Mulina, Olga Mikhailovna

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.

Grishin S.S., Mulina O.M., Vil' V.A., Terent'ev A.O.

An electrochemical cascade of oxidation/cyclization of pyridine-2-carboxaldehydes with benzylamines involving in situ cyanation with NH4SCN to afford 1-cyano-imidazo[1,5-a]pyridines was developed.

Mulina O.M., Bokova E.D., Doronin M.M., Terent’ev A.O.

Mulina O.M., Doronin M.M., He L., Terent'ev A.O.

Electrochemically induced sulfonylation of alkenes with disulfides as the starting reagents was developed. This transformation is a quite rare example of disulfides usage as S-partners in electrochemical C-S coupling. In...

Budnikov A., Krylov I., Mulina O., Lapshin D., Terent'ev A.

AbstractIn the last decade, free radicals have found a wide application in functionalization of unsaturated compounds, such as alkenes, alkynes, and arenes, via the free‐radical addition to carbon‐carbon π‐bonds. In these processes, intermolecular free‐radical attack on the aromatic substrates represents a challenge due to relatively high resistance of aromatic π‐system to addition reactions in comparison to alkene C=C bonds. The free‐radical functionalization of heterocycles is especially interesting due to the diversity of their structures and chemical properties as well as their importance for medicinal chemistry, agrochemistry, and materials science. Addition of C‐centered radicals to heterocycles is widely known as the Minisci‐type reactions and well‐reviewed. In this paper, we have summarized the main achievements in less explored group of processes: functionalization of heterocycles by intermolecular addition of heteroatom‐centered radicals (O‐, N‐, S‐/Se‐, and P‐radicals) with the emphasis on the papers published after 2010. Literature analysis revealed the strong trend towards the usage of electrochemistry and photoredox‐catalysis for the generation of free radicals in recent years. The remaining fundamental problem in this field is the lack of strong experimental support for the proposed mechanisms and frequent existence of several plausible reaction pathways. The progress in mechanistic studies can significantly improve the prediction of optimal reaction conditions depending on the substrates structure.

Ren S., Zhou Q., Zhou H., Wang L., Mulina O.M., Paveliev S.A., Tang H., Terentʼev A.O., Pan Y., Meng X.

Mulina O.M., Bityukov O.V., Vil’ V.A., Terent’ev A.O.

Paveliev S.A., Segida O.O., Mulina O.M., Krylov I.B., Terent’ev A.O.

Visible light-induced synthesis of enaminones from vinyl azides and aldehydes under decatungstate photocatalysis was developed. The reaction proceeds via acyl radical generation from aldehyde, followed by its addition to vinyl azide, nitrogen elimination, hydrogen atom abstraction by the intermediate iminyl radical, and tautomerization. Photochemical synthesis was efficiently conducted under both batch and flow conditions. The method can be applied to various vinyl azides and aldehydes and provides the desired products in 15-72% yields.

Radulov P.S., Mozzhegorov A.V., Mulina O.M., Yaremenko I.A., Ilovaisky A.I., Terent’ev A.O.

A method was developed for the synthesis of β-triazolyl sulfones from vinylsulfones and 1,2,4-triazoles in the presence of sodium triazolide taken as the base. The reaction was carried out in DMSO at room temperature for 120 h. The target compounds were obtained in 25–89% yields.

Paveliev S.A., Segida O.O., Fedorova U.V., Mulina O.M., Terent'ev A.O.

O,O ′-Bis(phthalimido)-modified 2-(hydroxyimino)ethanols containing N–O–N fragment were synthesized in high yields via the reaction of vinyl azides with N -hydroxyphthalimide under the action of hypervalent iodine-based oxidant. The reaction proceeds under mild conditions and is compatible with a wide range of vinyl azides. Presumably, the process starts with the oxidative formation of phthalimide- N -oxyl radical, followed by its addition to vinyl azide with the subsequent trapping of the generated iminyl radical with the second phthalimide- N -oxyl radical.

Mulina O.M., Doronin M.M., Terent'ev A.O.

A wide range of N -unsubstituted enaminosulfones were obtained via electrochemical sulfonylation of vinyl azides with sulfonyl radicals generated from sodium sulfinates. The discovery of N -unsubstituted enaminosulfones synthesis is based on a unique ability of the azido group to eliminate the N 2 molecule. The process is performed under constant current conditions in an experimentally convenient undivided electrochemical cell equipped with a graphite anode and a stainless steel cathode applying NH 4 I both as the redox catalyst and the supporting electrolyte.

Mulina O.M., Ilovaisky A.I., Terent'ev A.O.

AbstractIndole represents one of the most common and important heterocyclic scaffolds omnipresent in a plenty of natural products and medicinal agents. Development of the synthetic routes to 3‐substituted indoles attracts a considerable attention due to a huge amount of biologically relevant molecules containing 3‐substituted indole moiety. Reactions of indoles halogenation, nitration, acylation, and alkylation at the 3d position have been known for several decades and continue developing now. Processes of indoles sulfenylation are much less studied. However, 3‐sulfenylated derivatives possess promising biological properties. This review summarizes nearly 100 references from the middle of the 20th century to 2021, concerning reactions of indoles sulfenylation mediated by iodine and its compounds. The manuscript is divided into the sections according to the classes of compounds used as sulfenylating agents.

Mulina O.M., Doronin M.M., O. Terent'ev A.

AbstractMn(OAc)3‐mediated sulfonylation of vinyl azides with the use of sodium sulfinates was developed. As a result, N‐enaminosulfones are formed in high yields. The reaction proceeds through the generation of sulfonyl radical, its addition to the double bond of vinyl azide resulting in elimination of N2 molecule and formation of iminyl radical, which is converted on the final step to the desired product. One of the main features of the developed process is application of substoichiometric amount of Mn(OAc)3 due to participation of the generated iminyl radical in the oxidation of the starting sulfinate.

Mulina O.M., Doronin M.M., Kostyagina V.A., Timofeev G.P.

Electrochemical synthesis of gem-bis(sulfenyl)enamines from vinyl azides and thiols is performed. The reaction occurs in an undivided electrochemical cell equipped with platinum electrodes in a DMSO–MeCN solution at a current density of 20 mA/cm2, using NH4I as a supporting electrolyte and a redox catalyst. The yields of the target products are 33–58%.

Mulina O.M., Ilovaisky A.I., Opatz T., Terent'ev A.O.

• Photoredox-catalyzed reaction of vinyl azides and sulfinates gives enaminosulfones. • Eosin Y and PhNO 2 were used as a photocatalyst and an electron shuttle respectively. • Release of N 2 allows the energetically favorable formation of enamine derivatives. • Fluorescence quenching experiments with eosin Y confirmed oxidative quenching route. A metal-free visible light photoredox-catalyzed synthesis of N -unsubstituted enaminosulfones from vinyl azides and sodium sulfinates in moderate to high yields is described. The reaction proceeds in ethanol and uses eosin Y as a readily available photocatalyst in combination with nitrobenzene as an electron shuttle. Taking into account the number of steps involved (generation of the sulfonyl radical, its addition to the double bond, elimination of molecular nitrogen with formation of an iminyl radical, followed by its reduction and protonation) as well as the number of redox-active reaction partners involved, the selectivity of the process is quite impressive.

Qian Z., Zhang Q., Zhao Y., Guan Z., Huang C., He Y.

Dutta J., Ghosh S., Hassan A., De Sarkar S.

Shao J., Liu J., Mei H., Han J.

Bhattacharya D., Studer A.

AbstractThe functionalization of C−H bonds in heterocycles holds considerable importance in chemical synthesis and drug discovery. Recently, the regioselective introduction of various functionalities at the meta‐position of azines, utilizing readily accessible dearomatized intermediates, has emerged as a highly attractive approach. Along these lines, the meta‐hydroxylation of azines is an appealing but challenging transformation due to the inherent electronic nature of these heterocycles. Herein, we report a meta‐selective hydroxylation of pyridines, quinolines and isoquinolines through easily accessible oxazinoaza‐arene intermediates. The nucleophilic C3‐position of these dienamine‐type intermediates engages in highly regioselective hydroxylation upon treatment with electrophilic peroxides.

Bhattacharya D., Studer A.

AbstractThe functionalization of C−H bonds in heterocycles holds considerable importance in chemical synthesis and drug discovery. Recently, the regioselective introduction of various functionalities at the meta‐position of azines, utilizing readily accessible dearomatized intermediates, has emerged as a highly attractive approach. Along these lines, the meta‐hydroxylation of azines is an appealing but challenging transformation due to the inherent electronic nature of these heterocycles. Herein, we report a meta‐selective hydroxylation of pyridines, quinolines and isoquinolines through easily accessible oxazinoaza‐arene intermediates. The nucleophilic C3‐position of these dienamine‐type intermediates engages in highly regioselective hydroxylation upon treatment with electrophilic peroxides.

Bai Y., Xu Z., Sun X., Liang S., Tian H., Sun B., Zeng C.

AbstractAn efficient protocol for the synthesis of thiosulfonates via the electrochemical oxidative sulfonylation of thiols and sodium sulfinates has been developed. The electrochemical oxidative sulfonylation reaction proceeded using NH4I both as a redox catalyst and a supporting electrolyte in undivided cell equipped with graphite anode and graphite cathode under constant current condition. This process avoids the utilization of external oxidants or corrosive molecular iodine and therefore represents an environmentally benign means for achieving the transformation.

Lopat’eva E.R., Krylov I., Terent’ev A.O.

AbstractThe addition of carbon‐centered radicals to double bonds is one of the most atom‐efficient approaches to the formation of new C−C or C−heteroatom bonds. Existing approaches for the generation of carbon‐centered radicals often require elevated temperatures, UV radiation or expensive transition metal catalysts. In this work, a photocatalytic system based on a heterogeneous TiO2 catalyst and a redox organocatalyst N‐hydroxyphthalimide is proposed for the generation of carbon‐centered radicals from C(sp3)−H substrates or aldehydes at room temperature under visible light irradiation. The developed approach was successfully applied to the addition of ethers, alkylarenes and aldehydes to azodicarboxylates. Titanium oxide acts as a photocatalyst, producing phthalimide‐N‐oxyl radicals from N‐hydroxyphthalimide, thereby enabling the organocatalytic process in solution. Phthalimide‐N‐oxyl radicals act as catalytically active species that cleave C−H bonds to form carbon‐centered radicals.

Zhang Z., Wang Y., Pan X., Zhang M., Zhao W., Li M., Zhang H.

A new synthetic method for disulfides and 3-sulfenylchromones is reported. This innovative approach is based on the tetrabutylammonium iodide (TBAI)/H2SO4 reduction system using sodium sulfinate as key component, thus eliminating the need for thiols and redox reagents commonly used in traditional methods. Various disulfides and 3-sulfenylchromones were obtained in moderate to excellent yields through this methodology. Mechanistic studies indicate that thiosulfonates play an important role in the reaction process.

Fomenkov D.I., Budekhin R.A., Mulina O.M., Komarova O., Doronin M.M., Belyakova Y.Y., He L., Yaremenko I.A., Terent'ev A.O.

AbstractOzonolysis of cycloalkanone semicarbazones in alcohol containing solution with the subsequent addition of nickel (II) dithiocarbamates or xanthates was found to result in ω‐xanthyl or ω‐dithiocarbamyl carboxylic acid esters. The reaction proceeds in several steps. The initial one is cycloalkanone semicarbazone ozonolysis in the presence of alcohol, which leads to alicyclic alkoxyhydroperoxide. The second step is an extraordinary interaction between the alkoxyhydroperoxide and nickel (II) dithiocarbamate or xanthate, which proceeds via alkoxy radical formation and its subsequent β‐scission, resulting in C−S coupling products. The developed method allows to obtain ω‐xanthyl or ω‐dithiocarbamyl esters in yields up to 52 % relative to the initial cycloalkanone semicarbazone.

Rao W., Gao C., Jiang L., Ma X., Xu J., Li J., Dong X., Li Y., Zou G.

Grishin S.S., Ustyuzhanin A.O., Vil’ V.A., Terent'ev A.O.

AbstractThe electrochemically mediated cyanation/annulation process with in situ cyanide ion generation from NH4SCN and multi‐step oxidative construction of CN‐functionalized heterocycles from easily available α‐amino esters and pyridine‐2‐carbaldehydes has been discovered. Depending on the nature of the α‐amino ester, 1‐cyano‐imidazo[1,5‐a]pyridine‐3‐carboxylates, 3‐alkyl‐ and 3‐aryl‐imidazo[1,5‐a]pyridines‐1‐carbonitriles, and the first reported 4‐oxo‐4H‐pyrido[1,2‐a]pyrazine‐1‐carbonitriles were obtained. The electrosynthesis is carried out in an undivided electrochemical cell under constant current conditions. The success of the discovered electrochemical synthesis is based on the combination of two anodic processes: oxidation of SCN anion to CN anion and oxidation of C−N bonds to C=N bonds during heterocycle construction. Mechanistic studies based on CV measurements, and control experiments confirm the generation of [CN] species from NH4SCN with subsequent addition to an imine formed from α‐amino esters and pyridine‐2‐carbaldehyde. Computational analysis suggests that for reactive intermediates from glycine esters, the subsequent 5‐endo‐trig cyclization leading to 1‐cyano‐imidazo[1,5‐a]pyridine‐3‐carboxylates is more favourable and the 6‐exo‐trig cyclization leading to 4‐oxo‐4H‐pyrido[1,2‐a]pyrazine‐1‐carbonitriles is less favourable. For α‐amino esters with alkyl or aryl substituents, both cyclization pathways are relatively thermodynamically possible. The leading 4‐oxo‐4H‐pyrido[1,2‐a]pyrazine‐1‐carbonitrile showed high fungicidal activity against phytopathogenic fungi.

Wang J., Ji N., Gao Z., Tang X., Wang L.

Yang Q., Xu R., Ni C., Liu X., Qiao Z., Zhang Q., Wang D., Guo H.

In this work, we developed an efficient, eco-friendly electrochemical three-component one-pot method for the regioselective preparation of polysubstituted 2,5-dihydrofuran-fused spiropyrimidines with valuable –SO2R and –OR functional groups.

Patel M., Panday R., Dholakiya B.Z., Naveen T.

The chalcogen–nitrogen bond (X–N, where X = S, Se) is a key chemical motif in many structures, including inorganic and organic materials, catalysts, protein mimics, and pharmaceuticals.

Zhu C., Mai J., Li X., Shi M., Dong X., Fu H., Shen M., Xu H.

A novel cobalt-catalyzed 1,2-diazidation of 1‑aryl-1,3-dienes by using TMSN3 as azide source has been reported. A series of vicinal diazides containing unsaturated bonds that are amenable to further functionalization were...

Ghosh D., Samal A.K., Parida A., Ikbal M., Jana A., Jana R., Sahu P.K., Giri S., Samanta S.

Abstract(C−X) bonds (X=C, N, O) are the main backbone for making different skeleton in the organic synthetic transformations. Among all the sustainable techniques, electro‐organic synthesis for C−X bond formation is the advanced tool as it offers a greener and more cost‐effective approach to chemical reactions by utilizing electrons as reagents. In this review, we want to explore the recent advancements in electrochemical C−O bond formation. The electrochemically driven C−O bond formation represents an emerging and exciting area of research. In this context, electrochemical techniques offers numerous advantages, including higher yields, cost‐efficient production, and simplified work‐up procedures. This method enables the continuous and consistent formation of C−O bonds in molecules, significantly enhancing overall reaction yields. Furthermore, both intramolecular and intermolecular C−O bond forming reaction provided valuable products of O‐containing acyclic/cyclic analogue. Hence, carbonyl (C=O), ether ‐O‐), and ester (‐COOR) functionalization in both cyclic/acyclic analogues have been prepared continuously via this innovative pathway. In this context, we want to discuss one‐decade electrochemical synthetic pathways of various C−O bond contains functional group in chronological manner. This review focused on all the synthetic aspects including mechanistic path and has also mentioned overall critical finding regarding the C−O bond formation via electrochemical pathways.

Abdukerem D., Chen H., Mao Z., Xia K., Zhu W., Liu C., Yu Y., Abdukader A.

Direct C(sp3)-H selenation, which is most atom economical, remains a formidable challenge, and only a few examples have been reported to date. In this article, we introduce the transition metal-free C(sp3)-H selenation with β-ketosulfones and diselenides as the material source.

Zhang P., Ma J., Liu X., Xue F., Zhang Y., Wang B., Jin W., Xia Y., Liu C.

Chowdhury S., Yadav M.K.

The electrochemical cascade process majorly satisfies the essential criteria of green synthesis. Being an Integrated synthetic strategy it can produce more molecules in a shorter time and thus provides a modern strategic tool in the arsenal of synthetic chemists.

Kuai C., Teng B., Lai R., Zhao Y., Li G., Wu X.

A new method for making use of the catalytic ending PdII-H for the relay-catalytic cycle for dicarbonylation of amines has been developed in a buffer condition, which shows an excellent compatible ability to allow two incompatible catalytic systems working simultaneously in the same catalytic system. This protocol features excellent regioselectivity and broad substrate scope. Our combined experimental and computational studies indicated that the reaction proceeds through a Pd0/PdII-H relay-catalytic cycle.

Wang Y., Dana S., Long H., Xu Y., Li Y., Kaplaneris N., Ackermann L.

Zhang Y., Liu C., Liu J., Li W., Lu H.

.This review summarizes recent developments in electrochemical C–H amination, highlighting key inspirations and proposed mechanisms behind these sustainable oxidation-free approaches for constructing C–N bonds directly from C–H bonds.

Lu Y., Zhang Z., Wu H., Zhou M., Song H., Ji H., Jiang J., Chen J., He W.

The first example of TBAI/H2O cooperative electrocatalytic coupling-annulation of quinoxalin-2(1H)-ones with N-arylglycines was developed. A broad range of tetrahydroimidazo[1,5-a]quinoxalin-4(5H)-ones were obtained in good to excellent yields with exclusive chemoselectivities and excellent regioselectivities. The H-hydrogen bond served as a key factor for the electrocatalytic production of aminomethyl radical at lower oxidative potential.

Yu X., Song S., Zhang Z., Liu Y., Zhang M., Zhu W., Duan G., Zhang P., Ji Y., Xia C.

AbstractCyanoimines (C=N−CN) are eliciting increased attention because of their extensive presence in medicine and biologically active molecules. This study demonstrated the use of the electrochemical oxidative carbon‐atom multifunctionalization and N‐cyanation of imine to synthesize (Z)‐N′‐cyano‐N‐carbamimidothioate. This multicomponent reaction showed good step economy, thereby providing a tool to construct various cyanoimines. Moreover, good functional‐group tolerance and large‐scale synthesis were achieved under metal‐free and external‐oxidant‐free conditions, indicating the potential applicability of this methodology.magnified image

Budnikov A., Krylov I., Mulina O., Lapshin D., Terent'ev A.

AbstractIn the last decade, free radicals have found a wide application in functionalization of unsaturated compounds, such as alkenes, alkynes, and arenes, via the free‐radical addition to carbon‐carbon π‐bonds. In these processes, intermolecular free‐radical attack on the aromatic substrates represents a challenge due to relatively high resistance of aromatic π‐system to addition reactions in comparison to alkene C=C bonds. The free‐radical functionalization of heterocycles is especially interesting due to the diversity of their structures and chemical properties as well as their importance for medicinal chemistry, agrochemistry, and materials science. Addition of C‐centered radicals to heterocycles is widely known as the Minisci‐type reactions and well‐reviewed. In this paper, we have summarized the main achievements in less explored group of processes: functionalization of heterocycles by intermolecular addition of heteroatom‐centered radicals (O‐, N‐, S‐/Se‐, and P‐radicals) with the emphasis on the papers published after 2010. Literature analysis revealed the strong trend towards the usage of electrochemistry and photoredox‐catalysis for the generation of free radicals in recent years. The remaining fundamental problem in this field is the lack of strong experimental support for the proposed mechanisms and frequent existence of several plausible reaction pathways. The progress in mechanistic studies can significantly improve the prediction of optimal reaction conditions depending on the substrates structure.

Kirillov A.S., Semenov E.A., Bityukov O.V., Kuznetsova M.A., Demidova V.N., Rogozhin A.N., Glinushkin A.P., Vil' V.A., Terent'ev A.O.

The electrochemical synthesis of fungicidal thiocyanates from 1,3-dicarbonyl compounds and ammonium thiocyanate was developed. The high efficiency of electrochemical thiocyanation was only achieved using AcOH as the solvent.

Changmai S., Sultana S., Saikia A.K.

Elliott Q., Alabugin I.V.

He M., Zhong P., Liu H., Ou C., Pan Y., Tang H.

The simultaneous binding/dissociation of multiple bonds in a one-pot manner by multicomponent reactions provide an important approach for developing novel and sustainable pathway in the drug discovery process. Herein we develop an electrocatalytic three-component reaction to construct multifunctional and valuable isothiourea compounds, which uses thiols, isocyanides and amines as substrates. Compared with the previous work, the organic electrosynthesis technique can avoid the requirement of heavy metal catalysts and stoichiometric oxidants. In addition, using thiol as a substrate to participate in the three-component reaction broadens the source of sulfur, which can also construct more abundant isothiourea derivatives. As an important synthetic intermediate, isothiourea plays a key role in the fields of agriculture and medicine. We reported an electrocatalytic three-component reaction to construct multifunctional and valuable isothiourea derivatives, which uses thiols, isocyanides and amines as substrates.

He W., Tang L., Jiang J., Li X., Xu X., Yang T., He W.

The first example of paired electrolysis-enabled cyanation of diaryl diselenides, with KSCN as the green cyanating agent, has been developed. A broad range of aryl selenocyanates can be efficiently synthesized under chemical-oxidant- and additive-free, energy-saving and mild conditions.