Electrophilic Cyclization Research Articles

Synthesis of 3,4-Bis(Butylselanyl)Selenophenes and 4-Alkoxyselenophenes Promoted by Oxone®.

We describe herein an alternative transition-metal-free procedure to access 3,4-bis(butylselanyl)selenophenes and the so far unprecedented 3-(butylselanyl)-4-alkoxyselenophenes. The protocol involves the 5-endo-dig electrophilic cyclization of 1,3-diynes promoted by electrophilic organoselenium species, generated in situ through the oxidative cleavage of the Se-Se bond of dibutyl diselenide using Oxone® as a green oxidant. The selective formation of the title products was achieved by controlling the solvent identity and the amount of dibutyl diselenide. By using 4.0 equiv of dibutyl diselenide and acetonitrile as solvent at 80 °C, four examples of 3,4-bis(butylselanyl)selenophenes were obtained in moderate to good yields (40–78%). When 3.0 equiv of dibutyl diselenide were used, in the presence of aliphatic alcohols as solvent/nucleophiles under reflux, 10 3-(butylselanyl)-4-alkoxyselenophenes were selectively obtained in low to good yields (15–80%).

Synthesis of 2‐Aryl‐(3‐Organochalcogenyl)Thieno[2,3‐b]Pyridines Promoted by Oxone®

AbstractWe describe herein an alternative method for the synthesis of 2‐aryl‐(3‐organochalcogenyl)thieno[2,3‐b]pyridines through the electrophilic cyclization of 3‐(arylethynyl)‐2‐(alkylthio)pyridines promoted by electrophilic species of organochalcogen compounds. These species were generated in situ by the oxidative cleavage of chalcogen‐chalcogen (Se, Te) bond of diorganyl dichalcogenides using Oxone® in ethanol as solvent in an open‐flask at 78 °C. The protocol allowed the synthesis of highly substituted thieno[2,3‐b]pyridines starting from several diorganyl dichalcogenides and 3‐(arylethynyl)‐2‐(alkylthio)pyridines, obtaining 21 new compounds in good to excellent yields (70–99%). Still, the method showed good efficiency on the gram‐scale synthesis. In addition, several synthetic transformations such as oxidation, selenylation and hydrogenation reactions were demonstrated.

Design of 2-(4-(2-pentyllbenzo[b]thiophen-3-yl)benzylidene)malononitrile based remarkable organic catalyst towards hydrazine electrooxidation

Abstract Herein, 2-(4-(2-pentyllbenzo[b]thiophen-3-yl)benzylidene)malononitrile (6B) is synthesized by using coupling reactions, electrophilic cyclization reactions, and condensation reactions. Then, these materials are employed as anode catalysts for hydrazine electrooxidation reactions with electrochemical methods such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) in 1 M KOH + 0.5 M N2H4 solution on different benzothiophene derivates. 6B catalyst exhibits the best catalytic activity in hydrazine electrooxidation reaction with 3.22 mA cm−2 (16.72 mA mg−1 6B) value. Thus, for the electrodes obtained from 6B, the electrode preparation stage is optimized by the response surface methodology (RSM) and the hydrazine electrooxidation current under optimum conditions is found as 4.95 mA cm−2. EIS results reveal that 6B modified electrode has the lowest charge transfer resistance. In conclusion, 6B catalyst could be used as anode catalysts in hydrazine fuel cells instead of expensive catalysts such as Pt, Pd, and Au.

Silver/Rhodium Relay Catalysis Enables C−H Functionalization of In Situ Generated Isoquinolines with Sulfoxonium Ylides: Construction of Hexahydrodibenzo[a,g]quinolizine Scaffolds

AbstractEmploying silver/rhodium relay catalysis strategy, an intramolecular electrophilic cyclization and C−H activation followed by cascade hydrogenation and reductive amination has been developed. The acylmethylated isoquinoline derivatives could be afforded with broad substrate scope in 23–88% yields, which could be further transformed to the core skeleton of hexahydrodibenzo[a,g]quinolizine as drug‐candidates. Moreover, this reaction was achieved in a gram‐scale. A reasonable reaction mechanism has been proposed based on a series of control and KIE experiments.magnified image

Synthesis of 4-Selanyl- and 4-Tellanyl-1H-isochromen-1-ones Promoted by Diorganyl Dichalcogenides and Oxone

A new method was developed for the synthesis of 4-chalcogenyl-1H-isochromen-1-ones through the 6-endo-dig electrophilic cyclization of 2-alkynylaryl esters and diorganyl dichalcogenides under ultrasound irradiation. The reactions were performed under mild conditions, using Oxone as a green oxidant to promote the cleavage of the chalcogen-chalcogen bond in diorganyl diselenides and ditellurides to generate electrophilic species in situ. A total of 25 compounds were selectively obtained after 30-70 min, in good to excellent yields (74-95%). This procedure was extended to prepare 5H-selenopheno[3,2-c]isochromen-5-ones. Additionally, for the first time, the 4-chalcogenyl-1H-isochromen-1-ones were used as substrates in the thionation reaction, using Lawesson's reagent and microwave irradiation under solvent-free conditions, obtaining the thio derivatives in yields of up to 99% in only 15 min.

From a 1,2-azaborinine to largeBN-PAHsviaelectrophilic cyclization: synthesis, characterization and promising optical properties

A synthetic approach towards boron-nitrogen substituted polycyclic aromatic hydrocarbons (BN-PAHs)viaelectrophilic cyclization is described and it is shown that the variation of the rings' connectivity may tune the emission wavelengths effectively.

Novel Tandem Three Consecutive Reactions: Aza-Wittig, Imine Condensation and Electrophilic Aromatic Substitution Strategy to Indolizine Synthesis

Reaction of ethyl (Z)-3-(heteroaryl/aryl)-2-((triphenyl-λ5-phosphaneylidene) amino) acrylates intermediates with 2,3-thiophenedicarboxaldehyde was used in novel Tandem three consecutive reactions: aza-Wittig, imine condensation and electrophilic heteroaromatic cyclization to obtain a series of indolizines. A tentative mechanism of this reaction is proposed.

Electrophile promoted cyclization of ortho-aryl substituted ynamides: construction of 3-amino-4-halo- or 4 seleno-isocoumarin derivatives.

Isocoumarins are important building blocks in medicinal chemistry. They are widespread in the core structure of biologically active compounds. Here we report the development of an efficient and highly reactive electrophilic cyclization of ortho-ynamidyl benzoate esters providing access to 3-amino-4-halo- or 4-seleno-isocoumarins in a short time (<1 min) with good yields.

Iodine mediated cascade oxidative functionalization, cyclisation and annulation reactions

Molecular iodine has a huge application in the field of electrophilic cyclisation reactions, oxidation, oxidative cyclisation, multi-component reactions, ring opening, cyclisation, rearrangement, oxidative cross coupling, oxidative annulation, C-H functionalization reactions, synthesis of heterocycles and its derivatives. In this mini review I discuss the utilization of iodine mediated cascade reactions for oxidative annulation, functionalization and cyclisation of various organic compounds.

Oxone-Promoted Synthesis of 4-(Chalcogenyl)isoquinoline-N-oxides from Alkynylbenzaldoximes and Diorganyl Dichalcogenides.

We report a protocol for the synthesis of 3-organyl-4-(organylchalcogenyl)isoquinoline-2-oxides via electrophilic cyclization between alkynylbenzaldoximes and diorganyl dichalcogenides promoted by Oxone. A total of 21 3-organyl-4-(organylchalcogenyl)isoquinoline-2-oxides were selectively obtained in yields of up 93% under an ultrasound irradiation condition in short reaction times (10-70 min). Additionally, the synthetic usefulness of the 3-phenyl-4-(phenylselanyl)isoquinoline-2-oxide was demonstrated in the annulation reaction with 1-(2-bromophenyl)-3-phenylprop-2-yn-1-one and in the deoxygenation reaction with phenylboronic acid.

Access to a Phthalazine Derivative Through an Angular cis-Quinacridone.

Intramolecular electrophilic cyclization of a bisanthranilate afforded an angular cis-quinacridone compound, which condensed with hydrazine to give a phthalazine derivative. A [2+2+2] cyclization reaction occurred at the C-N double bond position of phthalazine when reacted with dimethyl acetylenedicarboxylate. The structures of these novel compounds were confirmed by crystallographic analysis. The phthalazine derivative decomposes back to quinacridone at ambient condition in the dark and as a solid with a half lifetime of about 22 months.

A facile synthesis of 6-[(4-nitrophenyl)thio]-substituted 2-methylene-2,3-dihydro-1,4-oxazepines from N-propargylic β-enaminones

A one-pot process for the synthesis of 6-[(4-nitrophenyl)thio]-substituted 2-methylene-2,3-dihydro-1,4-oxazepines is reported. When reacted with 4-nitrobenzenesulfenyl chloride, N-propargylic β-enaminones afforded α-sulfenylated N-propargylic β-enaminones, which, in the presence of zinc chloride, underwent electrophilic cyclization to yield 6-[(4-nitrophenyl)thio]-substituted 2-methylene-2,3-dihydro-1,4-oxazepines. Process was found to be general for various N-propargylic β-enaminones along with large substrate scope and high functional group tolerance. This operationally easy method may provide quick access to a library of functionalized 1,4-oxazepines of pharmacological interest.

Iodocyclisation of Electronically Resistant Alkynes: Synthesis of 2-Carboxy (and sulfoxy)-3-iodobenzo[b]thiophenes

The iodocyclisation of alkynes bearing tethered nucleophiles is a highly effective method for the construction and diversification of heterocycles. A key limitation to this methodology is the 5-endo-dig iodocyclisation of alkynes that have an unfavourable electronic bias for electrophilic cyclisation. These tend to direct electrophilic attack of the iodonium atom to the wrong carbon for cyclisation, thus favouring competing addition reactions. Using our previously determined reaction conditions for the 5-endo-dig iodocyclisations of electronically resistant alkynes, we have achieved efficient synthetic access to 2-carboxy (and sulfoxy)-3-iodobenzo[b]thiophenes. The corresponding benzo[b]furans and indoles were not accessible under these conditions. This difference may arise due to the availability of a radical mechanism in the case of iodobenzo[b]thiophenes. The 2-carboxy functionality of the iodocyclised products can be further employed in iterative alkyne-coupling iodocyclisation reactions, where the carboxy group or an imine (Schiff base) partakes in a second iodocyclisation to generate a lactone or pyridine ring.

A facile synthesis of 6-chloro-2-methylene-2,3-dihydro-1,4-oxazepines from N-propargylic β-enaminones

A new and efficient method for the synthesis of 6-chloro-substituted 2-methylene-2,3-dihydro-1,4-oxazepines has been demonstrated. Upon treatment with N -chlorosuccinimide in acetonitrile, N -propargylic β-enaminones underwent chlorination to afford α-chlorinated N -propargylic β-enaminones, which was then subjected to electrophilic cyclization with zinc chloride in refluxing chloroform to yield 6-chloro-2-methylene-2,3-dihydro-1,4-oxazepines. It was shown for the first time that on N -propargylic β-enaminone systems, α-chlorination exclusively preponderates over the formation of chloronium ion. The method was found to be general for a diversity of N -propargylic β-enaminones and tolerated the presence of a wide range of aryl, heteroaryl and alkyl groups with electron-donating and electron-withdrawing substituents. The method was also applicable as the one-pot two-step process without isolating the intermediate α-chlorinated N -propargylic β-enaminones. This operationally easy method may provide a rapid entry to a library of highly functionalized 6-chloro-2-methylene-2,3-dihydro-1,4-oxazepines with potential medicinal applications for human health. • A new and practical method for synthesis of 6-chloro-substituted 1,4-oxazepines. • One-pot conversion of N-propragyl β-enaminones to 6-chloro-substituted 1,4-thiazepines. • High efficiency, large substrate scope and broad functional group tolerance. • Synthesis of chlorine-bearing 1,4-thiazepines as potential scaffolds and pharmacophores.

Regioselectivity of Intramolecular Electrophilic Cyclization of 2-(Alkenylsulfanyl)thieno[2,3-d]pyrimidin-4(3H)-ones with p-Methoxyphenyltellurium Trichloride

3-Phenyl-2-(prop-2-en-1-ylsulfanyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one reacted with 4-methoxyphenyltellurium trichloride in a regioselective manner to give angularly fused 1-{[dichloro(4-methoxyphenyl)-λ4-tellanyl]methyl}-4-oxo-5-phenyl-1,2,4,5,6,7,8,9-octahydrobenzo[4,5]thieno[3,2-e][1,3]thiazolo[3,2-a]pyrimidinium chloride. Electrophilic cyclization of 2-(prop-2-en-1-ylsulfanyl)- and 2-(2-methylprop-2-en-1-ylsulfanyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-ones with 4-methoxyphenyltellurium trichloride afforded linearly fused 3-{[dichloro(4-methoxyphenyl)-λ4-tellanyl]methyl}-2,3,6,7,8,9-hexahydro-5H-benzo[4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]pyrimidin-5-one hydrochlorides. Regardless of the reactant ratio, the products were isolated as 1:1 complexes with 4-methoxyphenyltellurium trichloride.

Development of Heterocycle-Substituted and Fused Azulenes in the Last Decade (2010-2020).

Azulene derivatives with heterocyclic moieties in the molecule have been synthesized for applications in materials science by taking advantage of their unique properties. These derivatives have been prepared by various methods, involving electrophilic substitution, condensation, cyclization, and transition metal-catalyzed cross-coupling reactions. Herein, we present the development of the synthetic methods, reactivities, and physical properties for the heterocycle-substituted and heterocycle-fused azulenes reported in the last decade.

Asymmetric Spirocyclization Enabled by Iridium and Brønsted Acid-Catalyzed Formal Reductive Cycloaddition

A catalytic, enantioselective spirocyclization of formanilides or formylindolines and enamides has been developed herein. The reaction proceeds through a sequential iridium-catalyzed hydrosilylatio...

Trifunctionalized Allenes. Part IV. Cyclization Reactions of 4-Phosphorylated 5-Hydroxyhexa-2,3-dienoates

This manuscript focuses on the reactions of 4-phosphorylated 5-hydroxyhexa-2,3-dienoates with protected or unprotected hydroxy groups involving 5-endo-trig cyclizations. Reactions with electrophiles result in mixtures of the 2,5-dihydro-1,2-oxaphosphole-5-carboxylates and the 5-phosphorylfuran- 2(5H)-ones by competitive electrophilic cyclization due to the neighboring phosphonate (phosphine oxide) and the carboxylate groups participation. 4-Phosphorylated 5-hydroxyhexa-2,3-dienoates were smoothly transformed into the corresponding 4-phosphoryl-2,5-dihydrofuran-2-carboxylates by using 5 mol % of a silver salt as a catalyst in the 5-endo-trig cycloisomerization reaction.

Dichalcogenides/Oxone®‐Mediated Cyclization of (Z)‐Chalcogenoenynes under Ultrasound Irradiation

Abstract3‐Selanyl‐ and 3‐tellanylchalcogenophenes were prepared by the electrophilic cyclization of (Z)‐chalcogenoenynes under ultrasound irradiation conditions. This green procedure was carried out using Oxone® as an inexpensive and non‐toxic oxidant agent to promote the oxidative cleavage of Se−Se and Te−Te bonds. The electrophilic cyclization of (Z)‐1‐propylthio‐ and (Z)‐1‐butylselen‐1‐en‐3‐ynes was performed using the diaryl diselenide or ditelluride/Oxone®/ethanol system. The respective 3‐arylselanyl and 3‐aryltellanylthiophenes and selenophenes were obtained in 40 % to 87 % yield (16 examples). Similarly, 3‐arylselanyl and 3‐aryltellanyltellurophenes were synthesized by the cyclization of (Z)‐1‐butyltelluro‐1‐en‐3‐ynes, using glycerol as the solvent instead ethanol (5 examples; 28 % to 65 % yield). For the first time, Oxone® was used in the selective oxidative cleavage of the Te−Te bond in cyclization reactions.

Synthesis of Seleno‐Heterocycles via Electrophilic/Radical Cyclization of Alkyne Containing Heteroatoms

Abstractcontaining heterocyclic scaffolds by virtue of their interesting reactivities and a broad range of applications in the medicinal and materials chemistry. This review involves the electrophilic/radical cyclization of alkynes containing heteroatoms which resulted into the novel Se‐heterocycles. The synthesis of seleno‐heterocycles via different nucleophiles including O, N, S, Se, Te, and C‐nucleophiles is exhaustively discussed. Also, one‐pot electrophilic cyclization of 1,3‐diynes and 1,3,5‐triynes was described in details. Furthermore, the various mechanisms underlying the synthesis of selenium‐β‐lactam, carbapenem heterocycle, bis‐ and tris‐selenide alkene, β‐selenosulfonation and selenated alkynes were discussed. The Se‐heterocycles reported in this review allow preparing these selenated compounds bearing the selenium moiety both on the rings (outside) and inside the ring (e. g. selenophenes). The review demonstrates the growing opportunities to construct selenium containing heterocycles from alkynes containing heteroatoms.magnified image