Benzannulation Reaction Research Articles

A Regioselective Domino Benzannulation Route to Indeno[1,2-a]fluorene-7,12-diones

AbstractA base-promoted domino benzannulation reaction of 2,3-dibromoindenone with acyclic 1,3-dicarbonyls resulted in an efficient synthetic protocol for a series of novel polycyclic indeno[1,2-a]fluorenes. The reaction proceeds via the two sequential addition-elimination reactions of nucleophilic species generated from the 1,3-dicarbonyls under basic conditions, serendipitously leading to the benzannulation with two molecules of 2,3-dibromoindenone. The second addition-elimination occurs on the initially formed adduct of 1,3-dicarbonyl with 2,3-dibromoindenone, setting the stage for further intramolecular cyclization and aromatization. Interestingly, unsymmetrical 1,3-dicarbonyls furnished a single regioisomer. The origin of the regioselectivity and plausible mechanism is discussed.

Some New Aspects of Gold-Catalyzed Benzannulation Reaction

Introduction: The gold-catalyzed benzannulation reaction of oxo-alkynes with al-kenes or alkynes is one of the important and unique reactions in gold-catalyzed organic trans-formations. Methods: In this manuscript, many facets of this reaction have been discussed concerning reac-tivity and selectivity, along with a new self-benzannulation process. The scope of this chemistry was extended to construct a phenanthrene moiety. Results: In addition, a palladium-gold dual catalytic arylation of isobenzopyrylium salts using arene-diazonium salts as an aryl group source and a one-pot isoquinoline synthesis is reported for the first time. Conclusion: Moreover, a conductance measurement experiment was performed, which supports the formation of ionic species, most likely the isobenzopyrylium auric ate complex as an inter-mediate formed during the reaction process.

Ru(II)-Catalyzed Deoxygenative Formal [3 + 1 + 2] Benzannulation of Allyl Alcohols and Acetylenediesters via C-H Activation and Selective Carbon-Carbon Triple Bond Cleavage.

An unprecedented Ru(II)-catalyzed deoxygenative, site-selective formal [3 + 1 + 2] benzannulation reaction for the efficient synthesis of highly substituted benzene molecules is reported. This reaction between allyl alcohols and acetylenedicarboxylate esters proceeds via cascade C-H activation, consecutive double migratory insertion with alkynes, and cycloaromatization followed by an unusual specific C-C triple bond cleavage.

Regioselective Synthesis of Polysubstituted Carbazoles from Indoles and Simple 1,4‐Dicarbonyl Compounds

AbstractPolysubstituted carbazoles were efficiently synthesized through direct benzannulation reaction between 1,4‐dicarbonyl compounds and indoles with catalytic amount of inexpensive zirconium(IV) chloride. This transformation proved to be regioselective and furnishes 1,4‐disubstituted and 1,2,4‐trisubstituted carbazoles with yields ranging from 26% to 91% and broad substrate scope. Moreover, this protocol benefits from using readily accessible starting materials without the need of their pre‐functionalization. The synthetic utility of the products was exemplified by functionalization of an iodocarbazole by means of Suzuki‐Miyaura reactions and by the synthesis of a 3‐deaza‐derivative of the natural product canthin‐6‐one.

Co(III)-catalyzed regioselective benzannulation of substituted pyridones with 1,6-diynes via dual C-H bond activation.

A Co(III)-catalyzed site-selective C5 and C6 benzannulation of substituted pyridones with 1,6-diynes via dual C-H bond activation has been reported. The scope of the benzannulation reaction was examined with various substituted 2-pyridyl pyridones and 1,6-diynes. The combination of cuprous acetate and silver carbonate plays a crucial role in the success of the reaction. A plausible reaction mechanism was proposed and supported by deuterium labelling studies and radical trapping experiments.

Towards bioresource-based aggregation-induced emission luminogens from lignin β-O-4 motifs as renewable resources

One-pot synthesis of heterocyclic aromatics with good optical properties from phenolic β-O-4 lignin segments is of high importance to meet high value added biorefinery demands. However, executing this process remains a huge challenge due to the incompatible reaction conditions of the depolymerization of lignin β-O-4 segments containing γ-OH functionalities and bioresource-based aggregation-induced emission luminogens (BioAIEgens) formation with the desired properties. In this work, benzannulation reactions starting from lignin β-O-4 moieties with 3-alkenylated indoles catalyzed by vanadium-based complexes have been successfully developed, affording a wide range of functionalized carbazoles with up to 92% yield. Experiments and density functional theory calculations suggest that the reaction pathway involves the selective cleavage of double C-O bonds/Diels-Alder cycloaddition/dehydrogenative aromatization. Photophysical investigations show that these carbazole products represent a class of BioAIEgens with twisted intramolecular charge transfer. Distinctions of emission behavior were revealed based on unique acceptor-donor-acceptor-type molecular conformations as well as molecular packings. This work features lignin β-O-4 motifs with γ-OH functionalities as renewable substrates, without the need to apply external oxidant/reductant systems. Here, we show a concise and sustainable route to functional carbazoles with AIE properties, building a bridge between lignin and BioAIE materials.

The influence of proton-donor solvent on [4+2] benzannulation reaction of dienal with tertiary enaminone

The [4+2] benzannulation synthesis of benzaldehyde derivative containing an electron withdrawing group at the C3 position by using the dienal and tertiary enaminone is the practical method recently, which can only be carried out in protic organic solvent. Here, the quantum chemical calculation indicates that the solvent molecule plays the vital role of proton donor which can significantly decrease the activation energy and accordingly increase the reaction speed or trend. This study provides a novel understanding for the effect of solvent environment on reaction mechanism.

Living Suzuki-Miyaura Catalyst-Transfer Polymerization for Precision Synthesis of Length-Controlled Armchair Graphene Nanoribbons and Their Block Copolymers.

The bottom-up synthesis of graphene nanoribbons (GNRs) offers a promising approach for designing atomically precise GNRs with tuneable photophysical properties, but controlling their length remains a challenge. Herein, we report an efficient synthetic protocol for producing length-controlled armchair GNRs (AGNRs) through living Suzuki-Miyaura catalyst-transfer polymerization (SCTP) using RuPhos-Pd catalyst and mild graphitization methods. Initially, SCTP of a dialkynylphenylene monomer was optimized by modifying boronates and halide moieties on the monomers, affording poly(2,5-dialkynyl-p-phenylene) (PDAPP) with controlled molecular weight (Mn up to 29.8k) and narrow dispersity (Đ = 1.14-1.39) in excellent yield (>85%). Subsequently, we successfully obtained N = 5 AGNRs by employing a mild alkyne benzannulation reaction on the PDAPP precursor and confirmed their length retention by size-exclusion chromatography. In addition, photophysical characterization revealed that a molar absorptivity was directly proportional to the length of the AGNR, while its highest occupied molecular orbital (HOMO) energy level remained constant within the given AGNR length. Furthermore, we prepared, for the very first time, N = 5 AGNR block copolymers with widely used donor or acceptor-conjugated polymers by taking advantage of the living SCTP. Finally, we achieved the lateral extension of AGNRs from N = 5 to 11 by oxidative cyclodehydrogenation in solution and confirmed their chemical structure and low band gap by various spectroscopic analyses.

Syntheses of Diarylmethanes via Silver or Synergic Silver/Scandium-Catalyzed Benzannulation Reactions

Syntheses of Diarylmethanes via Silver or Synergic Silver/Scandium-Catalyzed Benzannulation Reactions

N-Heterocyclic carbene catalyzed synthesis of benzotrifluorides from enals and β-trifluoromethylenones

An NHC-catalyzed benzannulation reaction of enals and β-trifluoromethylenones is developed for the synthesis of benzotrifluorides.

Catalytic Benzannulation Reactions of Enynones for Accessing Heterocycle-Incorporating Diarylmethanes

AbstractTwo catalytic benzannulation/1,4-addition cascades of available enynones with indoles or tetronic acid-derived enamino lactones as C-nucleophiles are reported, producing 53 examples of heterocycle-incorporating diarylmethanes with moderate to excellent yields. The combination of AgOTf and Sc(OTf)3 permits bimetallic synergistic catalysis of the reaction of enynones with indoles to access 35 triarylmethanes in generally good yields with ortho-naphthoquinone methides, generated in situ, as the key intermediates. Exchanging indoles for tetronic acid-derived enamino lactones resulted in 18 diarylmethanes by the Ag-catalyzed benzannulation/1,4-addition cascade. Both reactions are advantageous for their high atom utilization and mild reaction conditions, providing intriguing complementary approaches for the direct syntheses of new heterocycle-containing diarylmethanes.

“Back‐to‐Front” Indole and Carbazole Synthesis from N,N‐Bis‐(2‐bromoallyl)amines by Combining Carbolithiation Reactions with Gold‐Catalysis

AbstractThe combination of organolithium chemistry with gold catalysis has enabled the development of a synthetic strategy for accessing polysubstituted indoles and carbazoles from readily available starting materials. This method is based on a “back‐to‐front” approach from ketopyrroles, generated by intramolecular carbolithiation of N,N‐bis‐(2‐lithioallyl)amines that evolve into 3,4‐bis(lithiomethyl)dihydropyrrole intermediates capable of reacting with carboxylic esters and Weinreb amides. These ketopyrroles have demonstrated to be excellent precursors of mono or bis(alkynols)pyrroles that, under gold‐catalysis, experience a benzannulation reaction providing access to regioselectively substituted indoles or carbazoles.magnified image

Dimethyl Sulfoxide-Assisted, Iodine- and Ascorbic Acid-Catalyzed One-Pot Synthetic Approach for Constructing Highly Substituted Pyrazolo[1,5-a]quinoline Thioether Derivatives.

A dimethyl sulfoxide-assisted and iodine/ascorbic acid-catalyzed simple approach to pyrazolo[1,5-a]quinoline thioether derivatives 22 is described. The compounds were identified using 1H NMR, 13C NMR, high-resolution mass spectrometry, and single-crystal X-ray diffractometry. The pyrazolo[1,5-a]quinoline thioether was synthesized in a stepwise fashion through aryl sulfenylation and benzannulation strategies. The generated heteroaryl thioether compounds 23 were exposed to the benzannulation path to produce pyrazolo[1,5-a]quinoline thioether 22. The benzannulation reaction proceeds by way of diazotization of the pyrazole amine derivative 23, radical generation by the removal of nitrogen, and eventually trapping of the aryl radical with the support of phenylacetylene 19. A catalytic amount of ascorbic acid aided the benzannulation reaction. There were several other control studies conducted, including trapping reactions with isopropenyl acetate, tetramethylpiperidine N-oxyl reactions, and reactions without phenylacetylene. Since a change in the substitution has previously demonstrated substantial bioactivity, the core structure of pyrazole was evaluated for functional group tolerance. A reasonable mechanism is then proposed, accompanied by the support of control experiments and scope. A Suzuki reaction was used to create an aryl/heteroaryl compound 35 from one of the synthesized compounds 22b. In the controlled oxidation reaction paths, molecule 22a was selectively transformed into the corresponding sulfoxide 32 and sulfone 33.

Domino Reactions through Recursive Anionic Cascades: The Advantageous Use of Nitronates

AbstractRecursive Anionic Cyclization (RAC) continues to proliferate as a mechanistically distinct domino strategy. Deployment of nitroalkanes as a source of recursive carbanions has created a niche operating space for generating molecular complexity and diversity. This new corollary i. e. recursive nitronate cyclization is the basis of a domino [5 C+1 C] cyclization strategy wherein nitroalkanes act as one‐carbon lynchpin, providing rapid access to topologically intriguing, densely functionalized carbo‐ and heterocycles embodying multiple chiral centers with regio‐, stereo‐ and enantioselectivity. Extension to aromatic domains, particularly via benzannulation reactions, has further consolidated the operating space. While leveraging the functional versatility of nitro group for post‐domino modifications, such endeavors have culminated in total synthesis of diverse natural products. An incisive analysis of recursive nitronate cyclizations and their emergent potentials is delineated in this review. It is hoped that this focused narrative will enthuse and draw new practitioners to the arena to advance the field.

π‐Extended Helical Nanographenes: Synthesis and Photophysical Properties of Naphtho[1,2‐a]pyrenes**

AbstractA mild and efficient synthesis of a broad scope of substituted naphtho[1,2‐a]pyrene derivatives was accomplished in good yields using an InCl3/AgNTf2‐mediated two‐fold alkyne benzannulation reaction. HPLC enantiomeric separation was achieved and the interconversion barriers have been determined. The ECD spectra of two derivatives were recorded and interpreted through TD‐DFT calculations. Raman spectra were also recorded and predicted through DFT calculations.

Cover Picture: Benzannulation Reactions: A Case for Perspective Change From Arene Decoration to Arene Construction (Chem. Rec. 1/2022)

The cover picture shows recreations of the ancient symbol ‘ouroboros'. The most common depiction of the latter, a snake swallowing its own tail, is perhaps the oldest allegorical symbol in renaissance alchemy. August Kekulé's subconscious deciphered the structure of benzene by invoking this very symbol in his famous daydream. Chemists who endeavour to synthesize arenes can also draw inspiration from ouroboros, as depicted here. At their disposal are numerous acyclic building blocks (snakes) that may be combined to form substituted arenes by benzannulation reactions, a versatile alternative to aromatic substitutions. See the review by R. Menon and co-workers (DOI: 10.1002/tcr.202100249).

Bringing out the potential of organoboron compounds by designing the chemical bonds and spaces around boron.

Since the structures, reactivity and properties of organoboron compounds stem from the electron deficiency and low electronegativity of boron, the design of the chemical bonds attached to boron as well as the space provided by substituents around boron leads to particular reactivity and functions of organoboron compounds. Based on the concept of vacant boron p-orbital engineering in combination with peripheral space design for boron, we have developed new organoboron compounds, which exhibit exotic reactivity and properties and boron-mediated organic transformations capable of constructing large π-conjugated systems. Here we describe our recent study by focusing on three topics: (i) the synthesis and its derivatization, small-molecule activation and application to materials science of a two-coordinate boron cation (borinium ion), (ii) a 9-borafluorene-mediated benzannulation reaction of alkyne derivatives and (iii) BN-substituted molecules featuring a 4nπ heterocycle exhibiting unique electronic and emission properties. The molecules and reactions appearing in this article are unprecedented, yet feature very simple systems, and therefore clearly demonstrate intrinsic and new potential of organoboron compounds.

Hetero-Type Benzannulation Leading to Substituted Benzothio-Phenes.

TiCl4 (or SnCl4)-promoted hetero-type benzannulation reactions using various (2,2-dichlorocyclopropyl)(thiophen-2-yl)methanols proceeded smoothly to produce uniquely substituted 4-chlorobenzothiophenes (five examples). The present approach involves the first distinctive thiophene formation from thiophene cores, in contrast to traditional methods of thiophene formation from benzene cores. The stereocongested (less reactive) Cl position in the obtained 4-chlorobenzothiophenes functioned successfully as the partners of three cross-coupling reactions: (i) a Suzuki–Miyaura cross-couplings using Pd(OAc)2/SPhos/K3PO4 catalysis (seven examples; 63–91%), (ii) a hydroxylation using KOH/Pd(dba)2/tBu-XPhos catalysis (85%), and (iii) a borylation using a B2(pin)2/Pd(dba)2/XPhos/NaOAc catalysis-provided 4-(pin)B-benzothiophene (58%).

Benzannulation Reactions: A Case for Perspective Change From Arene Decoration to Arene Construction.

Benzannulation reactions involve construction of a benzene ring from acyclic precursors. This class of reactions offer a versatile and often superior alternative to aromatic substitution for construction of substituted arenes. Selected pioneering and recent reports of various benzannulation reactions are categorised and discussed in this review.

Base‐mediated Benzannulation Reactions for the Synthesis of Densely Functionalized Aryl α‐Keto Esters

AbstractA novel and straightforward strategy for the construction of versatile densely functionalized aryl α‐keto esters is disclosed through a one‐pot and efficient [4+2] benzannulation reaction of α‐cyano‐β‐methylenones and ynediones, which could be synthesized easily from the corresponding starting materials. This protocol features high yield, mild metal‐free reaction condition, high atom economy, high functional‐group tolerance, easy handing and gram‐scale synthesis.