Intramolecular Cyclization Reaction Research Articles

Organocatalyzed Photoelectrochemistry for the Generation of Acyl and Phosphoryl Radicals through Hydrogen Atom-Transfer Process.

An organocatalyzed photoelectrochemical method for the generation of acyl and phosphoryl radicals from formamides, aldehydes, and phosphine oxides has been developed. This protocol utilizes 9,10-phenanthrenequinone (PQ) as both a molecular catalyst and a hydrogen atom-transfer (HAT) reagent, eliminating the requirement for external metal-based reagents, HAT reagents, and oxidants. The generated acyl radicals can be applied to a range of radical-mediated transformation reactions, including C-H carbamoylation of heteroarenes, intermolecular tandem radical cyclization of CF3-substituted N-arylacrylamides, as well as intramolecular cyclization reactions. The use of acyl radicals in these transformations offers an efficient and sustainable approach to accessing structurally diverse carbonyl compounds.

Pd(0)-Catalyzed Intermolecular Methylene C(sp3)-H Silylation by Using N-Heterocyclic Carbene Ligands.

The direct functionalization of methylene C(sp3)-H bonds is one of the greatest challenges in transition metal-catalyzed C-H activation. Although Pd(0)-catalyzed intramolecular cyclization reactions of methylene C(sp3)-H bonds have been reported, intermolecular functionalization remains to be discovered. Herein, we report the first example of a Pd(0)-catalyzed intermolecular methylene C(sp3)-H functionalization reaction. By use of a N-heterocyclic carbene ligand, the methylene C(sp3)-H bonds of 1-(benzyloxy)-2-iodobenzenes are activated and disilylated with hexamethyldisilane, affording disilylated products.

3+3] Annulation of Diazoenals and α-Mercapto Ketones via Protic Sulfonium Ylides: Direct Synthesis of 2H-Thiopyrans, Innovative Progenitors for Unstudied 2H-Thiopyran-2-ones and 4H-Thiopyran-4-ones.

Herein, we report a new Rh(II)/Sc(III)-catalyzed [3+3] annulation between diazoenals and α-mercapto ketones for the direct synthesis of 4-formyl-2H-thiopyrans. The reaction proceeds via protic sulfonium ylides derived from highly electrophilic Rh-enalcarbenoids, followed by regioselective intramolecular aldol condensation. Further studies revealed that 4-formyl-2H-thiopyrans are novel precursors for unstudied 2H-thiopyran-2-ones and 4H-thiopyran-4-ones. The 4H-thiopyran-4-ones were obtained via a novel O2/Et3N-mediated oxidative deformylation. This methodology was applied to the short synthesis of structurally complex pyrimidine-fused 2H-thiopyran via cascade Schmidt, Ritter, and intramolecular cyclization reactions.

Formation, Selective Encapsulation, and Tautomerization Control of Isoindolone Utilizing Guanidinium Sulfonate Frameworks.

Herein we report the use of tetrakis (guanidinium) pyrenetetrasulfonate (G4PYR) and bis (guanidinium) 1,5-napthalene disulfonate (G2NDS) to catalyze the cyclization of 2-cyanobenzamide (1) to isoindolone (2). Moreover, we demonstrate the remarkable selectivity of these guanidinium organosulfonate hosts in encapsulating 2 over 1. By thoroughly investigating the intramolecular cyclization reaction, we determined that guanidinium and the organosulfonate moiety acts as the catalyst in this process. Additionally, 2 is selectively encapsulated, even in mixtures of other structurally similar heterocycles like indole. Furthermore, the tautomeric state of 2 (amino isoindolone (2-A) and imino isoindolinone forms (2-I)) can be controlled by utilizing different guanidinium organosulfonate frameworks.

Photocatalytic alkenes to ring-fused quinazolin-4(3H)-ones via proton-transfer shuttle using TFA

Herein, a novel metal-free photocatalytic system is reported that enables intramolecular hydroarylation of unactivated alkenes via a proton transfer shuttle using TFA, providing a concise access to the formation of pyrroloquinazolinone and pyridyquinazolinone products in moderate to good yields. Mechanistic studies revealed that the protonated quinazolinone is the key radical precursor mediating the intramolecular cyclization reaction.

Divergent total synthesis of sesquiterpene (hydro)quinone meroterpenoids dysideanones A and E–G

The first total synthesis of marine sesquiterpene (hydro)quinone meroterpenoids dysideanones A and E–G (1 and 4–6) has been accomplished in an enantioselective and divergent way. The sesquiterpene fragment and the aromatic moiety were efficiently connected via a site-selective and diastereoselective intermolecular alkylation of Wieland–Miescher ketone derivative 9 and benzyl bromide 10. The core 6/6/6/6-fused backbone of dysideanones was efficiently constructed through an intramolecular radical cyclization reaction. Dysideanone G (6) was easily prepared on a gram-scale and dysideanones A, E, and F (1, 4, and 5) were divergently transformed from dysideanone G (6) in one or two steps

Synthesizing Silyl Arylsulfonyl hydrazones as Silyldiazomethane Precursors and Their Use in Rhodium‐catalyzed Reactions

A method for synthesizing silyl arylsulfonyl hydrazones as silyldiazomethane precursors has been developed. Although silyldiazomethanes are an important class of diazo compounds, their use in intramolecular cyclization reactions has not been fully explored despite the rich chemistry of diazo compounds, particularly metal carbenoid chemistry. The fundamental challenge underlying the absence of such studies is the lack of a method for synthesizing silyldiazomethanes with functional groups that can react with metal carbenoids. The method reported here provides access to variety of silyl arylsulfonyl hydrazones with functional groups such as ethers, carbamates, and alkynes, which can serve as reaction sites for metal carbenoids. A one‐pot hydrazone formation using unstable formylsilane formed in situ is key to a successful synthesis. The use of 2,4,6‐trimethylbenzenesulfonohydrazide contributed toward achieving broad generality in hydrazone formation. The synthetic potential of this method was demonstrated through the generation of silyldiazomethane and its transformation to several silacycles.

Formation mechanism of polycyclic aromatic hydrocarbons in grilled beef and the mitigative effect of flavonoids

AbstractPolycyclic aromatic hydrocarbons (PAHs) are found in many common foods and increase the risk of cancer in humans. This study systematically screened the components that may be related to the formation of PAHs by an excessive addition of 19 amino acids and glucose in the beef patties. Phenylalanine and glucose exhibited the potential as promoters of PAHs, while lysine, aspartic acid, glutamic acid, valine, and methionine exhibited excellent potential as inhibitors of PAHs. Subsequently, a chemical model containing phenylalanine and glucose was established to confirm their roles as precursors of PAHs. The formation mechanism of PAHs showed that naphthalene was first formed as a basic structure, and then, PAHs with more rings were further formed through substitution, addition reactions, or intramolecular cyclization reactions. The mitigative effects of four flavonoids on total PAH contents were in the order: kaempferol > naringenin (better for individual PAH) > myricetin > quercetin (contradictory), which suggested that the antioxidant ability or radical scavenging capacity of flavonoids may be one of the pathways for PAH inhibition.

Iron‐catalyzed intermolecular and intramolecular cyclization reactions of N‐heterocycles

AbstractN‐Heterocyclic compounds have been appealing pharmacophores in their use as drug production substrates. In this review paper, the cyclization of N‐heterocycles, using iron as a catalyst, and their mechanistic pathways have been highlighted and presented comprehensively. This paper will provide researchers with in‐depth knowledge of their approach to synthesis by employing a greener way rather than a conventional one. The present review firmly establishes that iron catalysts by their innate ability and inherent potential to acquire the four oxidation states coupled with their easy accessibility, inexpensive, and environment‐friendly nature have remained the mainstay in chemistry as the evergreen catalyst in the domain of organic synthesis. This review paper extensively explores iron‐catalyzed cyclization of N‐heterocycles, elucidating mechanistic pathways and emphasizing greener synthesis methods. Iron's versatility, accessibility, and eco‐friendliness solidify its position as a cornerstone in organic synthesis.

Copper-Catalyzed Domino-Double Annulation of o-Aminobenzamides with 2-Iodoisothiocyanates for the Synthesis of 12H-Benzo[4,5]thiazolo[2,3-b]quinazolin-12-ones.

A facile and efficient copper-catalyzed domino-double annulation strategy was developed from easily accessible o-aminobenzamides and 2-iodoisothiocyanates, which affords a direct pathway for the synthesis of tetracyclic fused 12H-benzo[4,5]thiazolo[2,3-b]quinazolin-12-ones in moderate to good yields without the addition of ligands, bases, and external oxidants. The reaction involves a C-N bond cleavage and the formation of a C-N/C-S bond in one step with the advantages of using an inexpensive copper catalyst and easy operation. Mechanistic studies suggest that this transformation proceeds via intermolecular condensation of o-aminobenzamides with 2-iodoisothiocyanates, followed by an intramolecular Ullmann-type cross-coupling cyclization reaction.

A Simple and Efficient Approach for the Synthesis of Aryl-3-(trifluoromethyl)-1H-1,2,4-triazol-5(4H)-one Derivatives

AbstractIn this work, a series of 4-aryl-3-(trifluoromethyl)-1H-1,2,4-triazol-5(4H)-one derivatives is synthesized through nucleophilic intramolecular cyclization reactions of ethyl 2-(2,2,2-trifluoro-1-(arylimino)ethyl)hydrazine-1-carboxylate intermediates, which are themselves prepared in high yields via reactions of ethyl chloroformate and N-aryl-2,2,2-trifluoroacetimidoyl chloride derivatives. Some of the merits of the reported procedure are an operationally simple and concise method, the ready availability of starting materials, excellent product yields, no formation of harmful by-products and easy purification of the products.

Recent Advances in Synthetic Routes for Biologically Active Tetrahydroquinoxalines and Derivatives: A Comprehensive Review

Abstract: Tetrahydroquinoxalines are found in many biologically and pharmacologically active small molecules. In the past two decades, significant progress has been made in the development of novel synthetic routes for the preparation of biologically active tetrahydroquinoxalines and their derivatives. This synthetic review aims to provide a comprehensive overview of the advancements in the field of various synthetic strategies and methodologies employed for the synthesis of tetrahydroquinoxaline scaffolds during this period. The review emphasizes the diverse synthetic approaches employed, including cycloaddition reactions, condensation reactions, intramolecular cyclization reactions, ring expansion reactions, hydrogenation reactions, and other miscellaneous methods.

Defluorination of perfluorooctanoic acid and perfluorooctane sulfonic acid by heterogeneous catalytic system of Fe-Al2O3/O3: Synergistic oxidation effects and defluorination mechanism

In this study, catalytic ozonation by Fe-Al2O3 was used to investigate the defluorination of PFOA and PFOS, assessing the effects of different experimental conditions on the defluorination efficiency of the system. The oxidation mechanism of the Fe-Al2O3/O3 system and the specific degradation and defluorination mechanisms for PFOA and PFOS were determined. Results showed that compared to the single O3 system, the defluorination rates of PFOA and PFOS increased by 2.32- and 5.92-fold using the Fe-Al2O3/O3 system under optimal experimental conditions. Mechanistic analysis indicated that in Fe-Al2O3, the variable valence iron (Fe) and functional groups containing C and O served as important reaction sites during the catalytic process. The co-existence of 1O2, OH, O2− and high-valence Fe(IV) constituted a synergistic oxidation system consisting of free radicals and non-radicals, promoting the degradation and defluorination of PFOA and PFOS. DFT theoretical calculations and the analysis of intermediate degradation products suggested that the degradation pathways of PFOA and PFOS involved Kolbe decarboxylation, desulfonation, alcoholization and intramolecular cyclization reactions. The degradation and defluorination pathways of PFOA and PFOS consisted of the stepwise removal of -CF2-, with PFOS exhibiting a higher defluorination rate than PFOA due to its susceptibility to electrophilic attack. This study provides a theoretical basis for the development of heterogeneous catalytic ozonation systems for PFOA and PFOS treatment.

Mechanistic studies of HF/BF3-catalyzed anthracene polymerization to prepare mesophase pitch.

The mesophase pitch prepared by acid catalytic method typically had the advantages of low softening point and high solubility. To fully understand the mechanism of acid-catalyzed reactions and gain a deeper understanding of the microstructure of mesophase pitch, this article studied the mechanism of hydrofluoride/boron trifluoride (HF/BF3)-catalyzed anthracene using molecular simulation methods. The results showed that there might be two types of carbocations present in the system: classical and non-classical carbocations, and five reactions might occur, protonation reaction, chain elongation reaction, intramolecular cyclization reaction, deprotonation reaction, and dehydrogenation reaction. Classical carbocations acted as reactive intermediates in the chain elongation reaction and intramolecular cyclization reaction. When anthracene occurred chain elongation reactions with carbocations to form polymers, the generation of the tetramer required lager energy barriers than that of the dimer and trimer. The stiffness and flatness of molecules could be increased via intramolecular cyclization reactions. The polymers of anthracene might also occurred dehydrogenation reactions when the non-classical carbocations played the role of reactive intermediates. The dehydrogenation reactions required large energy barriers, which might be the reason for the product having a high aliphatic hydrogen content. The Materials Studio (MS) 2020 software was used to complete the simulation. The atomic charge distribution calculation and the structure optimization of molecules were carried out using the B3LYP functional and DNP basis. The DFT-D (TS) dispersion corrections were added to calculate the dispersion interaction between aromatic molecules. The complete LST/QST method was used to search the transition states and calculate the reaction energy barrier.

Relationship between PAH4 formation and thermal reaction products in model lipids and possible pathways of PAHs formation

Lipids are closely related to the generation of PAHs during food thermal processing. During heating, lipids mainly triglycerides undergo hydrolysis, oxidation and decomposition. The relationship between the various products and the formation of PAHs is still unclear. This paper investigated the effect of different lipid standards on PAH4 production, and explored their thermal stability and reaction products to delve into nature of the differences in PAH4 production. Fatty acids were more prone to generate PAH4 than glycerides. The higher the degree of esterification of glycerides, the higher its thermal stability and the lower the content of PAH4 generated, implying that hydrolysis of glycerides promoted the generation of PAH4. In addition, there was a positive correlation between unsaturation in lipids and the PAH4 production. After heat treatment, hydroperoxides, unsaturated fatty alcohols and aldehydes, alkenes and aromatic substances were abundant in oleic acid and linoleic acid which produced the most PAH4. Thermal decomposition of lipid hydroperoxides was the pathway for the generation of conjugated hydrocarbon radicals, alcohols, aldehydes, and alkenes. The intramolecular cyclization and Diels-Alder reaction acted as ring-forming reactions, with consequent dehydrogenation, decarboxylation, side-chain breaks and radical reorganization, ultimately facilitating the amplification of the aromatic rings and the formation of PAHs.

Palladium-catalyzed cyclization/carbonylation of iodoarene-tethered propargyl ethers with nitroarenes for the synthesis of acetamides-functionalized benzofurans

A general and efficient protocol based on palladium-catalyzed intramolecular cyclization and reductive aminocarbonylation reaction for the synthesis of acetamide-functionalized benzofurans has been explored. The reaction using iodoarene-tethered propargyl ethers and nitroarenes as the starting materials. This reaction features the formation of structure defined benzofurans with acetamides as attractive functional groups in a single step operation. By using Mo(CO)6 as both CO source and reductant, a variety of acetamides-functionalized benzofurans were obtained in moderate to good yields with good functional group compatibility.

Reaction Pathways in Esters and Carbonates.

This review reports on the competition/collaboration among intertwined base-catalyzed acyl cleavage bimolecular mechanism (BAc2)/base-catalyzed alkyl cleavage bimolecular mechanism (BAl2) or the related acid catalyzed mechanisms AAc2/AAl2 and AAl1 concerning Carbonates chemistry also in comparison with Esters reactivity. A consistent analysis of the experimental data so far available in the literature led to proposing a Model outlining the differences in energy profiles among the above-mentioned reaction mechanisms. The reactions involving Carbonates are so tightly interconnected that the formation of the final product is driven by a precise not interfering sequence of BAc2-BAl2 (or AAl2-AAc2) mechanisms. When entropic effect (in cyclizations) or an anchimneric effect (mustard carbonates, isosorbide methylation) are involved, the difference in Gibbs activation energy is reduced allowing chemical transformations that would normally require higher temperatures. In these cases (intramolecular alkylation, cyclisation reaction, and alkylation by mustard carbonates) only a catalytic amount of base is required as the leaving group CH3OCOO- decomposes restoring the base. As Green Chemistry is concerned, syntheses with much lower environmental impact are achieved with Carbonates when compared with the corresponding ones involving Chlorine chemistry.

Light-Driven Two-Step Preparation of 4-Chromanone Fused to Estrone Derivatives.

A protocol involving the irradiation of some 3-(2-alkenyl)estrone and 3-(2-alkenyl)-17-norestrone derivatives under a nitrogen atmosphere in organic solvents (both hexane and MeOH) followed by base-mediated intramolecular oxa-Michael cyclization reaction was investigated under steady-state conditions. The solvent effect and nature of the acyl group on the preparative photoreaction were studied and the multiplicity of the excited state was also demonstrated. The ortho-regioisomers were obtained in modest to good yields. Intramolecular based-mediate cyclization reaction of these synthons led to the formation of a set of novel substituted 4-chromanone moieties fused to estrone (and 17-norestrone) in good yields. This two-step sequential procedure involving a photochemical/intramolecular thermal cyclization strategy will be useful for the preparation of wide heterocyclic-fused-steroid compounds.

Pd-Catalyzed Regioselective (Markovnikov) Addition of Aryl Boronic Acids to Terminal Alkynes of 1,3-Dicarbonyl Compounds and Cyclization/Debenzoylation of Olefinic Dicarbonyl: Access to Arylated Pyran and (E)-4-Methylene-1,6-diphenylhex-5-en-1-one.

This Letter outlines palladium-catalyzed regioselective (Markovnikov's) addition of aryl boronic acids to propargyl 1,3-dicarbonyl alkyne to accomplish olefinic/diene 1,3-dicarbonyl compounds without the need for water workup. This methodology showcases remarkable performance with wide-ranging substrate diversity, achieving high yields while employing merely 3 mol % [Pd] alongside a mild KOAc base. Moreover, the utility of dicarbonyl olefins is exemplified through their application in intramolecular cyclization and debenzoylation reactions to access valuable trisubstituted pyran building blocks and (E)-4-methylene-1,6-diphenylhex-5-en-1-one synthesis.

PhIO‐Mediated Cascade Reactions of Activated Acetylamides and Cyclic Amidines: Access to Polysubstituted Imidazolidin‐2‐ones

AbstractA facile and efficient synthesis of polysubstituted imidazolidin‐2‐ones has been developed via an oxidative cyclization reaction of activated acetyl amides and cyclic amidines mediated by iodosobenzene (PhIO). A mechanism is proposed for this transformation, which involves sequential intermolecular addition, Hofmann‐type rearrangement and intramolecular cyclization reactions. The novel protocol features readily available starting materials, mild reaction conditions, simple execution, metal‐free oxidative cyclization, and one‐pot procedure.