Metal-free Cyclization Research Articles

K2CO3-Catalyzed Dual C-C-Coupled Cyclization to 3-Amino-4-benzoylbiphenyls and In Situ I2-Catalyzed C-N Bond Forming Annulation: A Metal-Free Synthesis of Arylacridones.

Unprecedented metal-free cyclization catalysis reactions are developed in a highly regioselective fashion to synthesize 3-amino-4-benzoyl biphenyls and arylacridones with high atom economy. Catalytic K2CO3 is utilized as the only reagent for the unusual rapid dual C-C-coupled cyclization between β-keto enamines and cinnamaldehydes to furnish the functionalized biphenyls. Its C(sp2)-H functionalized C-N bond-forming cyclization was performed in situ using molecular I2 as a catalyst to furnish valuable arylacridones. Plausible mechanisms for the new cyclization reactions are predicted by conducting various control experiments and ESI-MS analyses.

Modular Synthesis of Tetrasubstituted Pyrroles via an Annulative Migration Reaction of Allenyl Ketones and p-Toluenesulfonylmethyl Isocyanide.

The metal-free cyclization of allenyl ketones and p-toluenesulfonylmethyl isocyanide (TosMIC), promoted by Cs2CO3, provides a convenient access to tetrasubstituted pyrroles in which an acyl group undergoes 1,2-migration. This tandem Michael addition/annulative migration synthetic strategy is general and high-yielding for various substituted allenyl ketones. Moreover, a phosphoryl or ester moiety is also a suitable functionality to enable such migration.

Iodine-Promoted Metal-Free Cyclization and O/S Exchange of Acrylamides with Thiuram: One-Step Synthesis of Quinolino-2-thiones.

A one-step cyclization and O/S exchange reaction of readily available acrylamides in the presence of iodine and thiuram has been developed. The reaction provides an efficient approach for the synthesis of highly important heterocycle quinolino-2-thiones with diverse substitution patterns.

Synthesis and Biological Activities of Pyrazino[1,2-a]indole and Pyrazino[1,2-a]indol-1-one Derivatives.

This review concerns the synthesis and biological activities of pyrazino[1,2-a]indoles and pyrazino[1,2-a]indol-1-ones reported since 1997 and the discovery of biological activity of pyrazinoindole derivatives. In the first part, we first presented the synthetic routes that have been reported from a methodological point of view to access the pyrazinoindole unit according to cyclization reactions using or not using metal catalysts. Then, syntheses and neuropsychiatric, auto-immune, anti-infectious and anti-cancer properties of pyrazinoindoles were detailed. In the second part, we first reported the main accesses to pyrazinoindol-1-one substrates according to Michael reactions, metal-catalyzed and metal-free cyclization reactions. The syntheses and anti-cancer, anti-infectious, anti-allergenic and neuropsychiatric properties of pyrazinoindolones were next described and discussed.

Versatile Direct Cyclization Constructs Spiro-acridan Derivatives for Highly Efficient TADF emitters.

Spiro-acridan (SpA) derivatives possess a great potential in preparing efficient thermally activated delayed fluorescent (TADF) emitters. However, the conventional synthetic routes are cost-expensive and time-consuming. The development of a simple procedure to synthesize SpAs is still in urgent pursuing appreciated by academic and industrial communities. In this contribution, we present a feasible acid-catalyzed solvent-free metal-free cyclization between diarylamines and ketones to construct SpAs. The as-constructed moieties provide a wide possibility to assemble efficient TADF emitters. As an example, D2T-TR with high photoluminescent quantum yield and proper TADF character is applied in organic light emitting diodes (OLEDs) which achieves a maximum external quantum efficiency (EQE) of 27.1 %. This work shows us a bright inspiration on developing excellent organic optoelectronic materials and an effective tool to realize it.

Mechanistic details of metal-free cyclization reaction of organophosphorus oxide with alkynes mediated by 2,6-lutidine and Tf2 O.

Theoretical investigations have elucidated the mechanism of metal-free electrophilic phosphinative cyclization of alkynes reaction reported by Miura and coworkers. Two competitive mechanisms I and II were explored without or with 2,6-lutidine. Both of I and II involve transformation of P(V) to P(III), electrophilic addition, ring opening and cyclization/cyclization, hydrogen-transfer, and oxidation. The rate-determining step of mechanism I and competitive less-step II is electrophilic [2 + 1] cycloaddition and electrophilic addition via single CP bond formation with activation barrier of 13.5 and 10.6 kcal/mol, respectively. Our calculation results suggested that the cumulative effect of the isomer of 2,6-lutidine and Tf2 O as well as TfO- affects the title reaction to some extent, and simultaneously activates key reaction sites and reverses the polarities of them via the formation of abundant noncovalent interactions to decrease activation barriers of TSs. In addition, the effects of two series substituents on reactivity of phosphine oxide were investigated. Therefore, our study will serve as useful guidance for more efficient metal-free synthesis of organophosphorus compounds mediated by pyridine reagents.

BF3·OEt2-mediated cyclization of β,γ-unsaturated oximes and hydrazones with N-(arylthio/arylseleno)succinimides: an efficient approach to synthesize isoxazoles or dihydropyrazoles.

A highly efficient BF3·OEt2-mediated cyclization of β,γ-unsaturated oximes and tosylhydrazones with N-(arylthio/arylseleno)succinimides has been established for the construction of N-heterocycles in a one-step manner. This metal-free cyclization provides direct access to isoxazoles and dihydropyrazoles in good to excellent yields at room temperature. The mechanistic experiments support the formation of a cationic species PhS+ which plays a critical role in this cyclization process.

A Simple Metal-Free Cyclization for the Synthesis of 4-Methylene-3-Substituted Quinazolinone and Quinazolinthione Derivatives: Experiment and Theory.

A new series of 3-substituted 4-methylene-quinazolinthiones and 4-methylene-quinazolinones were synthesized in moderate to excellent yield through a simple reaction of 2-aminoacetophenones with isocyanates or isothiocyanates. The reaction shows good tolerance of many important functional groups in the presence of air and water under metal-free conditions. Only water is produced as a coproduct, rendering this “green” methodology a highly versatile and eco-friendly alternative to the existing methods for the construction of the quinazolinone/quinazolinthione framework. We have interpreted the reaction mechanism by use of quantum chemical calculations on the basis of state-of-the-art computational methods SMD-B3LYP-D3(BJ)/BS1//B3LYP/BS1.

Metal-free cyclization of unsaturated hydrazones for the divergent assembly of pyrazolones and pyrazolines.

An oxidative cyclization of β,γ-unsaturated hydrazones for the divergent assembly of pyrazolones and pyrazolines under metal-free conditions is presented. This divergent synthetic strategy was achieved by controlling the reaction atmosphere. A number of pyrazolines were obtained via 5-exo-trig cyclization when the reaction was performed under N2. Whereas when the reaction was conducted under O2, diverse functionalized pyrazolones were achieved via oxidative cleavage of the C[double bond, length as m-dash]C double bond.

Metal-Free Cyclization of ortho-Nitroaryl Ynamides and Ynamines towards Spiropseudoindoxyls.

An efficient metal-free cascade reaction between 1-dibromovinyl-2-nitro-substituted arenes and secondary amines results in the formation of polycyclic pseudoindoxyls in a single step. The reaction mechanism leading to these fused ring systems was investigated, and is believed to involve the initial formation of nitroarylated ynamines/ynamides. These intermediates cycloisomerize towards N-alkenyl-tethered 2-aminoisatogens via a carbene intermediate as demonstrated by QTAIM (quantum theory of atoms in molecules) and ELF (electron localization function) analysis. A subsequent intramolecular dipolar cycloaddition afforded the title compounds.

Preparation of oxazolines and oxazolesviaa PhI(OAc)2-promoted cyclization ofN-propargylamides

A metal-free cyclization of N-propargylamides for the synthesis of various oxazolines and oxazoles via a 5-exo-dig process is presented. Using (diacetoxyiodo)benzene (PIDA) as a reaction promoter and lithium iodide (LiI) as an iodine source, intramolecular iodooxygenation of N-propargylamides proceeded readily, leading to the corresponding (E)-5-iodomethylene-2-oxazolines in good to excellent isolated yields. In addition, using the PhI(OAc)2/LiI system, N-propargylamides can be converted to the corresponding oxazole-5-carbaldehydes in the presence of oxygen under visible light irradiation. The resulting products can be further converted into various oxazoline and oxazole derivatives after simple derivatizations, and this method ultimately offers an efficient route to a variety of biologically active structures.

Synthesis and Properties of Aza-ullazines.

A range of aza-ullazines, which represent a new heterocyclic core structure, were synthesized through a scalable four-step reaction, including a Sonogashira reaction and metal-free cyclization promoted by p-toluenesulfonic acid. The optical and electrochemical properties of selected derivatives were investigated, they were found to have similar absorption and emission spectra but a higher oxidation potential than the parent ullazine core.

Synthesis of Substituted 1,2,3-Triazoles via Metal-Free Click Cycloaddition Reactions and Alternative Cyclization Methods

Click chemistry is one of the most efficient and widely used methodologies for selective C–N bond forming reactions, encompassing the synthesis of 1,2,3-triazoles, and it has been continued to be of great interest in synthetic and medicinal chemistry since its discovery. Diversely substituted 1,2,3-triazoles synthesized by classical Huisgen 1,3-dipolar cycloaddition of azides with alkynes have a broad spectrum of biological properties and they are widely accessed using transition-metal catalysts, such as copper- and ruthenium-catalyzed azide-alkyne cycloaddition [MAAC] reactions. In contrast, the development of organocatalyzed click chemistry has recently emerged as one of the most important alternative strategies to transition-metal-mediated reactions, because of its sustainability, environmentally benign processes and, moreover the absence of metals toxic to biological systems including living cells and biomolecules such as DNA. The focus of this review is on the recent advances in the organocatalytic click chemistry of enamine and enolate-mediated [3+2] cycloadditions and alternative metal-free cyclization reactions for the preparation of diversely functionalized 1,2,3-triazoles. The scope and limitations of these methods and also their applications for the synthesis of bioactive hybrid molecules are discussed. 1 Introduction 2 Enamine-Mediated Triazole Synthesis 3 Enolate-Mediated Triazole Synthesis 4 Alternative Metal-Free Triazole Synthesis 5 Applications to the Synthesis of Bioactive Compounds 6 Summary

The intramolecular 5-exo, 7-endo-dig transition metal-free cyclization sequence of (2-alkynylphenyl) benzyl ethers: synthesis of seven-membered fused benzo[b]furans

We present the results of the intramolecular transition metal-free cyclization of (2-alkynylphenyl) benzyl ethers promoted by sodium tert-butoxide.

Metal-free oxidative functionalization of a C(sp(3))-H bond adjacent to nitrogen and intramolecular aromatic cyclization for the preparation of 6-amidophenanthridines.

A metal-free cyclization reaction of 2-isocyanobiphenyls with amide derivatives by using tert-butyl peroxybenzoate (TBPB) as oxidant was developed, which provided an access to pharmacologically interesting 6-amidophenanthridine compounds. The reactions proceeded through a sequence of functionalization of the C(sp(3))-H bond adjacent to the nitrogen atom and intramolecular radical aromatic cyclization with good chemistry yields.

A novel one-pot method for the synthesis of substituted furopyridines: iodine-mediated oxidation of enaminones by tandem metal-free cyclization

A novel iodine-mediated oxidative tandem cyclization reaction of simple enaminones has been developed for the synthesis of substituted furopyridines through C-C/C-N/C-O bond formation in a one-pot procedure. Substituted furopyridines are obtained in moderate to good yield. In addition, I- and Br-substituted furopyridines have been successfully produced by the electrophilic substitution of N-iodo- or N-bromosuccinimide.

Facile synthesis of benzoindoles and naphthofurans through carbonaceous material-catalyzed cyclization of naphthylamines/naphthols with nitroolefins in water.

A facile and efficient approach has been established for the synthesis of benzoindole and naphthofuran derivatives via the metal-free cyclization reaction of nitroolefins with naphthylamines/naphthols. Various substituted benzoindoles and naphthofurans are obtained in good to excellent yields. Moreover, the ability to recycle the carbonaceous material makes this method quite cost-effective and environmentally benign compared to traditional acid-catalyzed methods. Theoretical studies indicated that the reaction between naphthylamine and nitroolefin catalyzed by this solid acid was thermodynamically controlled at 60 °C, resulting in the formation of the benzoindoles.

Cyclization and N-Iodosuccinimide-Induced Electrophilic Iodocyclization of 3-Aza-1,5-enynes To Synthesize 1,2-Dihydropyridines and 3-Iodo-1,2-dihydropyridines

Metal-free cyclization and N-iodosuccinimide-induced electrophilic iodocyclization of readily available 3-aza-1,5-enynes have been developed. The reactions selectively give 1,2-dihydropyridines and 3-iodo-1,2-dihydropyridines involving an aza-Claisen rearrangement and a 6π-electrocyclization step. Furthermore, the reaction could be carried out in 10 g scale for the synthesis of 1,2-dihydropyridines.

ChemInform Abstract: Hypervalent Iodine Mediated Oxidative Cyclization of o‐Hydroxystilbenes into Benzo‐ and Naphthofurans.

A new and convenient metal-free cyclization of ortho-hydroxystilbenes into 2-arylbenzofurans and 2-arylnaphthofurans mediated by hypervalent iodine reagents is described. The cyclization products are isolated in good to excellent yields using stoichiometric (diacetoxyiodo)benzene in acetonitrile.

Hypervalent Iodine Mediated Oxidative Cyclization of o-Hydroxystilbenes into Benzo- and Naphthofurans

A new and convenient metal-free cyclization of ortho-hydroxystilbenes into 2-arylbenzofurans and 2-arylnaphthofurans mediated by hypervalent iodine reagents is described. The cyclization products are isolated in good to excellent yields using stoichiometric (diacetoxyiodo)benzene in acetonitrile.