Barsegyan, Yana Arturovna

Vil’ V.A., Barsegyan Y.A., Chabuka B.K., Ilovaisky A.I., Alabugin I.V., Terent’ev A.O.

Barsegyan Y.A., Vil’ V.A., Terent’ev A.O.

Macrocycles bridge the gap between conventional small molecules and polymers. Drawing inspiration from successful carbon heteroatom-containing macrocycles, peroxide-containing macrocycles are gaining attention for enhanced bioactivity, potential chelating properties, and applications in energetic materials. This review presents the following strategies for the construction of cyclic peroxides with 10- to 36-membered frameworks: (1) the intramolecular iodocyclization of hydroperoxides, (2) the intermolecular cyclization of hydroperoxides with alkyl dihalides or carbonyls, (3) the acid-catalyzed rearrangements of ozonides or 11-membered cyclic triperoxides via oxy- or peroxycarbenium ions, and (4) the peroxidation of carbonyls targeting macrocyclic peroxides. The specific agents that allow for the selective construction of the medium and large cycles are also analyzed.

Radulov P.S., Mikhaylov A.A., Medvedev A.G., Barsegyan Y., Belyaev E., Dmitrieva V.E., Tripol'skaya T.A., Mel`nik E., Vil' V.A., Yaremenko I.A., Prikhodchenko P.V., Terent'ev A.O.

This study reports a convenient, safe and recyclable source of anhydrous H2O2 for organic peroxide synthesis. It is based on the generation of H2O2 through the reaction of ZnO2 with H2SO4 and the recycling of ZnO2 from ZnSO4 and 1 wt% H2O2.

Vil’ V.A., Barsegyan Y.A., Kuhn L., Terent’ev A.O., Alabugin I.V.

Kuhn L., Vil’ V.A., Barsegyan Y.A., Terent’ev A.O., Alabugin I.V.

We show that the carboxylate radical acts as an L-ligand with certain high-spin transition metal centers. Such coordination preserves the O-radical character needed for C-H activation via hydrogen atom transfer. Capture of the new C-radical by the metal and subsequent reductive elimination leads to formal C-H acyloxylation. Decarboxylation of the RCO2 radical is minimized through hybridization effects introduced by spiro-cyclopropyl moiety.

Barsegyan Y., Vil’ V.A., Tomkinson N.C., Terent'ev A.O.

AbstractThis chapter describes methods for the preparation of cyclic diacyl peroxides and their application as reagents in organic synthesis. Reaction of these peroxides with C=C and C-H compounds results in the selective formation of new C-O bonds.

Vedenyapina M.D., Skundin A.M., Vil’ V.A., Kazakova M.M., Barsegyan Y.A.

The anodic behavior of gold in solutions containing spirocyclopentyl malonyl peroxide is studied via cyclic voltammetry. It is found that gold dissolves under anodic polarization with the formation of a complex of singly charged cations with spirocyclopentyl malonyl peroxide as a ligand. Gold in this case corrodes at lower potentials (about 500 mV) than in the supporting solution.

Baranov V.V., Barsegyan Y.A., Strelenko Y.A., Karnoukhova V.A., Kravchenko A.N.

New aspects of multicomponent condensation reactions of ethylene/propylenediamine, formaldehyde and unsubstituted and 1-methyl substituted semithio- and dithioglycolurils have been examined. Ethylene-linked 2,3a,4a,6,9,10a,11aheptaaza-6,9-methanobenzo[cd]cyclonona[gh]pentalene and 2,6:10,14-dimethano-2,6,7a,8a,10,14,15a,16a-octaazadicyclodeca[cd,gh]pentalene as well as their simpler analogues were synthesized, and their structures were proved by 1D and 2D NMR spectroscopy, HRMS and X-ray analysis.

Vil' V.A., Barsegyan Y.A., Kuhn L., Ekimova M.V., Semenov E.A., Korlyukov A.A., Terent'ev A.O., Alabugin I.V.

How far can we push the limits in removing stereoelectronic protection from an unstable intermediate? We address this question by exploring the interplay between the primary and secondary stereoelectronic effects in the Baeyer–Villiger (BV) rearrangement by experimental and computational studies of γ-OR-substituted γ-peroxylactones, the previously elusive non-strained Criegee intermediates (CI). These new cyclic peroxides were synthesized by the peroxidation of γ-ketoesters followed by in situ cyclization using a BF3·Et2O/H2O2 system. Although the primary effect (alignment of the migrating C–Rm bond with the breaking O–O bond) is active in the 6-membered ring, weakening of the secondary effect (donation from the OR lone pair to the breaking C–Rm bond) provides sufficient kinetic stabilization to allow the formation and isolation of stable γ-hydroperoxy-γ-peroxylactones with a methyl-substituent in the C6-position. Furthermore, supplementary protection is also provided by reactant stabilization originating from two new stereoelectronic factors, both identified and quantified for the first time in the present work. First, an unexpected boat preference in the γ-hydroperoxy-γ-peroxylactones weakens the primary stereoelectronic effects and introduces a ∼2 kcal mol−1 Curtin–Hammett penalty for reacquiring the more reactive chair conformation. Second, activation of the secondary stereoelectronic effect in the TS comes with a ∼2–3 kcal mol−1 penalty for giving up the exo-anomeric stabilization in the 6-membered Criegee intermediate. Together, the three new stereoelectronic factors (inverse α-effect, misalignment of reacting bonds in the boat conformation, and the exo-anomeric effect) illustrate the richness of stereoelectronic patterns in peroxide chemistry and provide experimentally significant kinetic stabilization to this new class of bisperoxides. Furthermore, mild reduction of γ-hydroperoxy-γ-peroxylactone with Ph3P produced an isolable γ-hydroxy-γ-peroxylactone, the first example of a structurally unencumbered CI where neither the primary nor the secondary stereoelectronic effect are impeded. Although this compound is relatively unstable, it does not undergo the BV reaction and instead follows a new mode of reactivity for the CI – a ring-opening process.

Vedenyapina M.D., Skundin A.M., Vil’ V.A., Kazakova M.M., Barsegyan Y.A.

The electrochemical reduction of spirocyclopentylmalonyl peroxide in an aqueous medium is studied via cyclic voltammetry on a gold stationary electrode. Based on calculations using parameters of cyclic voltammetry recorded at different scan rates, it is concluded that the studied material underwent two successive one-electron reductions, and a scheme is proposed for its cathodic reduction.

Barsegyan Y.A., Vil’ V.A.

A summary of the most recent applications of malonyl peroxides as reagents in organic synthesis is discussed. The microreview covers the latest selected examples on the usage of malonyl peroxides: dioxygenation and oxyamination of alkenes; oxidative C–O coupling with arenes, enol ethers, 1,3-dicarbonyl and N-heterocyclic compounds; sulfoxide synthesis.

Vil' V.A., Barsegyan Y.A., Barsukov D.V., Korlyukov A.A., Alabugin I.V., Terent'ev A.O.

Stereoelectronic interactions control reactivity of peroxycarbenium cations, the key intermediates in (per)oxidation chemistry. Computational analysis suggests that alcohol involvement as a third component in the carbonyl/peroxide reactions remained invisible due to the absence of sufficiently deep kinetic traps needed to prevent the escape of mixed alcohol/peroxide products to the more stable bisperoxides. Synthesis of β-alkoxy-β-peroxylactones, a new type of organic peroxides, was accomplished by interrupting a thermodynamically driven peroxidation cascade. The higher energy β-alkoxy-β-peroxylactones do not transform into the more stable bisperoxides due to the stereoelectronically-imposed instability of a cyclic peroxycarbenium intermediate as a consequence of amplified inverse alpha-effect. The practical consequence of this fundamental finding is the first three-component cyclization/condensation of β-ketoesters, H 2 O 2 , and alcohols that provides β-alkoxy-β-peroxylactones in 15-80% yields.

Vil' V.A., Gorlov E.S., Bityukov O.V., Barsegyan Y.A., Romanova Y.E., Merkulova V.M., Terent'ev A.O.

AbstractMalonyl peroxides act both as oxidants and reagents for C−O coupling in reactions with methyl and silyl enol ethers. In the proposed conditions, the oxidative C−O coupling of malonyl peroxides with enol ethers selectively proceeds, bypassing the traditional Rubottom hydroxylation of enol ethers by peroxides. It was observed that the oxidative [5+2] cycloaddition of malonyl peroxides and enol ethers is the key stage of the discovered process. Oxidative C−O coupling of silyl enol ethers leads to the formation of α‐acyloxyketones with a free carboxylic acid group. A specially developed preparative one‐pot procedure transforms ketones via silyl enol ethers formation and the following coupling into α‐acyloxyketones with yields 35–88%. The acid‐catalyzed coupling with methyl enol ethers gives remarkable products while retaining the easily oxidizable enol fragment. Furthermore, these molecules contain a free carboxylic acid group, thus these nontrivial products contain two usually incompatible acid and enol ether groups.magnified image

Baranov V.V., Barsegyan Y.A., Kolotyrkina N.G., Kravchenko A.N.

A highly selective one-pot synthesis of new 6-substituted 4-thioxohexahydro-5H-2,3,4a,6,7a-pentaazacyclopenta[cd]inden-1(2H)-ones by cycloaminomethylation of semithioglycolurile with formaldehyde and amines is proposed. A mechanism for the process is suggested.

Barsegyan Y., Baranov V., Kravchenko A., Strelenko Y., Anikina L., Karnoukhova V., Kolotyrkina N.

A two-step one-pot condensation for the synthesis of previously inaccessible 2,6-disubstituted 2,3a,4a,6,7a,8a-hexaazaperhydrocyclopenta[def]fluorene-4-thioxo-8-ones from simple reagents [5-thioxohexahydroimidazo[4,5-d]imidazol-2(1H)-one, paraformaldehyde and amines] was developed. The structure, antimicrobial, and anticancer activity of a number of synthesized compounds were studied.

Vil’ V.A., Barsegyan Y.A., Chabuka B.K., Ilovaisky A.I., Alabugin I.V., Terent’ev A.O.

Gavrilov G.A., Nguyen T.K., Katkova S.A., Rostovskii N.V., Rogacheva E.V., Kraeva L.A., Kinzhalov M.A.

AbstractA novel and concise approach to rare 2,3,5‐triamino‐imidazole scaffolds via Ni‐catalyzed coupling of alkylisocyanides and N,N′‐diarylguanidines has been developed. This reaction features include mild conditions (thermal or visible light activation), a wide substrate scope, and high efficiency. The coupling proceeds through a NiII/NiIV catalytic cycle, involving two‐electron aerobic oxidation and the sequential insertion of two isocyanide units into Ni−N bonds.Testing these compounds against pathogens of the ESKAPE panel showed their high activity with a minimum inhibitory concentration down to 0.38 μg/mL.

Yuan H., Wang L., Li S., Zhu Z., Yao J., Li H., Li Y., Qu J.

Chandrasekhar S.

Stoykov I.I., Antipin I.S., Burilov V.A., Kurbangalieva A.R., Rostovsky N.V., Pankova A.S., Balova I.A., Remizov Y.O., Pevzner L.M., Petrov M.L., Vasily A.V., Averin A.D., Beletskaya I.P., Nenaydenko V.G., Beloglazkina E.K., et. al.

An overview of the main scientific achievements of Russian universities in the field of organic chemistry for the period 2018–2023 is presented.

Belyakova Y.Y., Radulov P.S., Novikov R.A., Prolomov I.V., Krivoshchapov N.V., Medvedev M.G., Yaremenko I.A., Alabugin I.V., Terent’ev A.O.

Polyakov M.V., Vedenyapina M.D., Skundin A.M., Yaremenko I.A., Radulov P.S.

Cyclic voltammetry and gravimetry are used to study the behavior of a smooth gold electrode in a medium of bridged 1,2,4-trioxalane in acetonitrile. It is found that the peroxide bond in the molecule of bridged 1,2,4-trioxalane is reduced on the surface of the electrode during the cathodic process, with the subsequent formation of a diketone fragment. The formation of colloidal gold particles is detected during anodic oxidation.

Mikhaylov A.A., Medvedev A.G., Egorov P.A., Mayorov N.S., Zhizhin K.Y., Prikhodchenko P.V.

Hydrogen peroxide is a valuable reagent that is produced on an industrial scale. However, the concentration of commercially available H2O2 does not exceed 70 wt % and usually contains stabilizers that prevent the decomposition of aqueous solutions of H2O2 during storage and transportation. At the same time, there are processes and reactions that require small quantities of pure, anhydrous hydrogen peroxide. This paper describes a two-stage method for producing anhydrous hydrogen peroxide in the laboratory. Distillation of an aqueous solution of hydrogen peroxide in the first stage allows to obtain pure diluted H2O2. Subsequent distillation of water under vacuum allows to obtain highly concentrated or anhydrous H2O2 in quantities sufficient for laboratory use. This approach is safe only if certain rules are strictly followed when working with concentrated hydrogen peroxide.

Radulov P., Skokova K., Dmitrieva V., Fomenkov D., Krylov I., Ilovaisky A., Yaremenko I., Terent'ev A.

AbstractA three‐component reaction of 1,3‐diketones with H2O2 and alcohols was discovered. 3,5‐Dialkoxy‐1,2‐dioxolanes are formed in yields ranging from 13% to 83% using an excess of acids such as H2SO4, MeHSO3, p‐TsOH⋅H2O or BF3⋅Et2O. This reaction proceeds with the formation of 3,5‐dialkoxy‐1,2‐dioxolanes despite the diversity of possible reaction pathways leading to different types of peroxides, oligomers, polymers or hydrolysis. 3,5‐Dimethoxy‐1,2‐dioxolanes exhibit high activity against phytopathogenic fungi.

Barsegyan Y.A., Vil’ V.A., Terent’ev A.O.

Macrocycles bridge the gap between conventional small molecules and polymers. Drawing inspiration from successful carbon heteroatom-containing macrocycles, peroxide-containing macrocycles are gaining attention for enhanced bioactivity, potential chelating properties, and applications in energetic materials. This review presents the following strategies for the construction of cyclic peroxides with 10- to 36-membered frameworks: (1) the intramolecular iodocyclization of hydroperoxides, (2) the intermolecular cyclization of hydroperoxides with alkyl dihalides or carbonyls, (3) the acid-catalyzed rearrangements of ozonides or 11-membered cyclic triperoxides via oxy- or peroxycarbenium ions, and (4) the peroxidation of carbonyls targeting macrocyclic peroxides. The specific agents that allow for the selective construction of the medium and large cycles are also analyzed.

Kim N., Choi M., Suh S., Chenoweth D.M.

Samulionis A.S., Medvedev A.G., Tripol’skaya T.A., Kiskin M.A., Prikhodchenko P.V., Eremenko I.L., Nikolaevskii S.A.

The interaction of the binuclear complex [Zn2(Рiv)4(Рhen)2] with water in toluene or acetonitrile results in its monomerization with the formation of compound [Zn(Рiv)2(H2O)(Рhen)], the crystal structure of which is determined by XRD (CIF file CСDC no. 2374361). The individual character of the formed crystalline phase is confirmed by powder XRD. Nanoparticles of zinc peroxide/hydroxide are proposed to be used as a water source for the obtaining of single crystals of [Zn(Рiv)2(H2O)(Рhen)] suitable for XRD.

Zaikina L.A., Mulina O.M., Merkulova V.M., Ilovaisky A.I., Vil’ V.A., Terent'ev A.O.

Abstractβ‐Ketosulfones were synthesized from enol acetates and sodium sulfinates under electrochemical conditions. The starting sulfinates can act both as the supporting electrolyte and as the source of S‐centered radicals, allowing electrolysis to proceed without external salt. Side reactions of enol acetates’ oxidation are not observed, and the developed process is quite selective. The proposed electrochemical sulfonylation is compatible with a wide range of the initial enol acetates and sulfinates. On the basis of literature data, control experiments, and CV studies, the presumable reaction pathway is suggested. The key intermediates are S‐centered sulfonyl radical, C‐centered benzylic radical, and β‐acetoxy‐β‐hydroxysulfone.

Xie K.A., Bednarova E., Joe C.L., Sherwood T.C., Welin E.R., Rovis T.

Mukherjee S., Aoki Y., Kawamura S., Sodeoka M.

AbstractPolyhalogenated molecules are often found as bioactive compounds in nature and are used as synthetic building blocks. Fluoroalkyl compounds hold promise for the development of novel pharmaceuticals and agrochemicals, as the introduction of fluoroalkyl groups is known to improve lipophilicity, membrane permeability, and metabolic stability. Three‐component 1,2‐halo‐halodifluoromethylation reactions of alkenes are useful for their synthesis. However, general methods enabling the introduction of halodifluoromethyl (CF2X) and halogen (X’) groups in the desired combination of X and X’ are lacking. To address this gap, for the first time, we report a three‐component halo‐halodifluoromethylation of alkenes and alkynes using combinations of commercially available fluorinated carboxylic anhydrides ((CF2XCO)2O, X=Cl and Br) and alkali metal halides (X’=Cl and Br). In situ prepared fluorinated diacyl peroxides were identified as important intermediates, and the use of appropriate bipyridyl‐based ligands and a copper catalyst was essential for achieving high product selectivity. The synthetic utility of the polyhalogenated products was demonstrated by exploiting differences in the reactivities of their C−X and C−X’ bonds to achieve selective derivatization. Finally, the reaction mechanism and ligand effect were investigated using experimental and theoretical methods to provide important insights for the further development of catalytic reactions.

Belyakova Y.Y., Radulov P.S., Novikov R.A., Prolomov I.V., Krivoshchapov N.V., Medvedev M.G., Yaremenko I.A., Alabugin I.V., Terent’ev A.O.

Bityukov O.V., Serdyuchenko P.Y., Kirillov A.S., Nikishin G.I., Vil’ V.A., Terent’ev A.O.

Organic peroxides have become sought-after functionalities, particularly following the multi-tone consumption in polymer production and success in medicinal chemistry. The selective introduction of a peroxide fragment at different positions on the target molecule is a priority in the modern reaction design. The pioneering Kharasch–Sosnovsky peroxidation became the basic universal platform for the development of peroxidation methods, with its great potential for rapid generation of complexity due to the ability to couple the resulting free radicals with a wide range of partners. This review discusses the recent advances in the radical Kharasch-type functionalization of organic molecules with OOR fragment including free-component radical couplings. The discussion has been structured by the type of the substrate of radical peroxidation: C(sp3)–H substrates; aromatic systems; compounds with unsaturated C–C or C–Het bonds.

Fu K., Shi L.

Barsegyan Y.A., Vil’ V.A., Terent’ev A.O.

Macrocycles bridge the gap between conventional small molecules and polymers. Drawing inspiration from successful carbon heteroatom-containing macrocycles, peroxide-containing macrocycles are gaining attention for enhanced bioactivity, potential chelating properties, and applications in energetic materials. This review presents the following strategies for the construction of cyclic peroxides with 10- to 36-membered frameworks: (1) the intramolecular iodocyclization of hydroperoxides, (2) the intermolecular cyclization of hydroperoxides with alkyl dihalides or carbonyls, (3) the acid-catalyzed rearrangements of ozonides or 11-membered cyclic triperoxides via oxy- or peroxycarbenium ions, and (4) the peroxidation of carbonyls targeting macrocyclic peroxides. The specific agents that allow for the selective construction of the medium and large cycles are also analyzed.

Yuan T., Fu K., Shi L.

Herein, we have developed an efficient PdII-catalyzed intramolecular oxidative C–H amination under additive-free and green conditions where strained cyclic diacyl peroxide functions as both a sacrificial oxidant and a bidentate linker.

Yaremenko I.A., Fomenkov D.I., Budekhin R.A., Radulov P.S., Medvedev M.G., Krivoshchapov N.V., He L., Alabugin I.V., Terent’ev A.O.

Bityukov O.V., Skokova K.V., Vil’ V.A., Nikishin G.I., Terent’ev A.O.

He Z., Moreno J.A., Swain M., Wu J., Kwon O.

Great efforts have been directed toward alkene π bond amination. In contrast, analogous functionalization of the adjacent C(sp 3 )–C(sp 2 ) σ bonds is much rarer. Here we report how ozonolysis and copper catalysis under mild reaction conditions enable alkene C(sp 3 )–C(sp 2 ) σ bond–rupturing cross-coupling reactions for the construction of new C(sp 3 )–N bonds. We have used this unconventional transformation for late-stage modification of hormones, pharmaceutical reagents, peptides, and nucleosides. Furthermore, we have coupled abundantly available terpenes and terpenoids with nitrogen nucleophiles to access artificial terpenoid alkaloids and complex chiral amines. In addition, we applied a commodity chemical, α-methylstyrene, as a methylation reagent to prepare methylated nucleosides directly from canonical nucleosides in one synthetic step. Our mechanistic investigation implicates an unusual copper ion pair cooperative process.

Wang P., Chen J., Xiao W.

Kawamura S., Sodeoka M.

AbstractThe demand for practical methods for the synthesis of novel fluoroalkyl molecules is increasing owing to their diverse applications. Our group has achieved efficient difunctionalizing fluoroalkylations of alkenes using fluorinated carboxylic anhydrides as user‐friendly fluoroalkyl sources. Fluorinated diacyl peroxide, prepared in situ from carboxylic anhydrides, enables the development of novel reactions when used as a radical fluoroalkylating reagent. In this account, we aim to provide an in‐depth understanding of the structure, bonding, and reactivity of fluorinated diacyl peroxides and radicals as well as their control in fluoroalkylation reactions. In the first part of this account, the physical properties and reactivity of diacyl peroxides and fluoroalkyl radicals are described. In the subsequent part, we categorize the reactions into copper‐catalyzed and metal‐free methods utilizing the oxidizing properties of fluorinated diacyl peroxides. We also outline examples and mechanisms.

Liu H., Wu Y., Liu L., Yu J., Pan C.

A decarboxylative alkylation of enamides with alkyl diacyl peroxides induced by visible-light is described. The chemo-, regio- and stereoselective olefinic β-C–H alkylation generates a series of primary- and secondary alkylated...

Mahmudiyarova N.N., Ishmukhametova I.R., Dzhemilev U.M.

Cyclocondensation reaction of linear α,ω-diols (C3, C5, C6, and C8) with 1,1-dihydroperoxycycloalkanes and formaldehyde with the participation of lanthanide catalysts affords spiromacrocyclic diperoxides.

Shi P., Tu Y., Ma D., Bolm C.

AbstractA copper‐catalyzed N‐alkylation of NH‐sulfoximines with alkyl diacyl peroxides under blue light LED irradiation is reported. The process has a good functional group tolerance, and the products are obtained in yields ranging from 45–91%.magnified image

Alabugin I., Kuhn L.

Dworkin J.H., Dehnert B.W., Kwon O.

AbstractOrganic peroxides are becoming popular intermediates for novel chemical transformations. The weak O–O bond is readily reduced by transition metals, including iron and copper, to initiate a radical cascade process that breaks C–C bonds. Great potential exists for the rapid generation of complexity, originating from the ability to couple the resulting free radicals with a wide range of partners. First, this review article discusses the history and synthesis of organic peroxides, providing the context necessary to understand this methodology. Then, it highlights 91 examples of recent applications of the radical functionalization of C–C bonds accessed through the transition metal-mediated reduction of organic peroxides. Finally, we provide some comments about safety when working with organic peroxides.