Z‐Shaped Pyrrolo[3,2‐b]pyrroles and Their Transformation into π‐Expanded Indolo[3,2‐b]indoles

Sterically hindered 1,4‐dihydropyrrolo[3,2‐b]pyrroles possessing ortho‐(arylethynyl)phenyl substituents at positions‐2 and ‐5 were efficiently synthesized through a sila‐Sonogashira reaction. These unique Z‐shaped dyes showed relatively strong fluorescence in solution. Detailed optimization revealed that, in the presence of InCl₃, these alkynes readily undergo an intramolecular double cyclization to give hexacyclic products bearing an indolo[3,2‐b]indole skeleton in remarkable yields. Steady‐state UV–visible spectroscopy revealed that upon photoexcitation, the prepared Z‐shaped alkynes undergo mostly radiative relaxation leading to high fluorescence quantum yields. In the case of 7,14‐dihydrobenzo[g]benzo[6,7]indolo[3,2‐b]indoles, we believe that the substantial planarization of geometry in the excited state, is the underlying reason for the observed large Stokes shifts. The presence of additional electron‐withdrawing groups makes it possible to further alter the photophysical properties. The two‐photon absorption cross‐section values of both families of dyes were found to be modest and the nature of the excited state responsible for two‐photon absorption appeared to be strongly affected by the presence of peripheral groups. Serendipitous synthesis of unusual double‐Z‐shaped alkyne by Sonogashira and Glaser coupling is also reported.     

Synthesis of 4-methylfuro[3′,2′:5,6]benzofuro[3,2-c]pyridine

4-Methylfuro[3′,2′:5,6]benzofuro[3,2-c]pyridine ( 3 ) was synthetized from 2-acetylfuro[3,2-f]benzo[b]furan ( 4 ) or from 2-acetyl-5,6-dihydrofuro[3,2-f]benzo[b]furan ( 10 ). The key step involves a rearrangement-cyclization of azides 6 and 12 to form 4-methylfuro[3′,2′:5,6]benzofuro[3,2-c]pyridin-1(2H) one ( 7 ) and 8,9-dihydro-4-methylfuro[3′,2′:5,6]benzofuro[3,2c]pyridin-1(2H)-one ( 13 ). Introduction of an aminoalkyl chain on carbon 1 was effected by substitution of 1-chloro-4-methylfuro[3′,2′:5,6]benzofuro[3,2-c]pyridine ( 8 ).     

Palladium‐Catalyzed Asymmetric [4+3] Cyclization of Trimethylenemethane: Regio‐, Diastereo‐, and Enantioselective Construction of Benzofuro[3,2‐b]azepine Skeletons

The palladium‐catalyzed asymmetric [4+3] cyclization of trimethylenemethane donors with benzofuran‐derived azadienes furnishes chiral benzofuro[3,2‐b]azepine frameworks in high yields (up to 98 %) with exclusive regioselectivities and excellent stereoselectivities (up to >20:1 d.r., >99 % ee). This catalytic asymmetric [4+3] cyclization of Pd‐trimethylenemethane can enrich the arsenal of Pd‐TMM reactions in organic synthesis. In addition, this strategy provides an alternative approach to chiral azepines by a transition‐metal‐catalyzed asymmetric [4+3] cyclization.     

Polycyclic N‐Heterocyclic Compounds,Part 69: Synthesis of 5‐amino‐1,2‐dihydro[1]benzofuro[3,2‐d]furo[2,3‐b]pyridines and their transformations to related compounds

Reaction of 3‐(3‐cyanopropoxy)[1]benzofuran‐2‐carbonitriles with potassium tert‐butoxide gave 5‐amino‐1,2‐dihydro[1]benzofuro[3,2‐d]furo[2,3‐b]pyridines and 5‐amino‐2,3‐dihydro[1]benzofuro[3,2‐b]oxepin‐4‐carbonitriles as new ring systems. Reactions of the 5‐chloro derivative, obtained from 5‐amino‐1,2‐dihydro[1]benzofuro[3,2‐d]furo[2,3‐b]pyridine, produced a dihydrofuran ring‐opened compound and 5‐substituted compounds. J. Heterocyclic Chem.,(2011).     

Synthesis of some fused β‐carbolines including the first example of the pyrrolo[3,2‐c]‐β‐carboline system

Condensation of 1‐methyl‐β‐carboline‐3‐carbaldehyde with ethyl azidoacetate and subsequent thermolysis of the resulting azidopropenoate was used to [c] annulate a pyrrole ring onto the β‐carboline moiety, thus producing the first example of the pyrrolo[3,2‐c]‐β‐carboline ring system. The latter ring system results from cyclization at the C‐4 carbon, whereas cyclization at the N‐2 nitrogen atom also occurs to form a pyrazolo[3,2‐c]‐β‐carboline ring system. Condensation of β‐carboline‐1‐carbaldehyde with ethyl azidoacetate produced a non‐isolable intermediate, which immediately underwent cyclization, however in this case cyclization occurred via attack at the ester and the azide remained intact. The resulting 5‐azidocanthin‐6‐one was transformed to the first examples of 5‐aminocanthin‐6‐ones. β‐Carboline‐1,3‐dicarbaldehyde failed to give an acceptable reaction with ethyl azidoacetate, but did undergo selective condensation with dimethyl acetylene dicarboxylate at the C‐1 carbaldehyde with concomitant cyclization to form a highly functionalized 2‐formyl‐canthine derivative.     

Synthesis of indolo[2,3-c]coumarins and indolo[2,3-c]quinolinones via microwave-assisted base-free intramolecular cross dehydrogenative coupling

A microwave-assisted base-free intramolecular cross dehydrogenative coupling (CDC) of 3-aniline substituted coumarins and quinolinones have been developed. A broad range of indolo[2,3-c]coumarins and indolo[2,3-c]quinolinones can be easily afforded in good to high yields (up to 93%) under palladium catalysis. The method is among the most straightforward and convenient ways to access these fused polyheterocycles.     

Synthesis and Evaluation of Bioactivity of Thiazolo[3,2‐b]‐[1,2,4]‐triazoles and Isomeric Thiazolo[2,3‐c]‐[1,2,4]‐triazoles

Synthesis of 2‐(o‐nitrophenyl)‐6‐arylthiazolo[3,2‐b]‐[1,2,4]‐triazoles 4 and its isomer 3‐(o‐nitrophenyl)‐5‐arylthiazolo[2,3‐c]‐[1,2,4]‐triazoles 6 has been achieved starting from the appropriate 1‐(o‐nitrobenzoyl)‐3‐thiosemicarbazide 1 . Compound 1 on condensation with α‐haloketones gives 2‐(o‐nitrobenzoyl)hydrazino‐4‐arylthiazole hydrobromide 5 , which, on cyclization with POCl₃, affords thiazolo[3,2‐b]‐[1,2,4]‐triazoles 6 and not the isomeric thiazolo[3,2‐b]‐[1,2,4]‐triazoles 4 . This has been established by an unequivocal synthesis of 4 through polyphosphoric acid cyclization of 5‐aroylmethylmercapto‐3‐o‐nitrophenyl‐[1,2,4]‐triazole 3 . Compound 3 was synthesized by condensation of α‐haloketones with 5‐mercapto‐3‐(o‐nitrophenyl)‐[1,2,4]‐triazole 2 , obtained cyclization of 2‐(o‐nitrobenzoyl)hydrazinecarbothioamide 1 with NaOH. The antibacterial and antifungal activities of some of the compounds have also been evaluated.     

Preparation of a series of benzothieno[3,2‐b]pyridine‐3‐carbonitriles and benzofuro[3,2‐b]pyridine‐3‐carbonitriles

New and shorter routes to the benzothieno[3,2‐b]pyridine‐3‐carbonitrile and benzofuro[3,2‐b]pyridine‐3‐carbonitrile ring systems are reported. These heterocycles may function as new templates for kinase inhibitors.     

Construction of Hexahydropyrido[3,2‐c]carbazole and Hexahydropyrrolo[3,2‐c]carbazole Skeletons for the Synthesis of Related Indole Alkaloids

Synthesis of tetracyclic hexahydropyrido[3,2‐c]carbazoles ( 9a and 9b ) and hexahydropyrrolo[3,2‐c]carbazoles ( 13a and 13b ) structures was achieved via a new synthetic approach for the synthesis of related indole alkaloids such as deethylaspidospermidine and deethylibophyllidine. Hexahydropyrrolo[3,2‐c]carbazole structure was constructed for the first time starting from ethyl 4‐oxo‐cyclohexanecarboxylate in seven steps. Some tetrahydrocarbazole derivatives ( 4 , 5 , 6 , 7 , 11 , and 12 ) were also synthesized.     

Synthesis and Chemical Reactivity of Pyrano[3,2‐c]quinolinones

The present review covers the methods developed for the synthesis of different pyrano[3,2‐c]quinolinones as well as the chemical reactivity of these compounds towards various types of chemical reactions.     

Revisiting Indolo[3,2‐b]carbazole: Synthesis,Structures, Properties,and Applications

Indolo[3,2‐b]carbazole presents a π‐skeleton with a remarkable electronic structure and interesting potential applications. It is, however, also associated with ambiguity and controversy. Herein, new derivatives of indolo[3,2‐b]carbazole are reported and they have enabled a comprehensive study on the electronic structure of indolo[3,2‐b]carbazole and the development of a new n‐type organic semiconductor. Experimental and computational studies show that indolo[3,2‐b]carbazole has a largely localized p‐benzoquinonediimine moiety and significant antiaromaticity. When substituted with (4‐silylethynyl)phenyl groups, the indolo[3,2‐b]carbazole exhibits one‐dimensional π–π stacking and functions as an n‐type organic semiconductor in solution‐processed field effect transistors.     

Synthesis and Photooxygenation of Furo[3,2‐c]coumarin Derivatives as Antibacterial and DNA Intercalating Agent

Syntheses of 2,3‐dimethyl‐4H‐furo[3,2‐c]coumarin and 3‐phenyl‐4H‐furo[3,2‐c]coumarin as angular furocoumarins were carried out through Williamson reaction of 4‐hydroxycoumarin with α‐haloketones followed by cyclization. Photooxygenation of the synthesized furocoumarin derivatives was performed and the photoproducts were isolated and characterized. The affinity of 2,3‐dimethyl‐4H‐furo[3,2‐c]coumarin towards DNA and the antibacterial activity were evaluated and compared with 8‐methoxypsoralen (8‐MOP).     

Polycyclic N‐Heterocyclic Compounds,Part 72: Reaction of N‐([1]Benzofuro (or Benzothieno)[3,2‐d]pyrimidin‐4‐yl)formamidine and N‐(Pyrido[2,3‐d]pyrimidin‐4‐yl)formamidine Derivatives with Hydroxylamine Hydrochloride

The reactions of N‐([1]benzofuro[3,2‐d]pyrimidin‐4‐yl)formamidines with hydroxylamine hydrochloride gave rearranged cyclization products via ring cleavage of the pyrimidine component accompanied by a ring closure of the 1,2,4‐oxadiazole to give N‐[2‐([1,2,4]oxadiazol‐5‐yl)[1]benzofuran‐3‐yl)formamide oximes. N‐([1]Benzothieno[3,2‐d]pyrimidin‐4‐yl)formamidines and N‐(pyrido[2,3‐d]pyrimidin‐4‐yl)formamidines with hydroxylamine hydrochloride gave similar results.     

One‐pot Two‐step Reaction for Synthesis of Poly‐substituted Pyrano[3,2‐c]pyridones and Spiro[indoline‐3,4′‐pyrano[3,2‐c]pyridine]‐2,5′(6′H)‐diones in Water

An efficient four‐component approach for the synthesis poly‐substituted pyrano[3,2‐c]pyridones and spiro[indoline‐3,4′‐pyrano[3,2‐c]pyridine]‐2,5′(6′H)‐diones in water has been established. During the reaction, the products were readily achieved through one‐pot two‐step reaction using solid acid as catalyst. The advantages of atom and step economy, the recyclability of heterogeneous solid acid catalyst, easy workup procedure, and the wide scope of substrates make the reaction a powerful tool for assembling pyrano[3,2‐c]pyridone skeletons of chemical and medical interest.     

1,4‐Dihydropyrrolo[3,2‐b]pyrrole and Its π‐Expanded Analogues

Various approaches to the synthesis of 1,4‐dihydropyrrolo[3,2‐b]pyrroles are summarized. Many two‐ and three‐step reaction sequences have been developed, and have allowed access to a broad variety of structures, including not only the parent 1,4‐dihydropyrrolo[3,2‐b]pyrroles, but also their π‐expanded analogues. The newest approaches are critically compared with older strategies. The reactivity of these compounds is also reviewed, with special emphasis on electrophilic aromatic substitution. The synthesis of indolo[3,2‐b]indole derivatives has been the subject of intense investigation. Overall, a few interesting and ingenious approaches toward these ladder‐type heteroacenes have been proposed, reaching total yields in the region of 30 %. Finally, the optical, electrochemical, and other physicochemical properties are presented in the broader perspective of heteropentalenes. The parent 1,4‐dihydro‐pyrrolo[3,2‐b]pyrroles constitute the most electron‐rich, simple, aromatic heterocycles, and their simple derivatives and π‐expanded analogues possess strong violet, blue, or green fluorescence both in solution and in the solid state.     

Gold(III) Chloride Catalyzed Synthesis of Chiral Substituted 3‐Formyl Furans from Carbohydrates: Application in the Synthesis of 1,5‐Dicarbonyl Derivatives and Furo[3,2‐c]pyridine

This report describes a gold(III)‐catalyzed efficient general route to densely substituted chiral 3‐formyl furans under extremely mild conditions from suitably protected 5‐(1‐alkynyl)‐2,3‐dihydropyran‐4‐one using H₂O as a nucleophile. The reaction proceeds through the initial formation of an activated alkyne–gold(III) complex intermediate, followed by either a domino nucleophilic attack/anti‐endo‐dig cyclization, or the formation of a cyclic oxonium ion with subsequent attack by H₂O. To confirm the proposed mechanistic pathway, we employed MeOH as a nucleophile instead of H₂O to result in a substituted furo[3,2‐c]pyran derivative, as anticipated. The similar furo[3,2‐c]pyran skeleton with a hybrid carbohydrate–furan derivative has also been achieved through pyridinium dichromate (PDC) oxidation of a substituted chiral 3‐formyl furan. The corresponding protected 5‐(1‐alkynyl)‐2,3‐dihydropyran‐4‐one can be synthesized from the monosaccharides (both hexoses and pentose) following oxidation, iodination, and Sonogashira coupling sequences. Furthermore, to demonstrate the potentiality of chiral 3‐formyl furan derivatives, a TiBr₄‐catalyzed reaction of these derivatives has been shown to offer efficient access to 1,5‐dicarbonyl compounds, which on treatment with NH₄OAc in slightly acidic conditions afforded substituted furo[3,2‐c]pyridine.     

Cationic and mesoionic 1,3‐thiazolo‐[3,2‐c]quinazoline derivatives

4‐Allylthio‐2‐arylquinazolines 4a–c undergo cyclization by action of bromine to furnish 5‐aryl‐3‐bromomethyl‐2,3‐dihydrothiazolo[3,2‐c]quinazolin‐4‐ium bromides 5a–c . Compounds 5a–c undergo ring opening by action of water under acid catalysis to afford the corresponding dibromide derivatives 6a–c . Bromination of 3‐allyl‐2‐aryl‐4(3H)quinazolinethiones 7a–c leads to 5‐aryl‐2‐bromomethyl‐2,3‐dihydrothiazolo[3,2‐c]quinazolin‐4‐ium bromides 8a–c . However, anhydro‐3‐hydroxy‐5‐aryl‐1,3‐thiazolo[3,2‐c]quinazolin‐4‐ium hydroxide 10a–c were prepared by the cyclodehydration of the corresponding thioglycolic acids 9a–c with Ac₂O. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:576–580, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10148     

A one‐dimensional nickel(II) coordination polymer containing 2,6‐dipicolinate and dipyrido[3,2‐a:2′,3′‐c]phenazine

A new coordination polymer, catena‐poly[[(dipyrido[3,2‐a:2′,3′‐c]phenazine‐κ²N,N′)nickel(II)]‐μ‐2,6‐dipicolinato‐κ⁴O²,N,O⁶:O^2′], [Ni(C₇H₃NO₄)(C₁₈H₁₀N₄)]_n, exhibits a one‐dimensional structure in which 2,6‐dipicolinate acts as a bridging ligand interconnecting adjacent nickel(II) centers to form a chain structure. The asymmetric unit contains one Ni^II center, one dipyrido[3,2‐a:2′,3′‐c]phenazine ligand and one 2,6‐dipicolinate ligand. Each Ni^II center is six‐coordinated and surrounded by three N atoms and three O atoms from one dipyrido[3,2‐a:2′,3′‐c]phenazine ligand and two different 2,6‐dipicolinate ligands, leading to a distorted octahedral geometry. Adjacent chains are linked by π–π stacking interactions and weak interactions to form a three‐dimensional supramolecular network.     

An efficient conversion of catechols into 6H‐benzofuro[3,2‐c][1]‐benzopyran‐6‐one derivatives

Coupling of in‐situ generated o‐benzoquinones with 4‐hydroxycoumarin as a nucleophile has been studied in the presence of potassium ferricyanide as an oxidizing agent in aqueous solution. The results indicate that the quinones derived from catechols, participate in Michael addition reactions with 4‐hydroxycoumarin to form the 6H‐benzofuro[3,2‐c][1]benzopyran‐6‐one derivatives.     

Synthesis of new methylated thieno[2,3‐a] and [3,2‐b]carbazoles by reductive cyclization of 6‐(2′‐Nitrophenyl)benzo[b]thiophenes obtained by palladium‐catalyzed cross‐coupling isabel

The synthesis of new methylated thieno[2,3‐a] and [3,2‐b]carbazoles (5) (R=H) was achieved by a palladium‐catalyzed cross‐coupling, intramolecular reductive cyclization sequence of reactions. The cyclization precursors 6‐(2′‐nitrophenyl)benzo[b]thiophenes (3) were obtained by Suzuki cross‐coupling of 6‐boronated methylbenzo[b]thiophenes intermediates (2) with 2‐bromo or iodonitrobenzene. The boronated intermediates (2) were prepared via bromine‐lithium exchange followed by boron transmetalation and coupled in situ using Pd(OAc)₂ giving thus a “one‐pot” three steps reaction from the 6‐bromobenzo[b]thio‐phenes (1) to the cyclization precursors (3) . In the reductive cyclization step, N‐ethylthienocarbazoles (5) (R=Et) were also obtained. Several experiments have been made varying the amount of triethylphosphite and the time of reaction, to avoid their formation.