InCl3-catalyzed efficient one-pot synthesis of 2-pyrrolo-3′-yloxindoles

An InCl₃-catalyzed one-pot synthesis of 2-pyrrolo-3′-yloxindoles was achieved via three-component reaction of 3-phenacylideneoxindole, β-keto ester, and ammonium acetate at reflux by a sequential Michael addition followed by Paal-Knorr condensation.     

Synthesis, characterization and photophysical study of a series of neutral isocyano rhodium(I) complexes with pyridylindolide ligands

Pyridylindole ligand and its chloro substituted derivatives have been synthesized and incorporated into the square planar bis(phenylisocyano) rhodium(I) complexes to give a series of neutral rhodium(I) complexes with general formula of [Rh(X-pyind)(CNR)₂] (R = 2,6-(CH₃)₂-4-BrC₆H₂, 2,4-Cl₂-6-(CH₃O)C₆H₂, 2,4,6-Br₃C₆H₂, 2,4,6-Cl₃C₆H₂; L = 2-(2′-pyridyl)indole, 5-chloro-2-(2′-pyridyl)indole, 4,6-dichloro-2-(2′-pyridyl)indole). The structures of two complex precursors [Rh(cod)(Cl-pyind)] and [Rh(cod)(Cl₂pyind)], and the target complex [Rh(pyind)(CNC₆H₂-2,4-Cl₂-6-(OCH₃))₂] were determined by X-ray crystallography. The UV-vis absorption properties of these complexes and their responses towards the change of temperature were also investigated.     

A Simple Central Seven-Membered BOPYIN: Synthesis,Structural, Spectroscopic Properties,and Cellular Imaging Application

A two-step, one-flask synthesis of central seven-membered borondifluoride-3,3-dimethyl-2-[2-(2-pyrrolyl)ethenyl] indole (BOPYIN) ligands has been developed by using the unexplored 3,3-dimethyl-2-[2-(2-pyrrolyl)ethenyl] indole. The simple synthetic approach has enabled modification of the electronic structure by changing the substituents on the indole unit. X-ray analysis indicated that conformations of the seven-membered BF₂ complex including BOPYIN and diazaborepin differ from that of the five- and six-membered organoboron complexes. Interestingly, the bond angle of the N⋅⋅⋅B−N bond increases with the number of atoms in the core ring, based on Baeyer strain theory. These unsymmetric BOPYIN derivatives have excellent photophysical properties, including high fluorescence quantum yields, except for BOPYIN- 4 in the solution state, large Stokes shifts, and good molar absorptivity. The dipole moment of BOPYIN- 3 in the first excited singlet state and ground state was demonstrated by a linear Lippert–Mataga plot. The absorption and emission spectra were not mirror images for BOPYIN- 1 – 3 and 5 , in contradiction to Kasha's rule, as determined by TDDFT. The synthesized BOPYINs have been shown to be biocompatible fluorophores in cell bioimaging.     

Synthesis of macroheterocyclic compounds on the basis of 3-chloro-2-hydrazinoquinoxaline

2-Amino-1-[(3-chloro-2-quinoxalinyl)azo]naphthalene was obtained by oxidative coupling of 3-chloro-2-hydrazinoquinoxaline with 2-aminonaphthalenesulfonic acid; cross self-cyclization of the product was used to synthesize macrocyclic compounds, viz., [1,2,5,8,9,12]hexaazacyclotetradecene derivatives. 4-[(3-Chloro-2-quinoxalinyl)azo]-5-chloro-3-methyl-1-phenylpyrazole was obtained by the reaction of the 4-(3-chloro-2-quinoxalinyl)hydrazone of 2,4-dihydro-5-methyl-2-phenyl-3H-pyrazole-3,4-dione with POCl₃. Reaction of this product with 2,2-diaminoazobenzene under standard conditions gave [1,2,5,8,9,12]-hexaazacyclotetradecene derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 546–551, April, 1981.     

A simple one-pot synthesis of functionalised 6-(indol-3-yl)-2,2′-bipyridine derivatives via multi-component reaction under neat condition

A series of 4-aryl-6-(1H-indol-3-yl)-2,2-bipyridine-5-carbonitrile derivatives were synthesized via a one-pot multi-component reaction of aromatic aldehydes, 3-(cyanoacetyl)indole and 2-acetyl pyridine in ammonium acetate by conventional heating and microwave irradiation under solvent-free condition. Also a series of 6,6′-di(1H-indol-3-yl)-4,4′-diaryl-2,2′-bipyridine-5,5′-dicarbonitrile derivatives were synthesized using cinnamils, 3-(cyanoacetyl)indole and ammonium acetate. The methodology affords high yields of product at short reaction time.     

Synthesis of indole alkaloid analogues containing the novel hexahydropyrrolo[1′,2′,3′:1,9a,9]imidazo[1,2-a]indole skeleton by ring-closing reactions of tryptophan-derived α-amino nitriles

New indole alkaloid analogues, containing a 10b-methyl- or a 10b-hydroxy-1,2,4,5,10b,10c-hexahydropyrrolo[1′,2′,3′:1,9a,9]imidazo[1,2-a]indole skeleton, have been obtained by highly stereoselective electrophile addition-cyclization reactions of a tryptophan-derived α-amino nitriles.     

Synthesis and electrochemical characterization of dipyrroles separated by diphenyleneoxide and diphenylenesulfide spacers via the Trofimov reaction

4,4′-Bis[2-(1-vinylpyrrolyl)]diphenyloxide, 4,4′-bis(2-pyrrolyl)diphenylsulfide, 4-(2-pyrrolyl)-4′-[2-(1-vinylpyrrolyl)]diphenylsulfide and 4,4′-bis[2-(1-vinylpyrrolyl)]diphenylsulfide have been synthesized in a one-pot procedure from oximes of corresponding diacetylphenylenoxide and -sulfide through their reaction with acetylene in the MOH-DMSO systems (M=Li, K) at 80-130 °C under pressure of 10-15 atm, thus illustrating applicability and general character of the reaction of synthesis of diverse dipyrrole-phenylene assemblies and their N-vinyl derivatives. Two of the pipyrroles are promising for creating new conducting polymers with sulfur and oxygen atoms in the conjugation chain and for the study of the influence of the diphenyleneheteroatom moiety on conductivity of final polymer products. For the dipyrroles with the diphenyleneheteroatom moieties and 1,4-phenylene spacer the luminescence characteristics were determined.     

Fluorination in superacids: a novel access to biologically active compounds

In HF-SbF₅, reaction of various alkaloids with NBS, NCS, H₂O₂ yields fluoroderivatives: anti-addition is observed at the C6C7 double bond with tabersonine, but a more complex reaction is operative with vindoline, leading to 7-substituted (Br, Cl, OH)-20-fluoro derivatives. A completely different reaction pathway is observed with bis indole alkaloids (vinblastine, anhydrovinblastine, vinorelbine) in HF-SbF₅. In the presence of NBS (or better of CCl₄ or CHCl₃), 20′,20′-difluoroderivatives are obtained. Vinflunine (20′,20′-difluoro-3′,4′-dihydrovinorelbine) has been selected for its promising antitumor activity.     

Pyrazolo[2′,3′:3,4][1,3]oxazino[5,6-b]quinoxaline, a novel tetracyclic ring system

Reaction of 2-chloro-3-(3-chloro-1H-pyrazol-5-yl)quinoxaline and aldehydes does not afford the corresponding N-(α-hydroxyalkylated) derivatives but results in a cyclisation reaction to give a derivative bearing the hitherto undescribed pyrazolo[2′,3′:3,4][1,3]oxazino[5,6-b]quinoxaline system.     

Toward poly(aminophthalimide), structures of dimers and trimers

Poly(aminophthalimide) (PAP) dimers and trimers have been synthesized by palladium-catalyzed cross-coupling reactions of 3-aminophthalimides with 3-chloro- and 3,6-dichlorophthalimide, respectively. When Pd(OAc)₂, XPhos (2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl), and K₃PO₄ are used, the C-N bond-forming reactions proceed quantitatively. The structures of those oligomers are examined by experimental and theoretical techniques including NMR, IR, single-crystal X-ray diffraction, and DFT calculations. The strong preference for cisoid structure of the diphthalimidylamine unit bearing a bifurcate hydrogen bonding is disclosed. Therefore, the aminophthalimide backbone is a highly promising candidate for the construction of a dynamically ordered helical structure.     

Diastereoselective synthesis of trisubstituted piperidines: a versatile synthon for elaboration of uncommon poly(aza)heterocyclic structures

Hetero Michael addition on chiral β′-amino-α,β-unsaturated ketone furnished, after some structural modifications, β,β′-diaminoketals. Mannich type reaction of these diamines with an aldehyde led, with a high diastereoselectivity, to trisubstituted piperidines. Starting from a functionalized aldehyde and after subsequent deprotection of the amino group, an intramolecular Michael addition provided octahydro-2H-pyrrolo-[3,4-b]-pyridine, an uncommon framework found in compounds exhibiting biological activity.     

Regioselective Opening of Chalcone Epoxides with Nitrogen Heterocycles Using Indium(III) Chloride as an Efficient Catalyst

Indium(III) chloride catalyzes regioselective ring opening of chalcone epoxides with nitrogen heterocycles such as indole, 2-methyl indole, and pyrrole under mild conditions at room temperature to afford 1,3-diaryl-2-hydroxy-3-(1H-3-indolyl/2-pyrrolyl)propan-1-ones in good yields (60–88%) within 20–50 min.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

Synthesis and properties of indolo-3,3′-trimethinecyanines substituted in the polymethine chain and heterorings

New 8-chloro-, 9-cyano-, and 8-methyl-9-carboxy-substituted (in the outer polymethine chain), indolo-3,3-trimethinecyanines containing substituents in the 2, 5, or 7 position of the indole heteroresidues were synthesized, and their spectral, polarographic, and photographic properties were studied. It is shown that electron-acceptor substituents in the 2 and 2 positions of the indole heteroresidues and the 8 and/or 9 positions of the polymethine chain of the dye molecules that do not have steric hindrance give rise to a bathochromic shift of their absorption maxima. 8-Chloro-, 9-cyano- and 8-methyl-9-carbethoxyindolo-3,3-trimethinecyanines with electron-acceptor groups in the 2 and 2 positions are ineffective sensitizers of direct positive silver halide emulsions.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 897–901, July, 1988.     

2-Polyfluoroalkylchromones. 14. Synthesis of 4-chloro-3(5)-(2-hydroxyaryl)-5(3)-polyfluoroalkylpyrazoles

3-Chloro-2-polyfluoroalkyl- and 3-chloro-6-nitro-2-polyfluoroalkylchromones were synthesized. These compounds react with N₂H₄·2HCl on boiling in ethanol to form 4-chloro-3(5)-(2-hydroxyaryl)-5(3)-polyfluoroalkylpyrazoles.     

Michael reaction of indoles with 3-(2′-nitrovinyl)indole under solvent-free conditions and in solution. An efficient synthesis of 2,2-bis(indolyl)nitroethanes and studies on their reduction

Michael reaction of 3-(2′-nitrovinyl)indole with eight 3-unsubstituted indoles on TLC-grade silica gel furnished unsymmetrical bis(indolyl)nitroethanes in 7-12 min under microwave irradiation and in 8-14 h at rt. In contrast, the p-TsOH-catalysed reaction of the nitrovinylindole with the 3-unsubstituted and two 3-substituted indoles in solution under reflux furnished both unsymmetrical and symmetrical bis(indolyl)nitroethanes, the latter resulting from novel tandem Michael addition-elimination-Michael addition reactions. The synthesis of a 2′,3″-bis(indolyl)nitroethane, the precursor core structure of two bioactive marine metabolites, and the reduction of 2,2-bis(3′-indolyl)nitroethane to the corresponding ethylamine, isolated as its N-acetyl derivative, have been achieved. Significantly, attempted hydrolysis of three nitronates, derived from the corresponding bis(indolyl)nitroethanes, with buffered aqueous TiCl₃ has led to the first isolation of oximes (syn/anti-mixture) as the only products.     

Synthesis of symmetrical and unsymmetrical diindolylmethanes via acid-catalysed electrophilic substitution reactions

A range of activated indole-2-carboxylate derivatives was prepared via the Hemetsberger indole synthesis. Vilsmeier formylation was explored to establish regioselectivity and to prepare a range of new indole carbaldehydes. The indole aldehydes were reduced to the corresponding hydroxymethylindoles in good yields by the use of sodium borohydride in THF. Symmetrical 4,4′-, 6,6′- and 7,7′-diindolylmethanes were prepared via the acid-catalysed reaction of the corresponding hydroxymethylindoles. Furthermore, the treatment of methyl 4-hydroxymethyl-5,6-dimethoxyindole-2-carboxylate and a range of methyl indole esters with acetic acid led to the formation of unsymmetrical 4,6′- and 4,7′-dindolylmethanes.     

A concise synthesis of 3′-α-fluoro-2′,3′-dideoxyguanosine (FddG) via 3′-α-selective fluorination of 8,2′-thioanhydronucleoside

The antiviral nucleoside 3′-α-fluoro-2′,3′-dideoxyguanosine (FddG) was synthesized via 3′-α-selective fluorination of 8,2′-thioanhydronucleoside as the key step. Desulfurization of 3′-α-fluoro-3′-deoxy-8,2′-thioanhydronucleoside could be achieved by the treatment with Raney Ni in toluene. This method provides a concise route to 3′-α-fluoro-2′,3′-dideoxynucleosides that avoids the use of explosive and expensive SF₄-related fluorinating reagents.     

Ruthenium-catalyzed cyclization of 3-en-1-ynyl imines with nucleophiles via tandem 5-exo-dig cyclization and nucleophilic addition

Treatment of 3-en-1-ynyl imines with TpRuPPh₃(CH₃CN)₂PF₆ catalyst (1 mol %) in DCE (50 °C, 6 h) effected catalytic cyclization with suitable nucleophiles and gave functionalized pyrroles in good yields. The reaction mechanism is proposed to proceed via (2-pyrrolyl)carbenoid intermediates derived from 5-exo-dig cyclization. This catalytic reaction works well with various nucleophiles, including water, alcohols and anilines.     

Stereoselective SN2′ alkylation reaction sequence of the γ,δ-epoxy α,β-unsaturated ester system via γ,δ-chlorohydrin intermediates by the use of a R3Al-CuCN reagent

A novel stereoselective S_N2′ alkylation reaction sequence of the γ,δ-epoxy α,β-unsaturated ester system has been developed which involves a regioselective substitution reaction with chloride ions at the γ-position and a subsequent S_N2′ alkylation reaction of the resulting γ-chloro-δ-hydroxy derivatives with a R₃Al-CuCN reagent. The new methodology was demonstrated to be applicable to a variety of substrates and to provide various δ-hydroxy-α-alkyl-β,γ-unsaturated esters including those bearing a quaternary asymmetric carbon atom at the α-position in a highly stereoselective manner and high yields.