Functionalized Benzo Research Articles

Visible-Light-Promoted Radical Cascade Cyclization of 2-Vinyl Benzimidazoles: Access to Benzo[4,5]imidazo[1,2-b]isoquinolin- 11(6H)-ones.

A visible-light-enabled photoredox radical cascade cyclization of 2-vinyl benzimidazole derivatives is developed. This chemistry is applicable to a wide range of N-aroyl 2-vinyl benzimidazoles as acceptors, and halo compounds, including alkyl halides, acyl chlorides and sulfonyl chlorides, as radical precursors. The Langlois reagent also serves as an effective partner in this photocatalytic oxidative cascade process. This protocol provides a robust alternative for rendering highly functionalized benzo[4,5]imidazo[1,2-b]isoquinolin-11(6H)-ones.

Ag-Catalyzed Synthesis of Functionalized Benzo[d]azepines

Ag-Catalyzed Synthesis of Functionalized Benzo[d]azepines

Hydroxyl-Directed Rh(III)-Catalyzed C-H Functionalization: Access to Benzo[de]chromenes.

A cascade oxidative annulation reaction of heterocyclic ketene aminals (HKAs) with internal alkynes catalyzed by [Cp*RhCl2]2 and oxidized by Cu(OAc)2·H2O was developed to efficiently synthesize highly functionalized benzo[de]chromene derivatives in good to excellent yields. The reaction proceeded by the sequential cleavage of C(sp2)-H/O-H and C(sp2)-H/C(sp2)-H bonds. These multicomponent cascade reactions were highly regioselective. In addition, all of the benzo[de]chromene products exhibited intense fluorescence emission in the solid state, and they demonstrated concentration-dependent quenching in the presence of Fe3+, indicating that these compounds could be used in the recognition of Fe3+.

Synthesis of benzo[b][1,5]diazocin-6(5H)-one derivatives via the Cu-catalysed oxidative cyclization of 2-aryl-1H-indoles with 1,1-enediamines.

A novel protocol for the synthesis of highly functionalized benzo[b][1,5]diazocin-6(5H)-one derivatives (BDCOs, 4 and 5) from 2-aryl-1H-indoles and 1,1-enediamines was developed via a complex cascade of reactions including regioselective free radical oxidation, the 1,2-addition of imine, imine-enamine tautomerization, intramolecular cyclization, and ring expansion. The cascade reaction was enabled by refluxing a mixture of two substrates in the presence of di-tert-butyl peroxide (DTBP) as an oxidant and anhydrous CuI as a catalyst in toluene under argon protection. Consequently, a series of BDCOs (4 and 5) were synthesized with high regioselectivity in good yield. This protocol can be used for the synthesis of functionalized BDCOs via a one-pot oxidative annulation reaction rather than a multi-step reaction, which is suitable for both combinatorial and parallel syntheses of BDCOs.

Rhodium(III)-Catalyzed Dehydrogenative Annulation and Spirocyclization of 2-Arylindoles and 2-(1H-Pyrazol-1-yl)-1H-indoles with Maleimides: A Facile Access to Isogranulatimide Alkaloid Analogues.

A Rh(III)-catalyzed dehydrogenative annulation and spirocyclization of 2-arylindoles and 2-(1H-pyrazol-1-yl)-1H-indole with maleimides is described. The cascade protocol provided highly functionalized benzo[a]pyrrolo[3,4-c]carbazole-1,3(2H,8H)-diones and spiro[isoindolo[2,1-a]indole-6,3'-pyrrolidine]-2',5'-diones in good to excellent. The developed reaction methodology exhibited broad substrate scope with good functional group tolerance and is operationally simple and scalable. Photophysical properties of the annulated products were investigated. The annulated product of 2-(1H-pyrazol-1-yl)-1H-indole showed high absorption and emission values with a large red-shift as compared to that of 2-phenylindole.

A Facile Regioselectively Synthesis of 2‐Alkenylbenzo[1,2‐b:4,5‐b’]dithiophene by Pd/Cu/Ag‐Catalyzed C‐H Functionalization

AbstractIn this work, several alkenylated benzo[1,2‐b:4,5‐b′]dithiophene were synthesized by Pd‐catalyzed C−H functionalization of benzo[1,2‐b:4,5‐b′]dithiophene with various alkenes. This direct alkenylation took place regioselectively at the C‐2 position of the fused heterocycle. The obtained compounds were structurally characterized by NMR and MS spectroscopic methods. Moreover, DFT calculations have been employed to shed light on the regioselectivity of the reaction as well as on the geometry and electronic properties of the newly formed C=C double bonds.

One‐pot synthesis of highly functionalized benzo [1,3] thiazine from isocyanides, aniline, and heterocumulene via Cu‐catalyzed intramolecular C‐H activation reactions

AbstractA one‐pot synthesis of functionalized benzo thiazine derivatives via a Cu‐catalyzed, multicomponent reaction of isocyanides, aniline, and heterocumulenes in acetonitrile at room temperature was developed. Transition metal‐catalyzed activation of C‐H bonds under mild copper‐catalytic reaction conditions, using simple and available starting materials, also obtaining a pure product with high yield without applying column chromatography are the major advantages of the applied method among the other ones used for this purpose. The structures are confirmed spectroscopically (1H‐ and 13C‐NMR, IR, and EI‐MS) and through elemental analyses.

On Water: Metal-Free Synthesis of Highly Functionalized Benzothiazolylidene from ortho-Haloanilines.

An environmentally benign, transition-metal-free organic base promoted one-pot cascade synthesis of highly functionalized benzo[ d]thiazol-2(3 H)-ylidene benzamide in the presence of water was accomplished by three-component reaction of ortho-iodoanilines, acrylates, and aroyl isothiocyanates. The protocol involves the in situ generation of thiourea intermediate followed by triethylamine induced intramolecular SNAr displacement reaction and subsequent Michael addition onto acrylate leads to the formation of benzo[ d]thiazol-2(3 H)-ylidene benzamide. Benzo[ b]thiazole is also generated in good yields using amidation and intramolecular aromatic nucleophilic substitution chemistry. The control experiments support the proposed mechanistic pathway. Further X-ray crystallographic studies confirmed the assigned structures of the fused benzamide.

Two step, one-pot sequential synthesis of functionalized hybrid polyheterocyclic scaffolds via a solid state melt reaction (SSMR).

A new one pot assembly of highly functionalized benzo[a]phenazinone fused chromene/bicyclic scaffolds via a domino Knoevenagel intramolecular hetero-Diels–Alder (IMHDA) strategy using a solid state melt reaction (SSMR) of 2-hydroxynaphthalene 1,4-dione, o-phenylenediamine, O-allyl salicylaldehyde/O-vinyl salicylaldehyde derivatives is reported. The formation of five new bonds (two C–C bonds and three C–O bonds), three six-membered rings, and three stereogenic centers in a one-pot manner is very attractive. Ease of reaction with short time, good yields with water as the only byproduct and work up free procedure are some of the excellent features of the present protocol.

Ultrasound-assisted synthesis of highly functionalized benzo[1,3]thiazine via Cu-catalyzed intramolecular C[sbnd]H activation reaction from isocyanides, aniline-benzoyl(acetyl) isothiocyanate adduct

A facile sonochemical route for the synthesis of benzo[1,3]thiazine derivatives via a one pot, multicomponent, intramolecular CH activation reaction from isocyanides, aniline and benzoyl (acetyl) isothiocyanate adduct catalyzed by copper (I) iodide in acetone at 30 °C have been reported. The advantages of the described method include using simple and readily available starting materials and performing under mild copper-catalytic reaction conditions and also obtaining pure product with high yield without applying column chromatography. Furthermore, using the sonochemical methodology as an efficient method led to reduce the reaction times.

Thiacycle-fused benzo[1,2-b:4,5-b′]dithiophenes (BDTs): synthesis, packing, molecular orientation and semiconducting properties

Functionalization of benzo[1,2-b:4,5-b′]dithiophenes (BDTs) with thiacycles to selectively tune the packing, molecular orientation and semiconducting properties is systematically studied.

Palladium-Catalyzed Intramolecular Fujiwara-Hydroarylation: Synthesis of Benzo[a]phenazines Derivatives.

An atom-economical Pd-catalyzed approach for the synthesis of benzophenazine derivatives using substituted 2-aryl-3-(aryl/alkylethynyl) quinoxaline in the presence of trifluoroacetic acid at 65 °C has been described. The chemistry involves in situ generation of cationic Pd(II) species, which functionalized the aromatic C-H bonds via electrophilic metalation followed by concomitant intramolecular trans-insertion of C-C triple bond to aryl-Pd complex. The results were supported by various control experiments including with electron-deficient arenes and deuterium labeling studies. The deuterium labeling studies supports electrophilic palladation of aromatic C-H over activation of C-C triple bond of alkyne. The structure of synthesized compounds was further confirmed by X-ray crystallography studies. This catalytic protocol has been efficiently applied for novel synthesis of highly functionalized benzo fused phenazines.

Transition‐Metal‐Free Thiolation Annulation of 2‐Fluorophenylacetylene Derivatives: Expedient Synthesis of Benzo[b]thiophenes Using Na2S•9H2O

AbstractWe present here valuable extensions to our previous work in preparing highly functionalized benzo[b]thiophene via thiolation annulation of 2‐fluorophenylacetylene derivatives using Na2S•9H2O under transition‐metal‐free conditions. This practical process was initiated by a Na2S•9H2O induced providing 2‐alkynyl benzenethiol, followed by annulation process affording the corresponding benzo[b]thiophene in moderate to good yields from simple and readily available starting materials.

ChemInform Abstract: Precursor Directed Regioselective Synthesis of Partially Reduced Benzo[e]indene Through Oxidative Cyclization and Benzo[h]quinolines.

We have reported a simple, unprecedented base promoted synthesis of 7-substituted-1-(2-cyano-phenyl/phenyl)-3-sec amino-4,5-dihydro-1H-benz[e]indene-1,2-dicarbonitriles by reaction of 2-oxo-4-sec amino-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles and 2-cyanomethyl-benzonitrile/phenyl-acetonitrile under basic conditions at 100 °C. This reaction involves ring opening of 2-oxo-4-sec amino-5,6-dihydro-2H-benzo[h]chromene-3-carbonitrile by a carbanion generated in situ from 2-cyanomethylbenzonitrile/phenyl-acetonitrile followed by oxidative cyclization to afford the desired product. Alternatively, reaction of 6-aryl-4-sec amino-2H-pyran-2-one-3-carbonitriles and 2-cyanomethyl-benzonitrile under basic conditions provides functionalized benzo[h]quinolines. The structure of the synthesized compound was confirmed by single crystal X-ray.

ChemInform Abstract: Synthesis and Diels—Alder Reactions of a Benzo[5]radialene Derivative.

Apart from their exotic structure, radialenes have been employed as precursors of more complex polycyclic molecules. In this work we report the synthesis of the first compound having the benzo[5]radialene substructure, starting from simple materials. Such a compound proved to be a convenient diene in Diels–Alder reactions, for the preparation of highly functionalized fluorenes and benzo[b]fluorenes in a quimio- and stereocontrolled fashion.

Stereospecific synthesis of highly functionalized benzo[3.1.0]bicycloalkanes via multistep cascade reactions

A facile approach for the synthesis of benzo[3.1.0]bicycloalkanesviaalkylation/cyclopropanation cascade reactions of benzyl bromide with triphenylphosphonium bromide.

ChemInform Abstract: Completely Regioselective Direct C—H Functionalization of Benzo[b]thiophenes Using a Simple Heterogeneous Catalyst.

The first completely selective C3 C–H arylation of benzo[b]thiophenes is reported, demonstrating previously unexploited reactivity of palladium. Benzo[b]thiophenes are coupled with readily available aryl chlorides using a ligand-free, dual catalytic system of heterogeneous Pd/C and CuCl. The reaction is operationally simple and insensitive to air and moisture, and it provides valuable products with complete selectivity. Significant investigations into the nature of the active catalytic species and mechanistic considerations are discussed.

Completely Regioselective Direct C–H Functionalization of Benzo[b]thiophenes Using a Simple Heterogeneous Catalyst

The first completely selective C3 C-H arylation of benzo[b]thiophenes is reported, demonstrating previously unexploited reactivity of palladium. Benzo[b]thiophenes are coupled with readily available aryl chlorides using a ligand-free, dual catalytic system of heterogeneous Pd/C and CuCl. The reaction is operationally simple and insensitive to air and moisture, and it provides valuable products with complete selectivity. Significant investigations into the nature of the active catalytic species and mechanistic considerations are discussed.

Microwave-Assisted Multicomponent Reactions: Rapid and Regioselective Formation of New Extended Angular Fused Aza-Heterocycles

A new multicomponent domino reaction for rapid and regioselective synthesis of highly functionalized benzo[h]naphtho[2,3-a]acridine-15,16(5H,14H)-diones has been established. The reaction can be conducted by using readily available and inexpensive substrates under microwave irradiation. The procedures are facile, avoiding timeconsuming and costly syntheses, tedious work-up and purifications of precursors as well as protection/deprotection of functional groups. This method is much more efficient due to short reaction times and easy work up. The resulting naphthoacridines have been readily converted into benzoquinoxaline-fused benzoquinoline analogues by treating with benzene-1,2-diamine under microwave irradiation. The structural assignment has been ambiguously confirmed by X-ray analysis. A new mechanism has been proposed for this new multicomponent domino process.

ChemInform Abstract: A New Rapid Multicomponent Domino Reaction for the Formation of Functionalized Benzo[h]pyrazolo[3,4‐b]quinolines.

AbstractBenzo[h]isoxazolo[5,4‐b]quinolines are also available.