Friedel Crafts-type Cyclization Research Articles

Heptagon/Octagon-Fused Diporphyrins or Spiro-Pentagon-Bridged Dichlorin from p-Terphenylene-Bridged Diporphyrin.

Intramolecular fusion reactions of a p-terphenylene-bridged NiII porphyrin dimer gave different products, depending upon reaction conditions. Oxidation with Fe(OTf)3 provided syn- and anti-doubly heptagon-fused NiII porphyrin dimers showing enlarged π-electronic networks, probably via a radical mechanism, while treatment with methanesulfonic acid provided a spiro-pentagon-bridged NiII chlorin dimer via acid-catalyzed Friedel-Crafts type cyclization. Further, a doubly octagon-fused NiII porphyrin dimer was synthesized via a sequence of double meso-formylation, reduction to corresponding diol, and BF3 -catalyzed cyclization.

Silylium Ion Initiated Intramolecular Friedel–Crafts-Type Cyclization of 1,1-Difluoroalkenes with Subsequent Hydrodefluorination of C(sp3)–F Bonds

AbstractThe strong electrophilicity of silylium ions has been leveraged to probe an intramolecular Friedel–Crafts-type cyclization of aryl-tethered 1,1-difluoroalkenes. The reaction is presumed to be initiated by a preferential electrophilic silylation of the carbon–carbon double bond over the activation of one of the vinylic C(sp2)–F bonds. Subsequent cyclization followed by hydrodefluorination of the resulting C(sp3)–F bonds leads to the final product. The resulting tetraline derivatives were obtained in moderate to good yields. Distinct from earlier reports, the reaction proceeds with the perfluorinated tetraphenylborate counteranion under ambient conditions without the prerequisite of a carborate counteranion associated with the silylium ion intermediates.

Construction of Substituted [4]Acene Frameworks Based on Double Cationic Cyclizations of Fluoroalkenes

AbstractIn this study, 5-substituted and 5,6-disubstituted [4]acenes were synthesized by the double cationic cyclization of fluoroalkenes. (a) After being treated with Me2AlCl (1.2 equiv), 2-trifluoromethyl-1-alkenes bearing two aryl groups underwent domino Friedel–Crafts-type cyclization (two-ring construction) followed by dehydrogenation to generate 5-fluorinated [4]acenes. The same (trifluoromethyl)alkenes were treated with both Me2AlCl (1.2 equiv) and Me3Al (1.0 equiv), resulting in selective one-ring construction and the creation of bicyclic 1,1-difluoro-1-alkenes. (b) When treated with triflic acid, the bicyclic difluoroalkenes underwent regioselective protonation to generate CF2 cations; Friedel–Crafts-type cyclization of these cations provided tetracyclic ketones. The obtained ketones act as an appropriate platform for the introduction of substituents at the 5-position of [4]acenes. (c) When treated with DDQ/H+, the bicyclic difluoroalkenes underwent oxidative generation of allylic CF2 cations; Friedel–Crafts-type cyclization of these cations produced tetracyclic enones. The enones were subjected to double addition of carbanions to facilitate the introduction of two substituents at the 5- and 6-positions of dihydro[4]acenes.

Silyl Cyanopalladate-Catalyzed Friedel–Crafts-Type Cyclization Affording 3-Aryloxindole Derivatives

Abstract3-Aryloxindole derivatives were synthesized through a Friedel–Crafts-type cyclization. The reaction was catalyzed by a trimethylsilyl tricyanopalladate complex generated in situ from trimethylsilyl cyanide and Pd(OAc)2. Wide varieties of diethyl phosphates derived from N-arylmandelamides were converted almost quantitatively into oxindoles. When N,N-dibenzylamide was used instead of an anilide substrate, a benzo-fused δ-lactam was obtained. An oxindole product was subjected to substitution reactions to afford 3,3-diaryloxindoles with two different aryl groups.

Practical Synthesis of 1-Substituted 5-Aminopyrazolo[4,3-d]pyrimidin-7-ones Using Intramolecular Friedel–Crafts Type Cyclization and Its Application to the Synthesis of Pharmaceutically Active Compounds

Practical Synthesis of 1-Substituted 5-Aminopyrazolo[4,3-d]pyrimidin-7-ones Using Intramolecular Friedel–Crafts Type Cyclization and Its Application to the Synthesis of Pharmaceutically Active Compounds

Integrated Synthesis of Thienyl Thioethers and Thieno[3,2-b]thiophenes via 1-Benzothiophen-3(2H)-ones

AbstractA one-pot procedure for the synthesis of thienyl thioethers is described. Several thienyl thioethers were synthesized by a TfOH-promoted Friedel–Crafts-type cyclization, a subsequent nucleophilic attack by an arenethiol, and dehydration. This protocol was successfully applied to the synthesis of thienoacene derivatives by using a Pd-catalyzed dehydrogenative cyclization.

Boron-Nitrogen-Doped Nanographenes: A Synthetic Tale from Borazine Precursors.

In this work, a comprehensive account of the authors' synthetic efforts to prepare borazino-doped hexabenzocoronenes by using the Friedel-Crafts-type electrophilic aromatic substitution is reported. Hexafluoro-functionalized aryl borazines, bearing an ortho fluoride leaving group on each of the N- and B-aryl rings, was shown to lead to cascade-type electrophilic aromatic substitution events in the stepwise C-C bond formation, giving higher yields of borazinocoronenes than those obtained with borazine precursors bearing fluoride leaving groups at the ortho positions of the B-aryl substituents. By using this pathway, an unprecedented boroxadizine-doped PAH featuring a gulf-type periphery could be isolated, and its structure proven by single-crystal X-ray diffraction analysis. Mechanistic studies on the stepwise Friedel-Crafts-type cyclization suggest that the mechanism of the planarization reaction proceeds through extension of the π system. To appraise the doping effect of the boroxadizine unit on the optoelectronic properties of topology-equivalent molecular graphenes, the all-carbon and pyrylium PAH analogues, all featuring a gulf-type periphery, were also prepared. As already shown for the borazino-doped hexabenzocoronene, the replacement of the central benzene ring by its B3 N2 O congener widens the HOMO-LUMO gap and dramatically enhances the fluorescence quantum yield.

One-Pot Synthesis of Spirocyclopenta[a]indene Derivatives via a Cascade Ring Expansion and Intramolecular Friedel-Crafts-Type Cyclization.

A one-pot efficient synthetic approach for the rapid construction of spirocyclopenta[a]indene derivatives has been developed via an iodine-initiated cascade ring expansion and intramolecular Friedel-Crafts-type cyclization from propargyl alcohol-tethered alkylidenecyclobutanes under mild conditions with broad substrate scope. This cascade process can be elegantly conducted on a gram scale. A plausible reaction mechanism has been proposed on the basis of a series of deuterium labeling and control experiments.

Silver-Mediated Intramolecular Friedel–Crafts-Type Cyclizations of 2-Benzyloxy-3-bromoindolines: Synthesis of Isochromeno[3,4-b] indolines and 3-Arylindoles

We disclose a silver-mediated intramolecular Friedel–Crafts-type cyclization of 2-benzyloxy-3-bromoindolines to afford an untapped family of isochromeno[3,4-b]indolines and 3-arylindoles, in which deformylative arylation of 2-(4-methoxybenzyloxy)-3-bromoindolines is reported for the first time. The isochromeno[3,4-b]indolines can be readily transformed into other heterocyclic moieties.

Methylarene-Based PAH Synthesis via Domino Cyclization of 1,1-Difluoro-1-alkenes

Abstract Polycyclic aromatic hydrocarbons (PAHs) containing 4–7 benzene rings were synthesized via a methylarene-based protocol. Trimethyl[2-(trifluoromethyl)allyl]silane was electrophilically benzylated with Ar1CH2Br (prepared from Ar1CH3) to afford 2-trifluoromethyl-1-alkenes that were in turn nucleophilically benzylated with Ar2CH2Li (prepared from Ar2CH3) through an SN2′-type reaction to produce 1,1-difluoroethylenes, which are cyclization precursors bearing two 2-arylethyl groups. Magic acid efficiently promoted the domino Friedel–Crafts-type cyclization of these precursors, followed by dehydrogenation that enabled the connection among two aryl groups (Ar1 and Ar2) by forming two benzene rings between them, facilitating the synthesis of the desired higher-order PAHs. With the proposed protocol, the combination of even a limited number of methylarenes can yield a variety of PAHs in diverse configurations.

Synthesis of the ABCDG ring skeleton of communesin F based on carboborylation of 1,3-diene and Bi(OTf)3-catalyzed cyclizations.

Communesins, isolated from the mycelium of a strain of Penicillium sp., are cytotoxic heptacyclic indole alkaloids bearing a bis-aminal structure and two contiguous quaternary carbon centers. Toward a total synthesis of communesin F, we synthesized a pentacyclic ABCDG ring skeleton via carboborylation of 1,3-diene and a Friedel-Crafts-type cyclization, resulting in the formation of an azepine ring through a Bi(OTf)3-catalyzed SN2' reaction.

Microwave Irradiation Effect on Friedel-Crafts Type Cyclization Reaction

Background: Isoquinolones are widely used compounds as bioactive substances and antibiotics. Therefore, it is important to establish their synthetic process. One possibility for this purpose is the use of Curtius rearrangement. Such reactions are applied to produce heterocycles containing nitrogen atom. In this study, shortening of the synthetic process is discussed using the Friedel-Crafts type cyclization reaction. Furthermore, high yields and highly selective reactions are required during the microwave irradiation. Methods: The reactions were carried out under microwave irradiation conditions as well as conventional heating conditions. The microwave irradiation effect was investigated by comparing their yields. Results: The reactions occurred in several nonpolar solvents. Especially, in decalin, the yields under the microwave irradiation conditions were higher than under the conventional heating conditions. This would be due to selective absorption of microwaves by the substrates. For the improvement of the yields, the Friedel-Crafts type cyclization reactions were carried out in the presence of FeCl3. The addition of FeCl3 at a higher temperature would not be effective for this Friedel-Crafts type cyclization reaction. The use of FeCl3 enable to proceed the reaction at lower temperature. Conclusion: The microwave accelerating effect was observed in a nonpolar solvent. In this solvent, microwaves would be selectively absorbed not by the solvent, but by the substrate. Furthermore, by the use of FeCl3 as a catalyst, the reaction was able to proceed at a lower temperature. This would result in the adduct formation between the substrate and FeCl3. These results show that the microwave irradiation can be a potential tool to proceed the Friedel-Crafts type cyclization reaction, but further optimization of the reaction conditions would be required. Keywords: Cyclization reaction, friedel-crafts reaction, heterocycle, iron(III) chloride, isoquinolone, microwave.

Pinpoint-fluorinated polycyclic aromatic hydrocarbons (F-PAHs): Syntheses of difluorinated subfamily and their properties

Difluorinated polycyclic aromatic hydrocarbons (PAHs) containing three to five benzene rings were systematically synthesized by the Pd(II)-catalyzed Friedel–Crafts-type cyclization of 1,1,2-trifluoro- and 1,1-difluoro-1-alkenes and the In(III)-catalyzed tandem cyclization of bis(1,1-difluoroallene)s. Using an array of the difluorinated PAHs that were obtained and previously reported monofluorinated PAHs, the physical properties of the pinpoint-fluorinated PAHs were investigated. (i) The 19F NMR signals of the bay-region fluorine atoms were shifted downfield by ca. 8–14ppm for vic-difluorinated PAHs and ca. 11–19ppm for non-vic-difluorinated and monofluorinated PAHs. (ii) The introduction of fluorine into PAH molecules increased their solubilities in organic solvents, which was best exemplified by the high solubilities of 6,7-difluoropicene (5.4wt%) and 6-fluoropicene (5.3wt%) in THF. (iii) The HOMO–LUMO energy gaps of the pinpoint-fluorinated PAHs were smaller than that of the corresponding fluorine-free PAH (i.e., picene) by 0.02–0.26eV, and the HOMO and LUMO energy levels were lowered by 0.10–0.22eV and 0.12–0.41eV, respectively.

ChemInform Abstract: Copper‐Catalyzed Tandem Arylation—Cyclization of 2‐Alkynylaryl Isothiocyanates with Diaryliodonium Salts: An Efficient Synthesis of Thiochromeno[2,3‐b]indoles.

A catalytic tandem arylation–cyclization approach using 2-alkynylphenyl isothiocyanates with diaryliodonium salts is described. The reaction is performed under mild conditions and thiochromeno[2,3-b]indoles are obtained in moderate to good yields. This tandem protocol involves chemoselective S-arylation, regioselective 5-endo-trig cyclization and Friedel–Crafts-type cyclization processes. Two C–C bonds, one C–S bond, and two heterocyclic rings are formed in a single step. Preliminary mechanistic studies indicate that a carbocation mechanism is involved.

ChemInform Abstract: Enantioselective Organocatalytic Construction of Spiroindane Derivatives by Intramolecular Friedel—Crafts‐Type 1,4‐Addition.

AbstractA highly selective organocatalytic enantioselective intramolecular Friedel—Crafts type cyclization of cycloalkenone onto a resorcin‐type substituent is developed to give a range of spirocyclic indanes.

ChemInform Abstract: Hendrickson‐Reagent‐Mediated Conversion of N‐Boc Carbamates to Isocyanates: Applications for the Synthesis of 3,4‐Dihydroisoquinolin‐1‐ones and Ureas.

An efficient method for isocyanate formation from N-Boc carbamates was developed utilizing a Hendrickson “POP” reagent as a dehydrating agent. By using this reagent, isocyanates were formed preferentially from N-Boc carbamates over other carbamates. The reaction could be paired with successive reactions such as Friedel–Crafts-type cyclization and urea formation.

Copper-catalyzed tandem arylation–cyclization of 2-alkynylaryl isothiocyanates with diaryliodonium salts: an efficient synthesis of thiochromeno[2,3-b]indoles

A Cu-catalyzed arylation–cyclization approach is developed for the synthesis of thiochromeno[2,3-b]indoles through the S-arylation, 5-endo-trig cyclization, and Friedel–Crafts-type cyclization sequence.

Pinpoint-fluorinated phenanthrene synthesis based on CF bond activation of difluoroalkenes

Abstract Treatment with a cationic palladium(II) catalyst promoted the Friedel–Crafts-type cyclization of 1,1-difluoro-1-alkenes bearing a biphenyl skeleton to afford regioselectively fluorinated (pinpoint-fluorinated) phenanthrenes via C F bond activation. The obtained pinpoint-fluorinated phenanthrenes were observed to be organized by π–π and C H⋯F interactions to exhibit columnar and layer structures in the solid state.

Facile synthetic protocols for perfluoroalkyl-substituted diazapentaphenes

Novel syntheses of 13,14-bis(perfluoroalkyl)-substituted 5,8-diazapentaphene derivatives were realized by such a facile two-step protocol as consecutive benzyne insertion into C(O)–NH bonds of p-phenylene-bis(perfluoroalkanamides), followed by Friedel–Crafts type cyclization reaction, yielding the corresponding title compounds especially for the case of Rf=CF3 or C2F5. Additionally, an alternative approach based on condensation of cyclohexane-1,4-dione with (o-aminophenyl) perfluoroalkyl ketones, followed by dehydrogenation enabled us to effectively access to the same final products in better yields.

Synthesis and Optoelectronic Properties of Hexahydroxylated 10‐O‐R‐Substituted Anthracenes via a New Modification of the Friedel–Crafts Reaction Using O‐Protected ortho‐Acetal Diarylmethanols

A new modification of the Friedel-Crafts type intramolecular cyclization involving O-protected ortho-acetal diarylmethanols as a new type of reactant, was carried out for the first time in a medium containing a large amount of water at room temperature and enabled synthesis of a series of electron-rich, hexahydroxylated 10-O-R-substituted anthracenes, where R is an alkyl (Me, nBu, n-C(16)H(33)) or arylalkyl group (CH(2)Ph, CH(2)-2-Napht, CH(2)C(6)H(4)CH(2)OAr) and also evaluation of their electronic and optoelectronic properties in solution, crystal, and solid thin film. In this transformation, a central 10-O-R-substituted benzene ring was formed, fused to rings originating from two independent aromatic aldehydes. The reaction proceeded via two identified mechanisms involving acetal and/or free aldehyde groups. The acid sensitive acetal and dibenzyl alkoxy functions have never been used together in the intramolecular Friedel-Crafts type cyclization. The new compounds revealed deep blue fluorescence and quantum yields in solution around 0.3. The electrical properties investigated for thin films obtained by vacuum deposition on glass were 10-O-R-substituent dependent and showed much faster transient current decay in the case of the 10-O-CH(2)Ph derivative than for the material with a 10-O-Me substituent (the lifetime of charge carriers was 25 times shorter in this case). The AFM images of thin films, Stokes shifts, and X-ray analysis of π-stacking interactions in crystals of the new materials have been also obtained.