups as well as the size of the cycle being formed.

Stereoselective one-pot synthesis of ß-alkylsulfide enol esters. Base-triggered rearrangement under mild conditions.

A stereoselective one-pot procedure was developed to prepare S-substituted (Z)-enol esters through a base-triggered rearrangement. This transition metal-free multicomponent approach can be performed under an air atmosphere at room temperature, tolerates a wide set of chemical functionalities and generally affords high isolated yields. The (Z)-selectivity arises from the [1,4]-S- to O-acyl migration.