Vera A. Vil’

• PhD Organic Chemistry
• Researcher at N.D. Zelinsky Institute of Organic Chemistry

A key goal of organic chemistry is to develop new principles for the control of reactions, which can be used to create promising materials demanded in all fields of scientific research and industry. This review is an overview of the scientific advances, which have been made by the N. D. Zelinsky Institute of Organic Chemistry of the Russian Academy...

Alkene ozonolysis is mostly known as a textbook reaction, resulting in carbonyl compounds. The combination of ozone and hydroperoxide was found to lead to the construction of more oxygen-rich compounds, unsymmetrical geminal bisperoxides, avoiding as well further oxidation with ozone, hydroperoxide, and oxygen as peroxide rearrangements. The discov...

Here, we first report the 2′-acyloxy-1,3-dicarbonyl compound construction in a three-component oxidative reaction of alkyl ketene dimer with cyclic diacyl peroxide and trimethyl orthoformate. The discovered synthesis allows us to form 2′-functionalized 1,3-dicarbonyl compounds instead of the common 2-functionalized moiety. The reaction between 4-bu...

The introduction of thiocyano groups into organic molecules is important for the preparation of many active ingredients and synthetic intermediates. A commonly used and attractive strategy is the nucleophilic substitution of halogens with the SCN anion or oxidative thiocyanation using an excess amount of external oxidants. A sustainable alternative...

Over the past decades, studies of cyclic diacyl peroxides have shown superior or even fundamentally new reactivity compared to their acyclic counterparts in various reactions. Previously, the scope of cyclic diacyl peroxides was limited to the mono peroxy compounds. The first doubled cyclic diacyl peroxide is presented herein. The diperoxide was ch...

An electrochemically induced synthesis of imidazoles from vinyl azides and benzyl amines was developed. A wide range of imidazoles were obtained, with yields of 30 to 64%. The discovered transformation is a multistep process whose main steps include the generation of electrophilic iodine species, 2H-azirine formation from the vinyl azide, followed...

The reactions of O-electrophiles, such as organic peroxides, with carbon nucleophiles are an umpolung alternative to the common approaches to C-O bond formation. Nucleophilic substitution at the oxygen atom of cyclic diacyl peroxides by enol acetates with the following deacylation leads to α-acyloxyketones with an appended carboxylic acid in 28-87%...

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 R...

The electrochemical thiocyanation of barbituric acids with NH4SCN was disclosed in an undivided cell under constant current conditions. The electrosynthesis is the most efficient at a record high current density (janode ≈50-70 mA cm-2). NH4SCN has a dual role as the source of the SCN group and as the electrolyte. Electrochemical thiocyanation of ba...

Electrochemical synthesis of cyclic ether‐annulated tetrahydroquinolines from imines and cyclic ethers in an undivided cell under constant current conditions was developed. The electrosynthesis proceeds via the enol ether formation from ethers following the aza‐Diels‐Alder [4+2] cycloaddition. The method is applicable to a wide range of imines and...

This 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.

Correction for ‘Stereoelectronic power of oxygen in control of chemical reactivity: the anomeric effect is not alone’ by Igor V. Alabugin et al. , Chem. Soc. Rev. , 2021, DOI: 10.1039/d1cs00386k.

The reactivity of CH-acidic and structurally related enol-containing heterocycles towards N-oxyl radicals was disclosed. Traditionally, these substrates were considered as reactants for ionic transformations. Highly selective and efficient N-oxyl radical mediated C–O coupling of substituted barbituric or Meldrum’s acids with N-hydroxy compounds (N-...

The chameleonic properties of oxygen accounts for the diverse reactivity of O-functionalities and their profound role in organic synthesis.

The review covers the state of the art in methods of synthesis of acyclic geminal bis-peroxides, including bis-hydroperoxides, bis(1-hydroperoxyalkyl) peroxides, and 1-hydroperoxyalkyl 1-hydroxyalkyl peroxides. Most attention has been paid to the literature since 2000. This period of time is characterized by studies of mechanisms of formation of pe...

Bromohydrins and their ethers were electrochemically synthesized via hydroxy‐ and alkoxybromination of alkenes using potassium bromide and water or alcohols. High selectivity of bromohydrins formation was achieved only with the use of DMSO as the solvent and an acid as the additive. The proposed combination of starting reagents, additives, and solv...

An acetal fragment is a well-known protective group which does not activate the neighboring α-position. Selective functionalization of non-activated acetal α-position with formal retaining of the acetal fragment was realized...

Bridged 1,2,4,5-tetraoxanes were prepared using available acidic ion exchange resin with high yields despite the possibility of peroxide decomposition under heterogeneous conditions. The bridged tetraoxanes demonstrated high cytotoxicity against HeLa cancer cells in vitro, which in some cases was higher than that of cisplatin, artesunate, and dihyd...

The TBHP-promoted selective radical addition of tetrahydrofuran to imines resulting in β-amino ethers has been developed. The presented radical method of β-amino ether synthesis is based on initiation by available TBHP and does not require metal catalysis or light irradiation. Variety of β-amino ethers are formed in good to excellent yields, despit...

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...

A summary of the most recent applications of metal-based Lewis acids (MTO, Bi(OTf)3, SnCl4, and TiCl4) as catalysts for the synthesis of cyclic organic peroxides is discussed.

A regioselective Baeyer–Villiger oxidation of estrone and androstane derivatives into 17a‐oxa‐D‐homosteroids was developed. An important feature of this reaction lies in the selective formation of oxidation products in moderate to high yields using BF3·Et2O/ H2O2 system traditionally applied for peroxide synthesis.

This chapter describes synthetic approaches to geminal noncyclic bisperoxides such as geminal bishydroperoxides, geminal bisperoxides, bis(1-hydroperoxyalkyl) peroxides, and 1-hydroperoxyalkyl 1-hydroxyalkyl peroxides. Classical approaches to the preparation of geminal bisperoxides are based on Lewis or Brønsted acid catalyzed peroxidation of carbo...

This chapter is dedicated to the interesting class of rare natural organic compounds that contain a 1,2-dioxetane ring. It is mainly concerned with the formation of such peroxides, as well as their isolation from natural sources and participation in bio-oxidation pathways.

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 synthe...

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 mixe...

The significant spread of helminth and protozoan infections, the uncontrolled intake of the known drugs by a large population, the emergence of resistant forms of pathogens have prompted people to search for alternative drugs. In this review, we have focused attention on structures and synthesis of peroxides active against parasites causing neglect...

Malonyl 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]...

Cyclobutanes containing one oxygen atom in a molecule are called oxetane-containing compounds (OCC). More than 600 different OCC are found in nature; they are produced by microorganisms, and also found in marine invertebrates and algae. The greatest number of them is found in plants belonging to the genus Taxus. Oxetanes are high-energy oxygen-cont...

Diepoxy-containing compounds are widely distributed in nature. These metabolites are found in plants and marine organisms and are also produced by many microorganisms, fungi, or fungal endophytes. Many of these metabolites are antibiotics and exhibit a wide variety of biological activities. More than 80 α,β-diepoxy-containing compounds are presente...

Cyclobutanes containing one oxygen atom in a molecule are called oxetane-containing compounds (OCC). More than 600 different OCC are found in nature; they are produced by microorganisms, and also found in marine invertebrates and algae. The greatest number of them is found in plants belonging to the genus Taxus. Oxetanes are high-energy oxygen-cont...

Malonyl peroxides were used for the one-pot construction of hybrid structures by conjugation of heterocycle (3H-pyrazol-3-one, isoxazol-5(2H)-one, pyrazolidine-3,5-dione, or barbituric acid) and amine or alcohol. The first stage represents oxidative C–O coupling with liberation of the carboxyl group which is functionalized at the second stage thus...

Hydroperoxides are a small and interesting group of biologically active natural marine compounds. All these metabolites contain a group (R-O-O-H). In this mini-review, studies of more than 80 hydroperoxides isolated from bacteria, fungi, algae, and marine invertebrates are described. Hydroperoxides from the red, brown, and green algae exhibit high...

It was discovered that the Kharasch peroxidation of barbituric acids proceeds both with a Cu-catalyst and without a metal catalyst. Despite the presence of possible thermal-initiated side oxidation pathways, α-tert-butylperoxybarbiturates were selectively prepared from substituted barbituric acids and tert-butyl hydroperoxide.

This mini review is devoted to an interesting group of natural terpenoids called highly oxygenated isoprenoid lipids (HOIL). Their producers are microorganisms, as well as they are found in plants, fungi, animals and marine organisms. The present review consists of three parts. For all three groups of HOIL presented, the chemical structure and the...

The electrochemically-induced cross-dehydrogenative С-O coupling of β-diketones and β-ketoesters (C-H reagents) with carboxylic acids (O-H reagents) was developed. An important feature of this reaction lies in the selective formation of intermolecular С-O coupling products in high yields, up to 92 %, using DMSO as a solvent with a broad substrate s...

Silica gel was found to mediate decarboxylation of tetracarbonyl compounds with a free carboxylic group prepared from β-dicarbonyl compounds and malonyl peroxides. Under solvent-free heterogeneous conditions silica gel effectively acts as a mediator of C–O coupling with further decarboxylation at 120 °C.

We have discovered synthetic access to β-hydroperoxy-β-peroxylactones via BF3-catalyzed cyclizations of a variety of acyclic precursors, β-ketoesters and their silyl enol ethers, alkyl enol ethers, enol acetates, and cyclic acetals, with H2O2. Strikingly, independent on the choice of starting material, these reactions converge at the same β-hydrope...

Peroxides represent a large and interesting group of biologically active natural compounds. All these metabolites contain a peroxide group (R-O-O-R). This review describes studies of more than 60 peroxides isolated from plants and fungi. Most of the plant peroxy steroids exhibit high antiprotozoal (Plasmodium) activity with a confidence of up to 95...

Easily available dimethylmalonoyl peroxide is proposed as a reactive alternative to the widely known spirocyclopropyl analogue for the use in the arene acyloxylation and other oxidative reactions.

Reactions of 1,5-diketones with H2O2 open an ozone-free approach to ozonides. Bridged ozonides are formed readily at the room temperature in the presence of strong Brønsted or Lewis acids such as H2SO4, p-TsOH, HBF4, or BF3•Et2O. The expected bridged tetraoxanes, the products of double H2O2 addition, were not detected. This procedure is readily sca...

The instability of hydroxyl peroxyesters, the elusive Criegee intermediates of the Baeyer-Villiger rearrangement, can be alleviated by selective deactivation of stereoelectronic effects that promote the 1,2-alkyl shift. Stable cyclic Criegee intermediates constrained within a five-membered ring can be prepared by mild reduction of respective hydrop...

The instability of hydroxy peroxyesters, the elusive Criegee intermediates of the Baeyer–Villiger rearrangement, can be alleviated by selective deactivation of the stereoelectronic effects that promote the 1,2‐alkyl shift. Stable cyclic Criegee intermediates constrained within a five‐membered ring can be prepared by mild reduction of the respective...

The biological activity of organic peroxides is usually associated with the antimalarial properties of artemisinin and its derivatives. However, the analysis of published data indicates that organic peroxides exhibit a variety of biological activity, which is still being given insufficient attention. In the present review, we deal with natural, sem...

The electrochemical behavior of phthaloyl peroxide C8H4O4 on an Au disk electrode in a 0.05 M aqueous solution of Na2SO4 was studied by cyclic voltammetry (CVA). It demonstrated a high activity in cathodic reduction with the formation of an irreversible peak on the CVA curve at E =–0.81 V. Additionally, during the anodic oxidation of C8H4O4, the su...

Organic systems still dominate several traditional areas of chemical science and well-known applications, such as the synthesis of pharmaceutical compounds and drugs. However, a fascinating trend has appeared recently to combine pure organic systems into advanced molecular architectures and to create hybrid molecular systems. These interdisciplinar...

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Oxidative functionalization of 3H-pyrazol-3-ones, isoxazol-5(2H)-ones, pyrazolidine-3,5-diones, and barbituric acids by malonyl peroxides results exclusively in C−O coupling products. Traditional hydroxylation, formation of carbonyl groups, or oxidative destruction of the heterocyclic ring are not observed. Under optimized reactions conditions – fl...

For the first time silica gel was observed to activate peroxides in oxidative coupling reactions. Here we report silica gel mediated oxidative C–O coupling of β-dicarbonyl compounds with cyclic diacyl peroxides affording α-acyloxy derivatives with 100% atom efficiency. The highest yields of coupling products were achieved in solvent free conditions...

The present review summarizes publications on the artemisinin peroxide fragment synthesis from 1983 to 2016. The data are classified according to the structures of a precursor used in the key peroxidation step of artemisinin peroxide cycle synthesis. The first part of the review comprises the construction of artemisinin peroxide fragment in total s...

The kinetics of adsorption of benzoyl peroxide from solutions in ethanol and n-hexane on coconut shell activated carbon was studied. It was found that the kinetics of adsorption of benzoyl peroxide is described by a pseudo-first-order rate equation. The adsorption isotherm of benzoyl peroxide at its equilibrium concentrations from 0.07 to 1.25 g/L...

This review is the first to collate and summarize main data on named and unnamed rearrangement reactions of peroxides. It should be noted, that in the chemistry of peroxides two types of processes are considered under the term rearrangements. These are conventional rearrangements occurring with the retention of the molecular weight and transformati...

The used peroxides act both as oxidant and reagent for the C—O coupling.

The alcoholysis of malonyl peroxides of type (I) is studied.

Corresponding author. Fax: +91-74991358824.

The lanthanide-catalyzed oxidative С-O coupling of 1,3-dicarbonyl compounds with diacyl peroxides, specifically the cyclic malonyl peroxides, has been developed. An important feature of this new reaction concerns the advantageous role of the peroxide acting both as oxidant and reagent for C-O coupling. It is shown that lanthanide salts may be used...

The unusual stability of bis- and tris-peroxides contradicts the conventional wisdom -- some of them can melt without decomposition at temperatures exceeding 100 oC. In this work, we disclose a stabilizing stereoelectronic effect that two peroxide groups can exert on each other. This stabilization originates from strong anomeric nO[rightward arrow]...

The lanthanide-catalyzed oxidative C-O coupling of α-substituted 1,3-dicarbonyl compounds with diacyl peroxides (act both as oxidant and oxygen substituent) affords oxygen-functionalized adducts in up to 94% yield. The products of this convenient and efficient transformation serve as potentially valuable precursors for the synthesis of natural prod...

The present review summarizes primary publications on the cross-dehydrogenative C–O coupling, with special emphasis on the studies published after 2000. The starting compound, which donates a carbon atom for the formation of a new C–O bond, is called the CH-reagent or the C-reagent, and the compound, an oxygen atom of which is involved in the new b...

Corresponding author. Fax: +7 499 135 8824.

Reactions of beta-diketones and beta-keto esters with tert-butyl hydroperoxide under heterogeneous conditions using SiO2-supported copper(II) perchlorate as a catalyst give rise to alpha-peroxidation products in 65-82% yields. A possibility to reuse the catalyst was demonstrated.

The reaction of β,δ-triketones with an ethereal solution of H2O2 catalyzed by heteropoly acids in the presence of a polar aprotic co-solvent proceeds via three pathways to form three classes of peroxides: tricyclic monoperoxides, bridged tetraoxanes, and a pair of stereoisomeric ozonides. The reaction is unusual in that produces bridged tetraoxanes...

The present review describes the current status of synthetic five and six-membered cyclic peroxides such as 1,2-dioxolanes, 1,2,4-trioxolanes (ozonides), 1,2-dioxanes, 1,2-dioxenes, 1,2,4-trioxanes, and 1,2,4,5-tetraoxanes. The literature from 2000 onwards is surveyed to provide an update on synthesis of cyclic peroxides. The indicated period of ti...

A facile method, which does not require special equipment, was developed for the preparation of microsized cerium chloride by the thermal treatment of CeCl3·7H2O or the evaporation of its alcoholic solutions. The way of the preparation of the cerium chloride-based catalyst plays a decisive role in its catalytic activity. This catalyst is efficient...

Phosphomolybdic acid (PMA) and phosphotungstic acid (PTA) efficiently catalyze the addition of H2O2 to β-diketones to form bridged 1,2,4,5-tetraoxanes. These reactions are not accompanied by the formation of monocyclic peroxides containing hydroxy and hydroperoxide groups or polymeric peroxides. The use of these catalysts made it possible to obtain...

It was found that oximes undergo deoximation in the presence of the H2O2aq-HBraq system to form ketones and bromo ketones. This reaction provided the basis for the synthesis of dibromo ketones in yields varying from 40% to 94%. This method is environmentally friendly, sustainable, and easy to perform. The results of this investigation extend the po...

Boron trifluoride was found to serve as an efficient catalyst for the reaction of beta,delta-triketones with H2O2 producing tricyclic monoperoxides in yields from 48-93%. BF3 acts simultaneously as a catalyst and co-solvent. The synthesis can be scaled up to tens of grams. The resulting peroxides can be easily isolated from the reaction mixture by...

FIELD: chemistry. ^ SUBSTANCE: present invention relates to a method of producing ketopantolactone, which is widely used in synthesis of pantothenic acid (vitamin B5), as well as other biologically active substances. The method of producing ketopantolactone involves oxidative dehydrogenation of pantolactone under the action of electrochemically gen...