Electrophilic Cyclization Research Articles

Developments in the Construction of Benzo[b]thiophenes from 2‐Alkynylthioanisoles by Electrophilic and Radical Cyclization Reactions

Developments in the Construction of Benzo[b]thiophenes from 2‐Alkynylthioanisoles by Electrophilic and Radical Cyclization Reactions

Synthesis of Trifluoromethylselenolated Spiro[5.5]trienones/Spiro[4.5]trienones via Electrophilic Trifluoromethylselenolation Cyclization and Dearomatization

An expedient strategy for the construction of trifluoromethylselenolated spiro[5.5]trienones/spiro[4.5]trienones through a cascade electrophilic trifluoromethylselenolation cyclization and dearomatization has been developed. This sequential process was induced by N‐trifluoromethylselenophthalimide (Phth‐SeCF3), which was an efficient electrophilic trifluoromethylselenolation reagent. This approach has the feature of mild conditions, broad substrate scope, and high functional group tolerance.

Synthesis of Dihalonaphthalenes via Silver-Catalyzed Halogenation and Electrophilic Cyclization of Terminal Alkynols.

Herein, we report a silver-catalyzed halogenation and electrophilic cyclization reaction based on the trifunctionalization of terminal alkynols with NBS or iodine monochloride in a step-efficient synthetic way to produce homo/heterodihalogenated naphthalene derivatives bearing two different halogen atoms in moderate to good yields. This methodology readily accommodates various functional groups, including electron-withdrawing nitro, cyano, acid-sensitive dioxazolyl, and alkoxy groups.

Recent Developments in Selenylation of Alkynes

Alkynes are simple yet important organic feedstocks. The selenylation of alkynes is able to produce complex selenium‐containing compounds in a facile way. Although there are some reviews about the selenylation of alkynes, most of them focus on one specific reaction or what types of products that can be obtained. There is a lack of attention given to the various uses of different selenium reagents and their mechanisms. This review mainly focuses on recent advances (2013‐2023) based on diverse selenium reagents. Mechanisms and how the added reagents work will be discussed. Different reaction types, including difunctionalization, Se‐annulation, spiro‐cyclization, C‐Se coupling, click reaction will be recorded in this review. The regioselectivity can be achieved through various mechanisms, including radicals, seleniraniums or electrophilic cyclization. We hope it will do help for future research in this area.

SYNTHESIS OF BENZO[B]THIOPHENE-BASED ORGANIC COMPOUNDS AND THEIR HYDRAZINE ELECTROOXIDATION PERFORMANCE AS AN ANODE CATALYST

In this study, 3-iodo-2-(p-tolyl)benzo[b]thiophene (4C) is synthesized by using Sonagashira coupling reactions and electrophilic cyclization reactions. Electrochemical measurements have been performed using electrochemical methods such as cyclic voltammetry (CV), chronoamperometry (CA) and electrochemical impedance spectroscopy (EIS) in the environment of 1 M KOH + 0.5M N2H4 solution. The CV results obtained showed that 4C catalyst promoted the generation of the best current (15.40 mA/cm2), and EIS results confirmed that electrode modifeed with the same derivative presented the lowest charge transfer resistance. Taken together, these results suggest that 4C organocatalyst could be used as an anode efficient catalyst in hydrazine (N2H4) fuel cells.

Pd(II)/LA‐Catalyzed Intramolecular Hydroarylation of Alkynoates to Construct Coumarins

AbstractTransition‐metal ions catalyzed intramolecular hydroarylation of aryl alkynoates to construct coumarin skeletons is merited for its step and atom‐economic advantages when compared with other methodologies. The challenge is that the electrophilic cyclization of this reaction requires the strong electrophilic capability of the catalyst, which makes this methodology was seldomly developed after its early explorations. Herein, we report a Lewis acid promoted Pd(II)‐catalyzed intramolecular hydroarylation to construct coumarin and its derivatives; the linkage of Lewis acid to the Pd(II) species through diacetate bridge improved its electrophilic capability, facilitating the hydroarylation reaction happening under the neutral conditions.

Electrophilic aryl spiroannulation induced by diaryliodonium salts: efficient synthesis of [5,5]-spiro lactone-lactam scaffolds from α-cyanocarboxylates

Spirocyclic architectures represent one of the privileged three-dimensional scaffolds in pharmaceutical chemistry and drug discovery, while the new-skeletal synthesis of spiromolecules from simple starting materials remains a challenging task. Here, we report a first diaryliodonium salts mediated electrophilic aryl spiroannulation reaction from simple substrates α-cyanocarboxylate. With this strategy, a broad spectrum of new [5,5] spiro-fused skeletons could be efficiently constructed in one step via Cu-catalyzed cascaded N-arylation-acylation and etheral skeleton rearrangement reaction. The key point of this transformation was the intramolecular electrophilic cyclization due to the nucleophilicity of O-atom and electrophilicity of α-C induced by diaryliodonium salts. With this protocol, the more challenging activation of ether bonds was achieved via diaryliodonium salts-mediated. This method has the major advantages of a broad substrate scope and excellent functional group compatibility. Further synthesis elaboration was performed using substrate with steric hindrance to showcase the versatility of this methodology.

Design of highly effective organic catalyst for hydrazine electrooxidation: Iodobenzo[b]furan derivatives

In this study, we investigate the electrochemical characteristics of 2-aryl/alkyl-3-iodobenzo[b]furans as anode catalysts for hydrazine (N2H4) fuel cells. Cyclic voltammetry (CV), chronoamperometry (CA) and electrochemical impedance spectroscopy (EIS) techniques are employed to investigate the performance of these heteroaromatic compounds. The results demonstrate the promising potential of the 2-aryl/alkyl-3-iodobenzo[b]furans in fuel cell technology. Among the tested organic catalysts (2a, 2b, 2c, 2d, and 2e), 2a exhibited the highest electrocatalytic activity, giving a total current density of 26.62 mA/cm2 within the potential range of −0.4 to −0.8 V. 2-aryl/alkyl-3-iodobenzo[b]furans were synthesized by using palladium/copper-catalyzed Sonogashira cross-coupling reactions, followed by electrophilic cyclization with iodine (I2). All products were characterized using 1H and 13C NMR spectroscopy, confirming their structures and providing insights into their chemical properties.

Hydrazine electrooxidation performance of cyano-substituted indole derivatives as organic anode catalyst

Here we present the new EWG-substituted indole derivatives, namely 2-((5-(1-methyl-2-phenyl-1 H-indol-3-yl)thiophen-2-yl)methylene) malonitrile (IPTM), 2-((5-(1-methyl-2-phenyl-1 H-indol-3-yl)furan-2yl)methyl)malonitrile(IPFM) and 2-((4-(1-methyl-2-phenyl-1 H-indol-3-yl)benzylidene) malonitrile (IPPM) was synthesized by using Sonogashira coupling, electrophilic cyclization, Suzuki-Miyaura coupling and condensation reactions. The isolated yields were obtained as 86 %, 71 %, and 69 % yields, respectively. Cyclic voltammetry(CV), chronoamperometry (CA), and electrochemical impedance spectroscopy (EIS) were used for the electrochemical measurements to observe the electrocatalytic behavior of IPTM, IPFM and IPPM. The results exhibited that the highest-performance organic-based catalyst was 2.601 mA/cm2 (0.073 mA/mg) for IPPM which could be a good candidate as a metal-free electrocatalyst for hydrazine electrooxidation.

Temperature-Controlled Divergent Synthesis of Pyrazoles and 1-Tosyl-1H-pyrazoles under Transition-Metal-Catalyst- and Oxidant-Free Conditions.

Herein, a general and practical temperature-controlled approach for the divergent synthesis of pyrazoles and 1-tosyl-1H-pyrazoles via electrophilic cyclization in the absence of transition-metal catalysts and oxidants was developed. The desired products were obtained in moderate to excellent yields from common starting materials in both ionic liquids and ethanol by simply tuning the reaction temperature. This strategy employs easily synthesized substrates, mild reaction conditions, and excellent functional-group tolerance.

Pd-Catalyzed Chelation-Assisted Regioselective and Site Selective Cyclative C-H Annulation of Alkynyl Oximes with Activated Alkynes.

Electrophilic cyclization and concomitant C-H annulation constitute an expedient cascade strategy for the construction of multicyclic scaffolds with precise substitutional patterns. We report here a novel Pd-catalyzed cyclative annulation of ynone oxime with activated alkynes. The cascade features a dual regioselectivity including site selective C-H activation and chelation-assisted selective insertion of alkynes. Control experiments together with kinetic experiments give insights into the mechanism.

Pd-Catalyzed Sequential Electrophilic Cyclization/Selective C-H Annulation Cascade: Synthesis of Isoxazole-Phthalimide-Fused Poly-Heterocyclics.

Harnessing the organo-palladium intermediates generated from electrophilic cyclizations for tandem C-C bond construction is a challenging task but constitutes an excellent tool for constructing complex motifs from simpler substrates. We realize herein such a cyclative annulation of alkynyl-oxime ethers with maleimides for the facile construction of isoxazole-phthalimide hybrid motifs through Pd(II) catalysis. This protocol features excellent regio-selectivity in C-H selection, a broad substrate scope, good functional group tolerance, and scalability. Necessary KIE & labeling studies give insight into the reaction mechanism.

Synthesis of Selenocyanated Indoles via PhICl2‐Induced Electrophilic Intramolecular Cyclization of 2‐Alkynylanilines or 2‐Alkenylanilines

AbstractThe 3‐selenocyanato‐substituted indoles were readily synthesized via (dichloroiodo)benzene (PhICl2)‐induced reaction of 2‐alkynylanilines or 2‐alkenylanilines with KSeCN in MeCN under metal‐free conditions. The reaction sequence was postulated to encompass the formation of a reactive selenocyanogen chloride species, generated in situ from the reaction of PhICl2 and KseCN, followed by electrophilic addition and intramolecular cyclization steps.

Kaliendina S., Brynzei M., Kut M., Sukharev S.M., Ostapchuk Е., Onysko M. REGIOSELECTIVITY OF ALKYLATION OF 2-(THIOPHENE-2-IL)THIENO[2,3 d]PYRIMIDINE-4(3H)-ONE

Thieno[2,3-d]pyrimidines are an important class of heterocyclic compounds with a wide range of biological activities. The thieno[2,3-d]pyrimidin-4-one system is of the greatest interest to scientists, as it is one of a large number of possible thienopyrimidine derivatives. The presence of an amide fragment in these molecules allows for the introduction of various substituents via alkylation reactions. On the other hand, the presence of N- and O-nucleophilic centres makes it possible to form different types of alkylation products.
 In the present work, the alkylation reaction of 5,6-dimethyl-2-(thiophen-2-yl)thieno[2,3-d]pyrimidin-4(3H)-one, which contains N(3)- and O-nucleophilic centres for attacking alkylating reagents, was investigated. Allyl bromide was used as an alkylating reagent. It was found that the alkylation of 5,6-dimethyl-2-(thiophen-2-yl)thieno[2,3-d]pyrimidin-4(3H)-one with allyl bromide in DMF resulted in the regioselective preparation of 4-(allyloxy)-5,6-dimethyl-2-(thiophen-2-yl)thieno[2,3-d]pyrimidine, which can be used in the future to study the process of electrophilic intramolecular cyclisation. An increase in the reaction time of the starting reagents leads to an increase in the yield of the target ester.
 Keywords: 5,6-dimethyl-2-(thiophen-2-yl)thieno[2,3-d]pyrimidin-4(3H)-one; alkylation; regioselectivity; ether; 4-allyloxypyrimidine.

Meldrum’s acid assisted formation of tetrahydroquinolin-2-one derivatives a short synthetic pathway to the biologically useful scaffold

A new method for the preparation of tetrahydroquinolin-2-one derivatives is presented. This approach involves a two-step reaction between enaminones and acylating agents, immediately followed by electrophilic cyclization, all within a single synthesis procedure, eliminating the need to isolate intermediates. The entire process is facilitated by the use of acyl Meldrum’s acids which not only shortens the preparation time of the substrates but also easily extends the range of substituents That can be used. The method’s scope and limitations were evaluated with various reagent combinations thus demonstrating its general applicability to the synthesis of tetrahydroquinolin-2-one core. Interestingly, some exceptions to the regular reaction pathway were observed when a strong EDG (electron donating group) was introduced via acyl Meldrum’s acids. The underlying mechanism of this phenomenon was elucidated during the investigation.

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes.

Eunicellane diterpenoids are a unique family of natural products containing a foundational 6/10-bicyclic framework and can be divided into two main classes, cis and trans, based on the configurations of their ring fusion at C1 and C10. Previous studies on two bacterial diterpene synthases, Bnd4 and AlbS, revealed that these enzymes form cis- and trans-eunicellane skeletons, respectively. Although the structures of these diterpenes only differed in their configuration at a single position, C1, they displayed distinct chemical and thermal reactivities. Here, we used a combination of quantum chemical calculations and chemical transformations to probe their intrinsic properties, which result in protonation-initiated cyclization, Cope rearrangement, and atropisomerism. Finally, we exploited the reactivity of the trans-eunicellane skeleton to generate a series of 6/6/6 gersemiane-type diterpenes via electrophilic cyclization.

γ-Hydroxy-γ-butyrolactams as 1,2-bis-electrophiles in a Brønsted/Lewis acid-free synthesis of condensed nitrogen heterocycles

Here, we describe the one-pot assembly of imidazo[1,2-a]pyridine and quinoxaline heterocyclic cores by the electrophilic tandem cyclization between 3,5-diaryl substituted 5-hydroxy-3-pyrrolin-2-ones and the corresponding nitrogen bis-nucleophiles.

DMTSF-mediated electrophilic cyclization for the synthesis of 3-thiomethyl-substituted benzo[b]furan derivatives.

Benzofuran is an important backbone for molecules that make up several pharmaceuticals, herbicides/pesticides, and organo-electronics. An environmentally benign dimethyl(methylthio)sulfonium tetrafluoroborate salt was used as an electrophile to induce cyclization of o-alkynyl anisoles to form 2,3-disubstituted benzofurans. The cyclization is performed at ambient reaction conditions, only takes 12 hours to get excellent yields, and shows a high tolerance for various substituted alkynes. Also, a sulfurmethyl group obtained after the cyclization reactions allows for a cascade cyclization, and an alkyne is used in the reaction to create a thieno[3,2-b]benzofuran core structure.

Facile synthesis of dibenzothiophene S-oxides from sulfinate esters.

An efficient method to prepare dibenzothiophene S-oxides is disclosed. Suzuki-Miyaura cross-coupling of 2-bromoaryl sulfinate esters with arylboronic acids selectively at the bromo group followed by electrophilic cyclization of the resulting sulfinate ester moiety provides diverse dibenzothiophene S-oxides. Further transformations including Pummerer-type C-H propargylation and aryne reactions realize to synthesize highly functionalized dibenzothiophene derivatives.

Investigation of the performance of (4-(3-iodobenzo[b]thiophen-2-yl)-N,N-dimethyllaniline as an anode catalyst for glucose electrooxidation

In this study (4-(3-iodobenzo[b]thiophen-2-yl)-N,N-dimethyllaniline (4), Sonagashira Coupling Reaction was synthesized using Electrophilic Cyclization Reactions. Then, the anode catalyst performance for glucose electrooxidation was investigated. The electrocatalytic activities of the organic catalyst were investigated by CV, CA and EIS measurements in 1 M KOH + 0.5 M C6H12O6 solution. Interestingly, electrochemical depositing on organic catalyst by Pd metal increased the specific activity, and it was calculated as 0.61 mA/cm2 Consequently, Pd@4 catalyst will be used as an electrocatalyst with high specific and stability and low charge transfer activity.