Benzannulation Reaction Research Articles

Domino Reaction of 2,4-Diyn-1-ols with 1,3-Dicarbonyl Compounds: Direct Access to Aryl/Heteroaryl-Fused Benzofurans and Indoles.

A domino propargylation/furanylation (intramolecular exo-dig-cyclization)/benzannulation reaction of 2,4-diyn-1-ols with 1,3-dicarbonyl compounds has been developed for the first time. This provides a novel and effective method for the preparation of aryl/heteroaryl-fused benzofurans from easily accessible starting materials in a single step. The methodology was extended to pyrrolyl-benzannulation to obtain aryl/heteroaryl-fused indoles. Further, application of this approach in the synthesis of eustifoline D and dictyodendrin structural frameworks has been demonstrated.

N‐Heterocyclic Carbene Catalyzed Benzannulations: Mechanism and Synthetic Utility

AbstractAromatic compounds are ubiquitous in pharmaceutical agents and other functional materials. Therefore, synthetic methods to construct highly functionalized aromatic frameworks have attracted considerable attention, especially when utilizing acyclic precursors instead of pre‐existing benzenoid cores. A plethora of methods exist in the literature for the construction of substituted aromatic products by using transition metal catalysis and base‐promoted benzannulation reactions starting from acyclic precursors. In recent years, organocatalytic approaches such as N‐heterocyclic carbene catalysis have emerged as effective tools for the efficient and regioselective construction of highly functionalized aryl rings under metal‐free and mild reaction conditions. The fundamental objective of this minireview is to highlight the synthetic potential of NHC‐catalyzed benzannulations for the generation of aromatic rings with complex substitution patterns and to discuss these reactions from the perspective of their mechanistic design.

De Novo Construction of Substituted Terephthalates via Phosphine Catalyzed Domino Benzannulation Reactions

AbstractThe robustness of phosphine catalysis enabling the domino benzannulation reactions of allenoates with enamines is described. A broad array of substituted terephthalates were delivered under simple and practical reaction conditions. Furthermore, the reaction could be carried out on a gram scale with higher yield, and various conversions of the terephthalate products demonstrate the versatility of this transformation.magnified image

Selective synthesis of 1-halonaphthalenes by copper-catalyzed benzannulation

Abstract The synthesis of 1-halonaphthalenes by the Cu-catalyzed benzannulation reaction of 2-(phenylethynyl)benzaldehyde and alkynes in the presence of the halogen reagents such as NBS, NCS, and NIS, was developed. This protocol afforded various type of 1-halonaphthalenes in moderate to excellent yields and the cross coupling reactions of 1-bromo-2-phenylnaphthalene prepared by this method with various reagents occurred to give the corresponding 1,2-disubstituted naphthalenes.

Direct Assembly of Polysubstituted Naphthalenes via a Tandem Reaction of Benzynes and α-Cyano-β-methylenones.

A mild and transition-metal-free benzannulation reaction for the construction of the naphthalene skeleton has been described. Benzynes react with α-cyano-β-alkylenones through a tandem nucleophilic addition/cyclization/aromatization process to afford polysubstituted naphthalenes in 50-94% yields.

Synthesis of Coumarins via [4+2] Cyclization of Siloxy Alkynes and Salicylaldehydes

AbstractA new approach for the synthesis of coumarins from siloxy alkynes and salicylaldehydes is disclosed. Unlike the previous benzannulation reactions of siloxy alkynes that all proceed by electron-inversed Diels–Alder mechanism, this process represents a new [4+2] cyclization. In the presence of the superior HNTf2 catalyst, a wide range of coumarins were efficiently synthesized. This process was also extended to the synthesis of 2-quinolones. The polarized electron-rich triple bond might react sequentially with the aldehyde and hydroxy group by polarity switching in the stepwise formation of the C–C and C–O bonds. Control experiments provided insights into the mechanistic understanding.

Recent Advances in Organocatalyst‐Mediated Benzannulation Reactions

AbstractAromatic compounds are omnipresent in organic chemistry, which are the broadest skeletons of bioactive molecules, medicines, and materials. Due to their importance, conventional methods to assemble aromatic rings have attracted considerable attention. The direct formation of benzene cores from readily available acyclic precursors offers a highly versatile and superior approach to prepare both small organic molecules and sophisticated natural products. Recently, organocatalyst‐mediated annulation reaction, including phosphine‐, tertiary amine‐, secondary amine‐, primary amine‐, and NHC‐mediated benzannulation reactions, is considered as an efficient method to access multi‐substituted arenes. In this review, we will emphasize the selected examples of organocatalyst‐mediated benzannulation reactions of available acyclic precursors for the construction of diverse aromatics.magnified image

Selective Syntheses of Benzo[b]carbazoles and C3‐Substituted Indoles via Tunable Catalytic Annulations of β‐Alkynyl Ketones with Indoles

AbstractTunable catalytic annulation reactions of β alkynyl ketones with indoles have been developed, enabling multiple chemical bond‐forming events to selectively access skeletally diverse indole‐containing heterocycles with generally good yields. Silver‐catalyzed intermolecular benzannulation reaction of β‐alkynyl ketones with indoles afforded tetracyclic benzo[b]carbazoles whereas isochromen‐1‐yl‐substituted indoles could be obtained using the same silver catalysis by lowering the reaction temperature (0 °C or rt). Interestingly, using Sc(OTf)3 and AgOTf as a combined catalytic system led to the formation of C3‐naphthylated indoles via intramolecular benzannulation reaction.magnified image

Copper-Catalyzed Three-Component Formal [3 + 1 + 2] Benzannulation for Carbazole and Indole Synthesis.

Three-component formal [3 + 1 + 2] benzannulation reactions of indole-3-carbaldehydes or 1-methyl-pyrrole-2-carbaldehydes with two different molecules of saturated ketones have been successfully developed under Cu-catalyzed and 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-mediated conditions. Various unsymmetrically substituted carbazoles and indoles were obtained up to 95% yield. Furthermore, the resulting products exhibit unusual aggregation-induced emission (AIE) properties in the solid state. This method features high atom-economy, cheap catalysts and oxidants, wide substrate scope, and saturated ketones as one-carbon and two-carbon sources, thus providing an efficient approach to polycyclic carbazole and indole compounds.

The Dötz Benzannulation Reaction: A Booming Methodology for Natural Product Synthesis

AbstractSince its finding in 1975, the Dötz benzannulation reaction has attracted a great attention of the scientific community as it permits the regio‐controlled construction of functionalised aromatic frameworks from acyclic precursors. In recent years, this beautifully simple yet much powerful technique for the formation of C−C bonds has opened‐up new possibilities in modern synthetic organic chemistry. In this Review, we report the developments in natural products synthesis by employing the Dötz benzannulation as a key transformation. Although, a flow of publications have witnessed a constant progress in this wonderful area of research, but to our best knowledge this is the first review which purely focuses on the applications of the Dötz benzannulation reaction in natural product synthesis. We are assured that this review will act as a promoter in amplifying the applications of the Dötz benzannulation in the domain of synthetic organic chemistry.

Palladium-Catalyzed Cascade Decarboxylative Amination/6-endo-dig Benzannulation of o-Alkynylarylketones with N-Hydroxyamides To Access Diverse 1-Naphthylamine Derivatives.

An efficient and practical one-pot strategy to produce highly substituted 1-naphthylamines via sequential palladium-catalyzed decarboxylative amination/intramolecular 6-endo-dig benzannulation reactions has been described. In this reaction, a broad range of electron-rich, electron-neutral, and electron-deficient o-alkynylarylketones react well with N-hydroxyl aryl/alkylamides to give a diversity of 1-naphthylamines in good to excellent yields under mild reaction conditions. The gram-scale synthesis, with benefits such as undiminished product yield and easy transformation, illustrated the practicality of this method.

Regioselective synthesis of benzonitriles via amino-catalyzed [3+3] benzannulation reaction

A straightforward synthesis of benzonitriles is achieved via amino-catalyzed [3+3] benzannulation of α,β-unsaturated aldehydes and 4-arylsulfonyl-2-butenenitriles. Using pyrrolidine as an organocatalyst via iminium activation, a series of substituted benzonitriles were obtained in good to high yields in a regioselective manner. This reaction can proceed smoothly under mild reaction conditions and without the aid of any metals, additional oxidants, or strong bases, thus making this an efficient and environmentally friendly method to access benzonitriles.

Organic Transformations Using Electron-Deficient Boron Compounds

The molecular structures and chemical reactivity of boron compounds are characterized by the electron deficiency and low electronegativity of boron. Based on simple molecular design strategy taking advantage of the unique properties of boron, we have developed new chemical species and new organic transformations. This article describes our recent studies of (i) a two-coordinate boron cation (borinium ion) and (ii) a 9-borafluorene-mediated benzannulation reaction of alkyne derivatives. In the former, we successfully isolated a diarylborinium ion (Mes2B+), which had been considered impossible to be isolated as a stable species without introducing particular electron-donating groups to boron. We found several unique small-molecule activation reactions mediated by Mes2B+ such as C=O double bond cleavage of CO2. Moreover, we revealed that Mes2B+ serves as an excellent hole-doping reagent for carbon nanotube, graphene, and transition metal dichalcogenide. In the latter topic, we discovered a new efficient boron-mediated benzannulation reaction of alkyne derivatives, which enables the synthesis of a wide variety of extended π-conjugated molecules and polymers. The boron compounds used in these studies are simple but enable powerful organic transformations.

One-Pot Assembly of 3-Hydroxycarbazoles via Uninterrupted Propargylation/Hydroxylative Benzannulation Reactions.

A novel strategy for the synthesis of 3-hydroxycarbazoles involving the consecutive propargylation/palladium-catalyzed hydroxylative benzannulation of indole-2-carbonyls with propargylic alcohols has been exploited. This one-pot procedure leads to a wide range of substituted 3-hydroxycarbazoles in high yield with a broad substrate scope. The method was further extended to access furano-carbazole derivatives from dialkynols via tandem annulations.

Cooperative Palladium and Copper Catalysis: One‐pot Synthesis of Diamino‐Substituted Naphthalenes from Aryl Halides, 1,4‐Bis(trimethylsilyl)butadiyne and Amines

AbstractA one‐pot method for the preparation of diamino‐substituted naphthalene derivatives from easily available starting materials aryl halides, 1,4‐bis(trimethylsilyl)butadiyne and amines is developed. Two C−N bonds, three C−C bonds and one aromatic ring are formed in this domino process. This transformation is achieved by the cooperative catalysis of Pd(OAc)2, Cu(Xantphos)I and Cu(OTf)2. A possible double Sonogashira coupling/hydroamination/ benzannulation reaction route is proposed.

Alkyne benzannulations in the preparation of contorted nanographenes

Nanographenes are a popular area of research due to their promising properties for electronics. Over the last twenty years there has been a significant increase in interest in the development of contorted nanographenes. While many top-down techniques are employed in the synthesis of these planar nanographenes, the use of alkynes in bottom-up syntheses allows for easy functionalization and the development of contorted nanographenes. The syntheses of contorted nanographenes with a focus on utilizing alkynes is reviewed here.

Biaryl and atropisomeric biaryl aldehyde synthesis by one-step, metal-free benzannulation of aryl enals and propiolates

The metal-free benzannulation reactions of alkyl propiolates and aryl enals have been developed for biaryl and atropisomeric biaryl aldehyde synthesis.

Efficient Synthesis of Polyfunctionalized Benzenes in Water via Persulfate-promoted Benzannulation of α,β-Unsaturated Compounds and Alkynes.

Benzannulation reactions represent an effective protocol to transform acyclic building blocks into structurally varied benzene skeletons. Despite classical and recent approaches toward functionalized benzenes, in water metal-free methods remains a challenge and represents an opportunity to expand even more the set of tools used to synthesize polysubstituted benzene compounds. This protocol describes an operationally simple experimental setup to explore the benzannulation of α,β-unsaturated compounds and alkynes to afford unprecedented functionalized benzene rings in high yields. Ammonium persulfate is the reagent of choice and brings notable advantages as stability and easy handling. Moreover, the use of water as a solvent and the absence of metals impart more sustainability to the method. A modified workup procedure that avoids the use of drying agents also adds convenience to the protocol. The purification of the products is performed using only a plug of silica. The substrate scope is currently limited to terminal alkynes and α,β-unsaturated aliphatic compounds.

An Expeditious Benzannulation Reaction of Indol‐3‐yl‐but‐3‐yn‐2‐ols to Substituted 2‐Iodocarbazoles via Domino 5‐endo Spirocyclization/Selective Vinyl Shift and Aromatization

Regioselective benzannulation reaction of indol‐3‐yl‐but‐3‐yn‐2‐ols to functionaly embellished 2‐iodocarbazoles is described for the first time using iodine at room temperature in an open flask. This reaction proceeds through a cascade of 5‐endo spirocyclization, ring‐rearrangement through a vinyl shift, and aromatization in a short time. This protocol offers direct access to uncovered 2‐iodocarbazoles, with a broad substrate scope and good to moderate yields. Further, we have demonstrated the synthetic potential of these compounds using cross‐coupling reactions.

Four-Fold Alkyne Benzannulation: Synthesis, Properties, and Structure of Pyreno[a]pyrene-Based Helicene Hybrids.

The synthesis of pyreno[a]pyrene-based helicene hybrids was achieved in good yield via a four-fold alkyne benzannulation reaction that was promoted by Brønsted acid. The molecules are configurationally locked, allowing the enantiomers to be separated using chiral HPLC so that their photophysical and chiroptical properties, including circular dichroism and circularly polarized luminescence, could be studied.